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991.
Phosphonopeptides as Antibacterial Agents: Rationale, Chemistry, and Structure-Activity Relationships 总被引:2,自引:1,他引:1 下载免费PDF全文
Frank R. Atherton Michael J. Hali Cedric H. Hassall Robert W. Lambert Peter S. Ringrose 《Antimicrobial agents and chemotherapy》1979,15(5):677-683
Peptide mimetics with C-terminal residues simulating natural amino acids have been designed as inhibitors of bacterial cell wall biosynthesis. The phosphonopeptide series consisting of various l and d residues of natural amino acids combined with 1-aminoalkyl (and aryl-alkyl-) phosphonic acid residues had the most interesting antibacterial properties when the C-terminal residue was l-1-aminoethylphosphonic acid. The in vitro antibacterial activities of representative phosphonodi- to phosphonohexapeptides were investigated. The antibacterial action of the active compounds has been explained in terms of transport into the bacterial cell and intracellular release of the alanine mimetic, which interferes with the biosynthesis of the peptidoglycan of the bacterial cell wall. 相似文献
992.
Spooren W Mombereau C Maco M Gill R Kemp JA Ozmen L Nakanishi S Higgins GA 《Psychopharmacology》2004,175(1):99-105
Rationale Glutamate signalling through the N-methyl-d-aspartate (NMDA) receptor is of critical importance for normal central nervous system (CNS) function, as indicated by the marked behavioural disturbances produced by non-subtype selective NMDA antagonists such as dizocilpine (MK-801).Objective The present studies were designed to investigate the involvement of the two major NMDA receptor subunits in the central nervous system, i.e. NR2A and NR2B, on sensorimotor gating in mice.Methods These experiments utilised the non-subtype-selective NMDA antagonist dizocilpine, a line of NR2A-KO mice and the selective NR2B antagonist Ro 63–1908, in the study of pre-pulse inhibition of the startle response (PPI).Results The non-selective NMDA receptor antagonist dizocilpine (0.1–1 mg/kg, IP) robustly disrupted PPI in wild-type mice. Conversely, selective genetic or pharmacological inhibition of either the NMDA NR2A or NR2B receptor subunit containing receptors, respectively, had no effect on PPI. Thus, NR2A KO mice showed normal PPI compared with wild-type littermate controls, and administration of Ro 63-1908 (1–10 mg/kg IP) to wild-type mice did not affect PPI. However, selective inhibition of NR2A and NR2B by administration of Ro 63–1908 to NR2A KO mice significantly disrupted PPI.Conclusions These data imply that concomitant inhibition of both NR2A and NR2B subunit-containing NMDA receptors is necessary to disrupt PPI, suggesting that inhibition of NR2A and NR2B-containing NMDA receptors is required to elicit behaviours suggestive of psychomimetic effects in man. 相似文献
993.
994.
Chen JM Le Maréchal C Lucas D Raguénès O Férec C 《Molecular genetics and metabolism》2003,79(1):67-70
Several genetic factors have been well known to predispose one to chronic pancreatitis (CP). However, little is known about the genetic factors that may provide a protective effect against the disease. Having found a nonsense mutation (c.111C>A; Y37X) and a splicing mutation (IVS2+1G>A) in the cationic trypsinogen gene (protease, serine, 1; PRSS1) in alcoholics without the development of CP, but not in alcoholics with CP and patients with hereditary or idiopathic CP, we propose that while "gain of function" mutations in the PRSS1 gene predispose one to pancreatitis, "loss of function" mutations in the gene may protect one against the disease. 相似文献
995.
996.
A pro-nociceptive role of neuromedin U in adult mice 总被引:4,自引:0,他引:4
Although the neuropeptide neuromedin U (NMU) was first isolated from the spinal cord, its actions in this site are unknown. The recent identification of the NMU receptor subtype 2 (NMU2R) in the spinal cord has increased the interest in investigating the role of NMU in this part of the central nervous system. Here, we report a novel function for NMU in spinal nociception in the mouse. Systemic perfusion of NMU (rat, NMU-23) dose-dependently (0.2, 0.5, 1, and 2.5 microM) potentiated both the background activity and noxious pinch-evoked response of nociceptive or wide dynamic range, but not non-nociceptive, dorsal horn neurons. At 2.5 microM, NMU-23 increased the total background activity from 154+/-34 to 1374+/-260 spikes/160 s (P<0.005, n=28) and increased the evoked nociceptive response by 185+/-50% (P<0.01, n=13). Intrathecal administration of NMU-23 (0.4, 1.1, and 3.8 nmol/10 microl) dose-dependently decreased thermal withdrawal latencies and produced a morphine-sensitive behavioral response. These electrophysiological and behavioral results suggest that NMU may be a novel physiological regulator in spinal nociceptive transmission and processing. 相似文献
997.
Dray X Boutron-Ruault MC Bertrais S Sapinho D Benhamiche-Bouvier AM Faivre J 《Gut》2003,52(6):868-873
BACKGROUND: Diet has been identified as a major determinant of colorectal cancer (CRC) but little is known of its influence on CRC survival. AIMS: To study the influence of dietary factors on survival in patients who had undergone potentially curative CRC surgery. PATIENTS: Among 171 patients included in a case control study of CRC aetiological factors, 10 year survival data on 148 patients who underwent resection of the tumour for potential cure were obtained from a Registry of Digestive Tumours. METHODS: Tertiles of food and nutrient intakes were entered into Cox proportional hazards survival models, controlling for age, sex, tumour stage, and tumour location. RESULTS: Only five year survival was influenced by the pre-diagnosis diet. High energy intake, as a result of high carbohydrate, protein, and lipid intake, was strongly related to increased survival. Five year relative risk of death for the highest versus the two lowest tertiles of energy intake was 0.18 (95% confidence interval 0.07; 0.44). This effect was similar in both sexes, for the colon and for the rectum. It was stronger in patients with N+/M+ tumours (relative risk 0.06) than in those with less advanced tumours (relative risk 0.37; stage-energy interaction term non-significant). No specific food or nutrient could be identified as having prognostic significance. CONCLUSIONS: Whether high energy intake selects less severe tumoral clones or modifies antitumoral immunity remains unclear. Larger series need to be investigated before conducting intervention studies but our findings should prompt nutritional follow up in CRC patients. 相似文献
998.
999.
Campos GM Oberg S Gastal O Theisen J Nigro JJ Hagen JA Costantini M Bremner CG DeMeester TR Crookes PF 《Digestive diseases and sciences》2003,48(6):1057-1061
The purpose of this study was to evaluate the interindividual and intraindividual variability of slow motorized pull-through lower esophageal sphincter (LES) manometry compared to standard station pull-through LES manometry to measure LES overall length, abdominal length, and pressure and to report normal values for the slow motorized pull-through method. The slow motorized pull-through had significantly smaller coefficient of variation, indicating closer agreement between different examiners in analyzing a given tracing. The correlation coefficients for each parameter in normal subjects and symptomatic patients was significantly higher when using slow motorized pull-through for both patients and normal subjects for all three parameters. The 5th percentile of normal values obtained from 41 volunteers for LES overall length, abdominal length, and pressure was 2.7 cm, 1.4 cm, 5.1 mm Hg, respectively. The results indicate that the slow motorized pull-through method is more reproducible than the standard station pull-through method both between different observers and when the same examiner measures the same tracing on two different occasions. 相似文献
1000.
BACKGROUND: Cyclophosphamide (CYP) is used to treat cancers in combination with mesna to prevent cystitis. The use of extemporaneously prepared admixtures of these drugs must be supported by documentation of their chemical stability.OBJECTIVE: To evaluate the chemical stability of CYP and mesna admixtures in dextrose 5% polyethylene infusion bags.METHODS: The drugs were diluted in 100-mL dextrose 5% infusion bags to final concentrations of CYP 10.8 mg/mL with mesna 3.2 mg/mL (solution A) and CYP 1.8 mg/mL with mesna 0.54 mg/mL (solution B). Six infusion bags from each solution were stored at 4 degrees C and 6 were stored at room temperature. Triplicate HPLC determinations were performed on each bag to measure drug concentrations at 0, 1, 2, 4, 6, 12, 24, 48, and 96 hours.RESULTS: At 96 hours, drug concentrations in all solutions stored at room temperature were found to be <80% compared with the initial concentrations. The solutions stored at 4 degrees C retained at least 90% of the initial drug concentrations at 48 hours. The pH of solutions A and B stored at room temperature decreased significantly by 4.44 and 4.31 units, respectively. The pH of the refrigerated infusion bags decreased significantly by 1.46 units for solution B.CONCLUSIONS: Admixtures stored at 4 degrees C (pH 7.90 +/- 0.004; mean +/- SD) are stable for 48 hours. The CYP and mesna combination can be infused at room temperature over 6 hours without significant degradation of the drugs. Stabilities are dependent on pH, temperature, and/or concentration. 相似文献