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排序方式: 共有536条查询结果,搜索用时 171 毫秒
101.
Crosby DC Lei X Gibbs CG McDougall BR Robinson WE Reinecke MG 《Journal of medicinal chemistry》2010,53(22):8161-8175
Fourteen analogues of the anti-HIV-1 integrase (IN) inhibitor L-chicoric acid (L-CA) were prepared. Their IC(50) values for 3'-end processing and strand transfer against recombinant HIV-1 IN were determined in vitro, and their cell toxicities and EC(50) against HIV-1 were measured in cells (ex vivo). Compounds 1-6 are catechol/β-diketoacid hybrids, the majority of which exhibit submicromolar potency against 3'-end processing and strand transfer, though only with modest antiviral activities. Compounds 7-10 are L-CA/p-fluorobenzylpyrroloyl hybrids, several of which were more potent against strand transfer than 3'-end processing, a phenomenon previously attributed to the β-diketo acid pharmacophore. Compounds 11-14 are tetrazole bioisosteres of L-CA and its analogues, whose in vitro potencies were comparable to L-CA but with enhanced antiviral potency. The trihydroxyphenyl analogue 14 was 30-fold more potent than L-CA at relatively nontoxic concentrations. These data indicate that L-CA analogues are attractive candidates for development into clinically relevant inhibitors of HIV-1 IN. 相似文献
102.
Robert R. Luedtke Rebekah A. Freeman Michael W. Martin J.W. Bastien J. Zalles-Asin Manfred G. Reinecke 《Pharmaceutical biology》2013,51(4):315-325
Nearly 100 aqueous, organic and alcoholic extracts of 46 Bolivian, Chinese and Indian medicinal plants were evaluated for their ability to stimulate adenylyl cyclase using Sf9 cells expressing rat D1a dopamine receptors in a broken cell assay. The aqueous extract of Cestrum parqui, a Bolivian plant of the Solanaceae, stimulated adenylyl cyclase in Sf9 cells expressing either rat D1a or rat D1b receptors, but no stimulation was observed in uninfected Sf9 cells. Flupenthixol, a nonselective dopaminergic antagonist, was found to attenuate both dopamine- and extract-dependent stimulation of adenylyl cyclase. The extract stimulated adenylyl cyclase in a concentration-dependent manner. However, adenylyl cyclase activity returned to basal levels at the highest concentration of extract that was tested. The extract was also evaluated for the ability to stimulate adenylyl cyclase in stably transfected HEK cells expressing human D1 receptors using a cAMP accumulation, whole cell assay. The extract stimulated HEK cells expressing human D1a dopamine receptors, but no enzyme stimulation was observed in untransfected HEK cells. Studies using transfected HEK cells expressing D2 receptors indicate that this extract also has intrinsic activity at D2 dopamine receptor. These studies suggest that this plant extract contains a component that is an agonist at dopamine receptors. 相似文献
103.
Baumeister J Reinecke K Liesen H Weiss M 《European journal of applied physiology》2008,104(4):625-631
A skilled player in goal-directed sports performance has the ability to process internal and external information in an effective
manner and decide which pieces of information are important and which are irrelevant. Focused attention and somatosensory
information processing play a crucial role in this process. Electroencephalographic (EEG) recordings are able to demonstrate
cortical changes in conjunction with this concept and were examined during a golf putting performance in an expert-novice
paradigm. The success in putting (score) and performance-related cortical activity were recorded with an EEG during a 5 ×
4 min putting series. Subjects were asked to putt balls for four min at their own pace. The EEG data was divided into different
frequencies: Theta (4.75–6.75 Hz), Alpha-1 (7–9.5 Hz), Alpha-2 (9.75–12.5 Hz) and Beta-1 (12.75–18.5 Hz) and performance related
power values were calculated. Statistical analysis shows significant better performance in the expert golfers (P < 0.001). This was associated with higher fronto-midline Theta power (P < 0.05) and higher parietal Alpha-2 power values (P < 0.05) compared to the novices in golf putting. Frontal Theta and parietal Alpha-2 spectral power in the ongoing EEG demonstrate
differences due to skill level. Furthermore the findings suggest that with increasing skill level, golfers have developed
task solving strategies including focussed attention and an economy in parietal sensory information processing which lead
to more successful performance. In a theoretical framework both cortical parameters may play a role in the concept of the
working memory. 相似文献
104.
We summarize and integrate research on cognitive vulnerability to depression among children and adolescents. We first review prospective longitudinal studies of the most researched cognitive vulnerability factors (attributional style, dysfunctional attitudes, and self-perception) and depression among youth. We next review research on information processing biases in youth. We propose that the integration of these two literatures will result in a more adequate test of cognitive vulnerability models. Last, we outline a program of research addressing methodological, statistical, and scientific limitations in the cognitive vulnerability literature. 相似文献
105.
106.
Reinecke J Koch H Meijer H Granrath M Schulitz KP Wehling P 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》1999,11(2):103-114
Despite the high prevalence of the disease, at present little effective pharmacological treatment of rheumatoid arthritis is available. Novel approaches utilising biological agents have resulted in the development of new antiarthritic and antiinflammatory agents, such as tumour necrosis factor-alpha (TNFalpha)-specific antibodies and interleukin-1 receptor antagonist (IL-1ra). Local gene therapy not only allows the pharmaceutical use of these biologicals, but also allows for continuous drug supply, which is necessary for chronic diseases like rheumatoid arthritis. We discuss the basics of rheumatoid arthritis therapy, candidate genes and possible gene transfer methods. A current clinical gene therapy trial is focusing on the IL-1 system using IL-1ra as a transgene. The transfer system, clinical protocol and preliminary results are described. After treatment of 11 patients we feel that gene therapy will offer potential as a new avenue to treat rheumatoid arthritis. 相似文献
107.
Robey TE Saiget MK Reinecke H Murry CE 《Journal of molecular and cellular cardiology》2008,45(4):567-581
Stem cell transplantation may repair the injured heart, but tissue regeneration is limited by death of transplanted cells. Most cell death occurs in the first few days post-transplantation, likely from a combination of ischemia, anoikis and inflammation. Interventions known to enhance transplanted cell survival include heat shock, over-expressing anti-apoptotic proteins, free radical scavengers, anti-inflammatory therapy and co-delivery of extracellular matrix molecules. Combinatorial use of such interventions markedly enhances graft cell survival, but death still remains a significant problem. We review these challenges to cardiac cell transplantation and present an approach to systematically address them.Most anti-death studies use histology to assess engraftment, which is time- and labor-intensive. To increase throughput, we developed two biochemical approaches to follow graft viability in the mouse heart. The first relies on LacZ enzymatic activity to track genetically modified cells, and the second quantifies human genomic DNA content using repetitive Alu sequences. Both show linear relationships between input cell number and biochemical signal, but require correction for the time lag between cell death and loss of signal. Once optimized, they permit detection of as few as 1 graft cell in 40,000 host cells. Pro-survival effects measured biochemically at three days predict long-term histological engraftment benefits. These methods permitted identification of carbamylated erythropoietin (CEPO) as a pro-survival factor for human embryonic stem cell-derived cardiomyocyte grafts. CEPO's effects were additive to heat shock, implying independent survival pathways. This system should permit combinatorial approaches to enhance graft viability in a fraction of the time required for conventional histology. 相似文献
108.
Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries. 总被引:13,自引:0,他引:13
M Erren H Reinecke R Junker M Fobker H Schulte J O Schurek J Kropf S Kerber G Breithardt G Assmann P Cullen 《Arteriosclerosis, thrombosis, and vascular biology》1999,19(10):2355-2363
Plasma concentration of markers of inflammation are increased in patients with atherosclerosis. However, it is unclear whether the pattern and magnitude of this increase vary with the site and extent of disease. In 147 patients undergoing semiquantitative coronary angiography, we measured the acute-phase reactants C-reactive protein (CRP) or serum amyloid A (SAA); the proinflammatory cytokine interleukin 6 (IL-6); the active and total fractions of the anti-inflammatory cytokine transforming growth factor-beta (TGF-beta); the macrophage activation marker neopterin; and the infection marker procalcitonin. Compared with 62 patients without either coronary artery disease (CAD) or peripheral artery disease (PAD), 57 patients with CAD but no PAD showed greater median CRP (0. 4 versus 0.2 mg/dL, P=0.004) and IL-6 (3.8 versus 1.6 pg/mL, P=0. 007) levels and a lower level of active-TGF-beta (57 versus 100 ng/mL, P=0.038). Moreover, CRP, IL-6, and neopterin levels showed a positive and the active TGF-beta level a negative correlation with the extent of coronary atherosclerosis. Compared with these 57 patients with CAD alone, 15 patients with PAD and CAD had higher median levels of SAA (17 versus 7 mg/mL, P=0.008), IL-6 (12 versus 4 pg/mL, P=0.002), neopterin (14 versus 11 mg/dL, P=0.006), and total TGF-beta (11834 versus 6417 ng/L, P=0.001). However, these strong univariate associations of markers of inflammation and atherosclerosis were lost in multivariate analysis once age, sex, and high density lipoprotein cholesterol or fibrinogen were taken into account. Increased plasma levels of CRP, SAA, IL-6, TGF-beta, neopterin, and procalcitonin constitute an inflammatory signature of advanced atherosclerosis and are correlated with the extent of disease but do not provide discriminatory diagnostic power over and above established risk factors. 相似文献
109.
The modification of PVC with 4-mercaptopyridine is described. The content of pyridine groups in the products is measured by NMR and IR spectroscopy. The degree of modification depends on the reaction conditions, and values of up to 70% are achieved without degradation or other appreciable side reactions. The tertiary amino groups in the polymer can be alkylated with iodides of varying chain length to form quantitatively quaternary pyridinium salt groups, leading to PVC ionomers and polyelectrolytes. 相似文献
110.
Tschöpe C Seidl U Reinecke A Riester U Graf K Schultheiss HP Hilgenfeldt U Unger T 《International immunopharmacology》2003,3(3):335-344
The present study examined non-insulin-treated streptozotocin (STZ)-induced diabetic rats to determine the role of kinins in diabetic nephropathy. Their involvement in the renoprotective effect of the angiotensin-converting enzyme inhibitor (ACEI) ramipril was investigated using the bradykinin (BK) B(2)-receptor antagonist, icatibant (HOE 140), or a combination of the two drugs.Although, none of the treatments prevented the decline of the glomerular filtration rate (GFR) in diabetic rats, ramipril (3 mg/kg/day), but not icatibant (HOE 140; 500 microg/kg/day), prevented proteinuria in these animals. However, the antiproteinuric effect of ramipril was reduced by 45% when combined with icatibant. To explore whether the renal kallikrein-kinin system (KKS) belongs to the underlying mechanisms of these findings, we also determined urinary BK levels, renal kallikrein (KLK) and angiotensin-converting enzyme (ACE) activity as well as renal cortical mRNA levels of neutral endopeptidase 24.11 (NEP) and low-molecular weight (LMW) kininogen. STZ led to a reduction of renal KLK and ACE activity and NEP expression and to a three-fold increase of urinary BK excretion and renal kininogen expression. Icatibant given alone had no effect on these parameters. In contrast, ramipril treatment normalized urinary protein and BK excretion as well as kininogen mRNA expression without affecting NEP mRNA expression or KLK and ACE activity.Our data demonstrate that renal BK is increased in severe STZ-induced diabetes mellitus, but may affect glomerular regulation only to a minor degree under this condition. However, kinins are partly involved in the antiproteinuric action of ACEI at this stage of diabetic nephropathy. 相似文献