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排序方式: 共有699条查询结果,搜索用时 15 毫秒
61.
Mabley JG Pacher P Liaudet L Soriano FG Haskó G Marton A Szabo C Salzman AL 《American journal of physiology. Gastrointestinal and liver physiology》2003,284(1):G138-G144
Inosine, a naturally occurring purine formed from the breakdown of adenosine, has recently been shown to exert powerful anti-inflammatory effects both in vivo and in vitro. This study evaluated inosine as a potential therapy for colitis. Colitis was induced in mice by the administration of dextran sulfate sodium (DSS). Oral treatment with inosine was begun either before the onset of colitis or as a posttreatment once colitis was established. Evaluation of colon damage and inflammation was determined grossly (body wt, rectal bleeding), histologically, and biochemically (colon levels of MPO, MDA, and cytokines). DSS-induced colitis significantly increased inflammatory cell infiltration into the colon. DSS-induced colitis also increased colon levels of lipid peroxidation, cytokines, and chemokines. Inosine protected the colon from DSS-induced inflammatory cell infiltration and lipid peroxidation. Inosine also partially reduced these parameters in an experimental model of established colitis. Thus inosine treatment may be a potential therapy in colitis. 相似文献
62.
Low power millimeter wave irradiation exerts no harmful effect on human keratinocytes in vitro 总被引:4,自引:0,他引:4
Szabo I Manning MR Radzievsky AA Wetzel MA Rogers TJ Ziskin MC 《Bioelectromagnetics》2003,24(3):165-173
Low power millimeter wave (LP-MW) irradiation has been successfully used in clinical practice as an independent and/or supplemental therapy in patients with various diseases. It is still not clear, however, whether exposed skin is directly affected by repeated LP-MW irradiation and whether cells of the epidermis can be activated by the absorbed energy. Keratinocytes, the most numerous component of the epidermis are believed to manifest functional responses to physical stimuli. In this study we analyzed whether LP-MW irradiation modulated the production of chemokines, including RANTES and IP-10 of keratinocytes in vitro. We also investigated whether LP-MW irradiation induces a heat stress reaction in keratinocytes, and stimulates heat shock protein 70 (Hsp70) production. Vital staining of keratinocytes with carboxyfluorescein succinimidyl ester and ethidium bromide was used to analyze the MW effect on the viability of adherent cells. In addition, we studied the effect of LP-MW irradiation on intercellular gap junctional communication in keratinocyte monolayers by Lucifer yellow dye transfer. We found no significant changes in constitutive RANTES and inducible IP-10 production following LP-MW irradiation. LP-MW exposure of keratinocyte monolayers did not alter Hsp70 production, unlike exposure to higher power MWs (HP-MW) or hyperthermia (43 degrees C; 1 h). LP-MW irradiation and hyperthermia did not alter the viability of adherent keratinocytes, while HP-MW irradiation induced cellular damage within the beam area. Finally, we found no alteration in the gap junctional intercellular communication of keratinocytes following LP-MW irradiation, which on the other hand, was significantly increased by hyperthermia. In summary, we detected no harmful effect of LP-MW irradiation on both keratinocyte function and structure in vitro, although these cells were sensitive to higher MW power that developed heat stress reaction and cellular damage. Our results provide further evidence that LP-MW irradiation does not induce evidence of skin inflammation or keratinocyte damage and that its clinical application appears to be safe. 相似文献
63.
Smith AJ van Helvoort A van Meer G Szabo K Welker E Szakacs G Varadi A Sarkadi B Borst P 《The Journal of biological chemistry》2000,275(31):23530-23539
The human MDR3 gene is a member of the multidrug resistance (MDR) gene family. The MDR3 P-glycoprotein is a transmembrane protein that translocates phosphatidylcholine. The MDR1 P-glycoprotein related transports cytotoxic drugs. Its overexpression can make cells resistant to a variety of drugs. Attempts to show that MDR3 P-glycoprotein can cause MDR have been unsuccessful thus far. Here, we report an increased directional transport of several MDR1 P-glycoprotein substrates, such as digoxin, paclitaxel, and vinblastine, through polarized monolayers of MDR3-transfected cells. Transport of other good MDR1 P-glycoprotein substrates, including cyclosporin A and dexamethasone, was not detectably increased. MDR3 P-glycoprotein-dependent transport of a short-chain phosphatidylcholine analog and drugs was inhibited by several MDR reversal agents and other drugs, indicating an interaction between these compounds and MDR3 P-gp. Insect cell membranes from Sf9 cells overexpressing MDR3 showed specific MgATP binding and a vanadate-dependent, N-ethylmaleimide-sensitive nucleotide trapping activity, visualized by covalent binding with [alpha-(32)P]8-azido-ATP. Nucleotide trapping was (nearly) abolished by paclitaxel, vinblastine, and the MDR reversal agents verapamil, cyclosporin A, and PSC 833. We conclude that MDR3 P-glycoprotein can bind and transport a subset of MDR1 P-glycoprotein substrates. The rate of MDR3 P-glycoprotein-mediated transport is low for most drugs, explaining why this protein is not detectably involved in multidrug resistance. It remains possible, however, that drug binding to MDR3 P-glycoprotein could adversely affect phospholipid or toxin secretion under conditions of stress (e.g. in pregnant heterozygotes with one MDR3 null allele). 相似文献
64.
65.
Nagykaldi Z Kem D Lazzara R Szabo B 《American journal of physiology. Heart and circulatory physiology》2000,279(3):H1329-H1337
We investigated the roles of beta(1)- and beta(2)-receptors (beta-AR) in adrenergic enhancement of L-type Ca(2+) current (I(CaL)) in canine ventricular myocytes. Isoproterenol and l-norepinephrine produced a monophasic and a biphasic concentration-I(CaL) relationship (CR), respectively. alpha(1)-AR inhibition with prazosin and beta(2)-AR stimulation with zinterol or l-epinephrine shifted the CR of l-norepinephrine leftward. Zinterol (50 nM) and l-epinephrine (10 nM), but not prazosin, altered the biphasic CR of l-norepinephrine to a monophasic CR. Zinterol and l-epinephrine applied after l-norepinephrine had no effect on I(CaL). beta(2)-AR inhibition with ICI-118551 reduced the E(max) of isoproterenol and l-norepinephrine by 60% and abolished the augmentation of l-norepinephrine by zinterol and l-epinephrine. Carbachol (100 nM) modestly reduced the I(CaL) response to beta(1)-AR stimulation but abolished the enhancement via beta(2)-AR. Zinterol augmented the enhancement of I(CaL) by forskolin, IBMX, and theophylline, but not in the presence of CGP-20712A. We conclude that selective beta(2)-AR stimulation does not increase I(CaL) but enhances adenylyl cyclase activity when stimulated via beta(1)-AR and with forskolin. beta(2)-AR activity preconditions adenylyl cyclase for beta(1)-AR stimulation. 相似文献
66.
67.
S.K. Chikagwa-Malunga A.T. Adesogan N.J. Szabo R.C. Littell S.C. Phatak S.C. Kim K.G. Arriola C.M. Huisden D.B. Dean N.A. Krueger 《Animal Feed Science and Technology》2009,148(2-4):107-123
Mucuna pruriens seeds have relatively high crude protein (CP) concentrations, but little is known about their potential to replace commonly used CP supplements in ruminant rations. The aim of this experiment was to determine effects of replacing soybean meal (SB) with Mucuna on the performance of lambs. Forty Rambouillet lambs (33.2 ± 5.73 kg) fed a basal diet of maize grain, cottonseed hulls and urea were randomly assigned to one of four supplements formulated by substituting 0 (SB), 330 (Lo), 670 (Med) or 1000 g/kg (Hi) of soybean meal with rolled Mucuna seeds. Lambs were housed individually in metabolic crates and allowed ad libitum access to isocaloric (metabolizable energy=11.7 MJ/kg dry matter, DM) and isonitrogenous (CP = 146 g/kg, DM) diets for 14 d of adaptation and 7 d of total fecal collection. Fecal egg counts and coccidian oocyst scores were determined on d 14. Dry matter intake (1.7 kg/d versus 1.5 kg/d; P<0.05), CP digestibility (774 g/kg versus 714 g/kg DM; P<0.05) and N retention (28.0 g/d versus 20.4 g/d; P<0.01) were higher and amylase-pretreated neutral detergent fiber digestibility (617 g/kg versus 686 g/kg DM) was lower (P<0.05) in sheep fed SB versus Mucuna diets. However, supplementary protein source did not affect rumen pH, blood urea N or glucose concentration, or fecal egg counts. Increasing the level of Mucuna supplementation increased (P<0.05) level and efficiency of microbial protein synthesis, ruminal fluid acidity, total volatile fatty acid concentration, decreased (P<0.05) coccidian oocyst scores, and tended (P<0.10) to increase N retention. Therefore, SB is a better supplement than Mucuna to support performance of lambs. Nevertheless, Mucuna seeds are a promising CP supplement for situations where cost or availability precludes use of SB in ruminant rations. 相似文献
68.
S.K. Chikagwa-Malunga A.T. Adesogan L.E. Sollenberger S.C. Phatak N.J. Szabo S.C. Kim C.M. Huisden R.C. Littell 《Animal Feed Science and Technology》2009,148(2-4):124-137
The harmful effects of the 3,4-dihydroxy-l-phenylalanine (l-dopa) in Mucuna pruriens (Velvet bean) seeds have limited its use as a protein supplement for monogastrics and humans. Little is known about the extent of metabolism of Mucuna l-dopa in ruminants or its accumulation in ruminant tissues consumed as food by humans. This study aimed to determine if replacing soybean meal (SB) with Mucuna increases concentrations of l-dopa in rumen fluid, blood and muscle tissue of lambs. Twenty-seven RM lambs (RM; initial body weight, BW = 33.8 ± 5.44 kg) and 12 Florida Native (FN; initial BW = 24.9 ± 8.63 kg) lambs were assigned to four treatments and fed a basal diet of coastal bermudagrass hay, corn grain, and liquid molasses for 42 (FN) or 49 days (RM) and then slaughtered. Dietary supplements were formulated by substituting 0 (SB), 330 (Lo), 670 (Med) or at least 1000 (Hi) g/kg of SB with rolled Mucuna seeds (l-dopa, 24 g/kg dry matter, DM). Body weight was measured weekly and carcass characteristics and concentrations of l-dopa in rumen fluid, blood and the sterno-mandibularis muscle were measured at slaughter when concentrations of blood urea N, glucose, haptoglobin and cerruloplasmin were also measured. Lambs fed SB had higher (P<0.05) average daily gain than those fed Mucuna (0.20 versus 0.15 kg/day for RM; 0.21 versus 0.14 kg/day for FN). However, concentrate protein source did not affect dressing and concentrations of blood urea N, or blood glucose. Feeding the Hi diet versus the SB diet did not increase concentrations of blood cerruloplasmin, or l-dopa or concentrations of l-dopa metabolites in blood. No l-dopa was found in the ruminal fluid of the lambs and l-dopa concentrations in the sterno-mandibularis muscle were low (i.e., <5 ng l-dopa/g), and unaffected (P>0.05) by diet. Ingested Mucuna l-dopa was extensively metabolized in lambs, and did not accumulate to toxic levels in muscle tissues. 相似文献
69.
Annina Kelloniemi Zoltan Szabo Raisa Serpi Juha N?p?nkangas Pauli Ohukainen Olli Tenhunen Leena Kaikkonen Elina Koivisto Zsolt Bagyura Risto Kerkel? Margret Leosdottir Thomas Hedner Olle Melander Heikki Ruskoaho Jaana Rys? 《PloS one》2015,10(6)
The phosphatase and actin regulator 1 (PHACTR1) locus is a very commonly identified hit in genome-wide association studies investigating coronary artery disease and myocardial infarction (MI). However, the function of PHACTR1 in the heart is still unknown. We characterized the mechanisms regulating Phactr1 expression in the heart, used adenoviral gene delivery to investigate the effects of Phactr1 on cardiac function, and analyzed the relationship between MI associated PHACTR1 allele and cardiac function in human subjects. Phactr1 mRNA and protein levels were markedly reduced (60%, P<0.01 and 90%, P<0.001, respectively) at 1 day after MI in rats. When the direct myocardial effects of Phactr1 were studied, the skeletal α-actin to cardiac α-actin isoform ratio was significantly higher (1.5-fold, P<0.05) at 3 days but 40% lower (P<0.05) at 2 weeks after adenovirus-mediated Phactr1 gene delivery into the anterior wall of the left ventricle. Similarly, the skeletal α-actin to cardiac α-actin ratio was lower at 2 weeks in infarcted hearts overexpressing Phactr1. In cultured neonatal cardiac myocytes, adenovirus-mediated Phactr1 overexpression for 48 hours markedly increased the skeletal α-actin to cardiac α-actin ratio, this being associated with an enhanced DNA binding activity of serum response factor. Phactr1 overexpression exerted no major effects on the expression of other cardiac genes or LV structure and function in normal and infarcted hearts during 2 weeks’ follow-up period. In human subjects, MI associated PHACTR1 allele was not associated significantly with cardiac function (n = 1550). Phactr1 seems to regulate the skeletal to cardiac α-actin isoform ratio. 相似文献
70.
Khakpay R Polster D Köles L Skorinkin A Szabo B Wirkner K Illes P 《Purinergic signalling》2010,6(3):349-359
Locus coeruleus (LC) neurons in a rat brain slice preparation were superfused with a Mg2+-free and bicuculline-containing external medium. Under these conditions, glutamatergic spontaneous excitatory postsynaptic
currents (sEPSCs) were recorded by means of the whole-cell patch-clamp method. ATP, as well as its structural analogue 2-methylthio
ATP (2-MeSATP), both caused transient inward currents, which were outlasted by an increase in the frequency but not the amplitude
of the sEPSCs. PPADS, but not suramin or reactive blue 2 counteracted both effects of 2-MeSATP. By contrast, α,β-methylene
ATP (α,β-meATP), UTP and BzATP did not cause an inward current response. Of these latter agonists, only BzATP slightly facilitated
the sEPSC amplitude and strongly potentiated its frequency. PPADS and Brilliant Blue G, as well as fluorocitric acid and aminoadipic
acid prevented the activity of BzATP. Furthermore, BzATP caused a similar facilitation of the miniature (m)EPSC (recorded
in the presence of tetrodotoxin) and sEPSC frequencies (recorded in its absence). Eventually, capsaicin augmented the frequency
of the sEPSCs in a capsazepine-, but not PPADS-antagonizable, manner. In conclusion, the stimulation of astrocytic P2X7 receptors
appears to lead to the outflow of a signalling molecule, which presynaptically increases the spontaneous release of glutamate
onto LC neurons from their afferent fibre tracts. It is suggested, that the two algogenic compounds ATP and capsaicin utilise
separate receptor systems to potentiate the release of glutamate and in consequence to increase the excitability of LC neurons. 相似文献