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排序方式: 共有8664条查询结果,搜索用时 31 毫秒
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Lorenzo Melani Richard Mills David Hassman Robert Lipetz Leslie Lipka Alexandre LeBeaut Ramachandran Suresh Pabak Mukhopadhyay Enrico Veltri 《European heart journal》2003,24(8):717-728
AIMS: To evaluate the efficacy and safety of ezetimibe 10 mg administered with pravastatin in patients with primary hypercholesterolemia. METHODS AND RESULTS: After dietary stabilization, 2-12 week screening/washout period, and 4-week, single-blind, placebo lead-in period, 538 patients with baseline LDL-C > or =3.8 to < or =6.5 mmol/l and TG < or =4.0 mmol/l were randomized to one of eight possible treatments administered daily for 12 weeks: ezetimibe 10mg; pravastatin 10, 20, or 40 mg; ezetimibe 10 mg plus pravastatin 10, 20, or 40 mg; or placebo. The primary efficacy endpoint was percent reduction in LDL-C from baseline to study endpoint for ezetimibe 10 mg plus pravastatin (pooled doses) compared to pravastatin alone (pooled doses) and ezetimibe alone. The combined use of ezetimibe and pravastatin resulted in significant incremental reductions in LDL-C and TG compared to pooled pravastatin alone (p<0.01). Coadministration therapy reduced LDL-C by 34-41%, TG by 21-23%, and increased HDL-C by 7.8-8.4%, depending on the dose of pravastatin. The combined regimen was well tolerated, with a safety profile similar to pravastatin alone and placebo. CONCLUSIONS: When coadministered with pravastatin, ezetimibe provided significant incremental reductions in LDL-C and TG and was well tolerated with a safety profile similar to pravastatin alone. 相似文献
33.
Rainaldi Giuseppe; Meneveri Raffaella; Mariani Laura; Ginelli Enrico; Moretti Arcangela; Vatteroni Lucia 《Mutagenesis》1996,11(4):401-404
Clone CSA7 is a CHEF18 hamster cell line that shows an increasedintracellular accumulation of dCTP. To localize the mutationsthat accumulate spontaneously in a functional gene of such amutator phenotype, independent CSA7 mutants of the hypoxanthineguaninephosphoribosyl transferase (hprt) gene were isolated and screenedby a polymerase chain reactionsingle strand conformationpolymorphism technique. Sixty-two percent of mutants produceddetectable changes of the strand migration profile and the mutationswere preferentially localized in the exons 3 (31%) and 6 (62%).The sequencing of such exons revealed that the rate of C baseincorporation was the major mutation pathway and that the Abase of a GGA sequence was the preferential site of misincorporation.
3To whom correspondence should be addressed 相似文献
34.
Desensitization of AMPA Receptors Limits the Amplitude of EPSPs and the Excitability of Motoneurons of the Rat Isolated Spinal Cord 总被引:2,自引:0,他引:2
Intracellular recording was used to study the effect of cyclothiazide, a selective blocker of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor desensitization, on lumbar motoneurons of the rat isolated spinal cord. Cyclothiazide (25 μM) enhanced the responses to AMPA in a tetrodotoxin-insensitive fashion, without affecting those produced by N -methyl-D-aspartate or γ-aminobutyric acid. Excitatory postsynaptic potentials (EPSPs) evoked by dorsal root stimulation were strongly potentiated in amplitude while paired-pulse depression (produced by applying pairs of pulses at 2 s interval) of the EPSP was decreased. In the presence of cyclothiazide the frequency of spontaneous synaptic events was greatly increased and network-driven bursting activity developed with eventual loss of electrical excitability. The present results suggest that pharmacological block of AMPA receptor desensitization led to strong excitation of motoneurons and indicate a physiological role of desensitization in protecting these nerve cells from overactivity. 相似文献
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We investigated the effects of 5-hydroxytryptamine (5-HT, serotonin) in striatal cholinergic interneurones with gramicidin-perforated whole-cell patch recordings. Bath-application of serotonin (30 μ m ) significantly and reversibly increased the spontaneous firing rate of 37/45 cholinergic interneurones tested. On average, in the presence of serotonin, firing rate was 273 ± 193% of control. Selective agonists of 5-HT1A , 5-HT3 , 5-HT4 and 5-HT7 receptors did not affect cholinergic interneurone firing, while the 5-HT2 receptor agonist α-methyl-5-HT (30 μ m ) mimicked the excitatory effects of serotonin. Consistently, the 5-HT2 receptor antagonist ketanserin (10 μ m ) fully blocked the excitatory effects of serotonin. Two prominent after-hyperpolarizations (AHPs), one of medium duration that was apamin-sensitive and followed individual spikes, and one that was slower and followed trains of spikes, were both strongly and reversibly reduced by serotonin; these effects were fully blocked by ketanserin. Conversely, the depolarizing sags observed during negative current injections and mediated by hyperpolarization-activated cationic currents were not affected. In the presence of apamin and tetrodotoxin, the slow AHP was strongly reduced by 5-HT, and fully abolished by the calcium channel blocker nickel. These results show that 5-HT exerts a powerful excitatory control on cholinergic interneurones via 5-HT2 receptors, by suppressing the AHPs associated with two distinct calcium-activated potassium currents. 相似文献
38.
Cipriano C Giacconi R Muzzioli M Gasparini N Orlando F Corradi A Cabassi E Mocchegiani E 《Mechanisms of ageing and development》2003,124(8-9):877-886
Because of its similarity to ageing in impaired immune efficiency 48 h after surgical procedures on young partially hepatectomised mice, partial hepatectomy/liver regeneration (pHx) provides a good model for the study of inflammation in ageing. In old age, high metallothionein (I+II) (MT) sequesters a substantial number of intracellular zinc ions consequently leading to low zinc ion bioavailability for an adequate immune response. Corticosterone and IL-6 affect MTmRNA induction in inflammation and after pHx against oxidative damage. The aim of this study was to investigate the role played by MT in conferring immune plasticity in ageing and in very old age using the pHx model. 48 h after their partial hepatectomy, the crude zinc balance was negative in young, old and very old mice coupled with increased MT, corticosterone, sIL-6R and IL-6. Concomitantly, Natural Killer (NK) cell activity and IL-2 production decreased. Complete restoration of the nutritional-endocrine-immune parameters occurred 15 days from the surgical procedures in young and very old mice, but not in old or transgenic mice overexpressing MT. A significant positive or inverse correlation among nutritional-endocrine-immune parameters exists in young and very old mice, but not in old mice during liver regeneration. Since MT also affects c-myc, the gene expression of c-myc declines from 48 h to days 7 and 15 after pHx in young and very old mice, but remains constantly high in old pHx mice for the same days. This circumstance leads to the appearance of tumours in the long run in old pHx mice and survival times that are shorter than old sham controls. Because complete remodelling also occurs in IL-6 and in sIL-6R in very old mice during liver regeneration, the pre-existing inflammation is not detrimental in very old age. As such, very old mice are still responsive to large inflammation, such as pHx, thanks to correct MT homeostasis. Correct MT homeostasis, via c-myc, is therefore pivotal in both suitable liver regeneration and in conferring immune plasticity with subsequent successful ageing. High MT plays an extremely harmful role in ageing: on one hand it lowers zinc ion bioavailability levels required for immune efficiency and on the other hand it increases c-myc expression. The combination of immune depression and enhanced c-myc, via high MT, may trigger the appearance of age-related degenerative diseases. 相似文献
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A case of somatostatin-producing pancreatic tumor associated with severe insulindependent diabetes mellitus and ketoacidotic
coma is reported. The tumor, a 10-cm expansile mass arising from the pancreatic tail of a 70-yr-old woman, was first detected
by ultrasonography, performed because of abdominal pain, and subsequently confirmed by computed tomography and fine-needle
tumor aspiration. Pathologic investigation showed a predominatly solid-trabecular structure with scattered microacini and
psammomatous bodies. A large proportion of tumor cells expressed somatostatin and/or calcitonin. Following resection of the
primary tumor and three peripancreatic lymph nodes with metastases, the patient recovered rapidly from her diabetic syndrome
and remained in substantially good health during a subsequent 8-yr follow-up period, without evidence of tumor recurrence. 相似文献