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排序方式: 共有1366条查询结果,搜索用时 46 毫秒
21.
Inger B. Schipper Paul Steendijk Robert J. M. Klautz Enno T. van der Velde Jan Baan 《Pflügers Archiv : European journal of physiology》1993,425(5-6):426-433
It has been shown that in the intact canine heart the left-ventricular end-systolic pressure/volume relation (ESPVR) depends on loading conditions: an increase in arterial vascular resistance causes a leftwards shift and a steeper slope of the ESPVR, suggesting an increased inotropic state. Our purpose was to investigate the possible contribution of the sympathetic nervous system to this load sensitivity of the ESPVR, using intact, but denervated, hearts with normal coronary perfusion and afterload. We used two types of loading intervention: venous volume infusion and gradual occlusion of the descending aorta. ESPVRs were obtained in six anaesthetized open-chest dogs, both before and after bilateral ablation of the stellate ganglia. To exclude the influence of heart rate changes, bilateral vagotomy was performed and the heart was paced. The absence of (unpaced) heart rate changes in response to pressure alterations was used to confirm total denervation. Left ventricular pressure was measured with a micromanometer and volume with a conductance catheter. ESPVRs were essentially linear and characterized by their slope (E
es) and volume intercept at 12 kPa (V
12). We found that E
es (P<0.0001) and V12 (P<0.05) were both significantly different during pressure and volume interventions (0.67±0.29 and 0.41±0.18 kPa/ml for E
es and 16.2±8.2 and 18.2±8.4ml for V12 respectively). Denervation did not significantly affect the parameters of the ESPVR obtained by either volume infusion or aortic occlusion. Two-way analysis of variance revealed no significant interactive effect between denervation and intervention, indicating that the sympathetic nervous system does not influence the load dependency of the ESPVR. The dP/dt
max: EDV relationship behaved similarly. These results suggest that load dependency is an intrinsic property of the myocardium. 相似文献
22.
L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns 总被引:8,自引:3,他引:8
Fransen E; D'Hooge R; Van Camp G; Verhoye M; Sijbers J; Reyniers E; Soriano P; Kamiguchi H; Willemsen R; Koekkoek SK; De Zeeuw CI; De Deyn PP; Van der Linden A; Lemmon V; Kooy RF; Willems PJ 《Human molecular genetics》1998,7(6):999-1009
L1 is a neural cell adhesion molecule mainly involved in axon guidance and
neuronal migration during brain development. Mutations in the human L1 gene
give rise to a complex clinical picture, with mental retardation,
neurologic abnormalities and a variable degree of hydrocephalus. Recently,
a transgenic mouse model with a targeted null mutation in the L1 gene was
generated. These knockout (KO) mice show hypoplasia of the corticospinal
tract. Here we have performed further studies of these KO mice including
magnetic resonance imaging of the brain, neuropathological analysis and
behavioral testing. The ventricular system was shown to be abnormal with
dilatation of the lateral ventricles and the 4th ventricle, and an altered
shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the
KO mice is hypoplastic. Their exploratory behavior is characterized by
stereotype peripheral circling reminiscent of that of rodents with induced
cerebellar lesions.
相似文献
23.
24.
Cytosolic glutathione S-transferases are a family of enzymes involved in the metabolism of drugs, toxins, carcinogens and also of anticancer drugs. Recent studies have indicated that glutathione S-transferases (GSTs) may play an important role in the resistance of cells to toxins and carcinogens but also to anticancer drugs. This report reviews the current literature concerning the role of glutathione S-transferases in anticancer drug resistance. Moreover, the significance of GST pi in carcinogenesis and its role as prognostic factor is discussed. 相似文献
25.
C J van Laarhoven M E Schipper T J van Vroonhoven H G Gooszen 《Nederlands tijdschrift voor geneeskunde》1999,143(13):662-666
Reconstructive surgery for ulcerative colitis and familial adenomatous polyposis nowadays usually takes the form of an ileoanal pouch, involving making a reservoir of the terminal portion of the ileum which subsequently is anastomosed to the anal canal. This method results in definite cure in many cases, but is associated with a morbidity of 15-30% and fails in 10%. A new surgical treatment includes complete removal of the affected large bowel mucosa, guaranteeing oroanal intestinal continuity, limiting complications and providing good function of the reservoir or of the new rectum. In creation of an ileoneorectal anastomosis, complete removal of the affected mucous membrane is followed by preparing a functional 'neorectum' by means of pedicle grafting of ileal mucous membrane on to the uncovered muscular wall of the rectum. This operation gave good results in a small-scale clinical trial. 相似文献
26.
目的: 研究1,25-二羟维生素D3 对结肠癌细胞系Caco-2 细胞中报告基因表达的作用,并探讨在报告载体pGL2 序列中存在潜在的抑制性维生素D应答元件(VDRE)的可能性。方法: 采用磷酸钙沉淀法将报告载体转染入Caco-2 细胞。Caco-2细胞经不同浓度1,25-二羟维生素D3 处理后测定细胞裂解液中表达的荧光素酶活性。结果: 应用pGL2 报告载体时,当用pSG5-VDR表达载体共转染后,1,25-二羟维生素D3显著地抑制Caco-2 细胞荧光素酶的表达(P< 0.05);而未使用该表达载体共转染则无抑制作用(P> 0.05)。应用pGL3 报告载体时,不同浓度的1,25-二羟维生素D3 对pLG3转染后Caco-2 细胞表达的荧光素酶活性均无显著抑制作用(P> 0.05),该作用不依赖是否存在有pSG5-VDR表达载体共转染。结论:1,25-二羟维生素D3 对报告载体PGL2 荧光素酶表达具有抑制作用,而对pGL3 则否;类似人类PTH基因中的潜在抑制性VDRE存在于报告载体pGL2,在pGL3 中该VDRE业已改变。 相似文献
27.
Hempel S Senn P Pakdaman F Schmid MK Suppiger M Schipper I 《Klinische Monatsbl?tter für Augenheilkunde》1999,215(5):298-304
PURPOSE: To study the systemic effects of topically applied 5% phenylephrine. To investigate intraoperative injection of epinephrine in the anterior chamber as an alternative. METHOD: 75 patients undergoing cataract surgery were randomized into three groups. In group 1, the pupil was dilated using topically 5% phenylephrine and 1% cyclopentolate, the patients blocked the lacrimal drainage system themselves by digital compression. Group 2 received the same drops, digital compression was performed by one of the investigators. In Group 3, no preoperative phenylephrine was used--instead, epinephrine 1:25,000 was injected in the anterior chamber at the beginning of surgery. Retrobulbar anesthesia was performed in a short narcosis with ketamine and propofol. RESULTS: Mean preoperative blood pressure values were higher than the day before. They fell during narcosis, to increase significantly after the injection of the local anesthetics. At the beginning of surgery they were back to prenarcotic values. Intraoperative blood pressure remained stable. Preoperative day values were found two hours postop. There was no significant difference in the circulatory behavior between the three groups. For mydriasis, intraoperative intracameral epinephrine was not as effective as preoperative phenylephrine. CONCLUSION: In normotonic or medically treated arterial hypertensive patients, preoperative mydriasis using 5% phenylephrine is safe--proceeding the way described above. Compression of the lacrimal drainage system can be performed by the patients effectively. Intraoperative intracameral epinephrine does not replace preoperative phenylephrine. 相似文献
28.
Absorption Enhancing Effect of Cyclodextrins on Intranasally Administered Insulin in Rats 总被引:4,自引:0,他引:4
Merkus Frans W. H. M. Verhoef J. Coos Romeijn Stefan G. Schipper Nicolaas G. M. 《Pharmaceutical research》1991,8(5):588-592
The absorption enhancing effect of -, -, and -cyclodextrin (CD), dimethyl--cyclodextrin (DMCD), and hydroxypropyl--cyclodextrin (HPCD) on intranasally administered insulin was investigated in rats. Coadministration of 5% (w/v) DMCD to the insulin solution resulted in a high bioavailability, 108.9 ± 36.4% (mean ± SD, n = 6), compared to i.v. administration, and a strong decrease in blood glucose levels, to 25% of their initial values. Coadministration of 5% -CD gave rise to an insulin bioavailability of 27.7 ± 11.5% (mean ± SD, n = 6) and a decrease in blood glucose to 50% of its initial value. The rate of insulin absorption and the concomitant hypoglycemic response were delayed for the -CD-containing solution as compared to the DMCD preparation. The other CDs, HPCD (5%), -CD (1.8%), and -CD (5%), did not have significant effects on nasal insulin absorption. DMCD at a concentration of 5% (w/v) induces ciliostasis as measured on chicken embryo tracheal tissue in vitro, but this effect is reversible. In conclusion, DMCD is a potent enhancer of nasal insulin absorption in rats. 相似文献
29.
BACKGROUND: Heme oxygenase-1 (HO-1) is a 32-kDa stress protein that catalyzes the degradation of heme to biliverdin. HO-1 immunoreactivity is greatly increased in neurons and astrocytes of the hippocampus and cerebral cortex of individuals with AD and colocalizes to senile plaques and neurofibrillary tangles. METHODS: We investigated whether systemic HO-1 regulation is also deranged in AD patients and whether blood HO-1 measurements provide a peripheral biomarker of the disease. Plasma HO-1 protein levels were measured by competitive ELISA and lymphocyte HO-1 mRNA levels were determined by Northern analysis in patients with early probable sporadic AD, normal elderly controls (NEC), normal younger controls, individuals with age-associated cognitive decline (AACD) not meeting AD criteria, and patients with non-Alzheimer dementia, nondementing neurologic illness, and chronic medical disorders. CSF HO-1 protein concentrations were also determined by ELISA in pathologically confirmed AD and control cases. RESULTS: Mean plasma HO-1 protein concentrations were significantly lower in AD patients (0.85 +/- 0.14 microg/mL) compared with NEC (1.77 +/- 0.34 microg/mL; p < 0.05) and control patients. The AACD group exhibited plasma HO-1 concentrations (1.06 +/- 0.33 microg/mL) intermediate between, but not different from, those of the AD patients and NEC. Lymphocyte HO-1 mRNA levels were lower in the AD cohort relative to NEC (p < 0.001) and individuals with AACD, non-Alzheimer dementia, nondementing neurologic illness, and chronic medical conditions. Lymphocyte HO-1 mRNA levels were also lower in the AACD group relative to NEC (p < 0.05). In comparison with all groups excluding AACD, the sensitivity and specificity of lymphocyte HO-1 mRNA measurement for diagnosis of early sporadic AD are 88% and 75%. Mean CSF HO-1 protein concentrations were lower (p < 0.01) in AD cases (19.07 ng/mL) relative to control values (32.48 ng/mL). CONCLUSIONS: Plasma and CSF HO-1 protein and lymphocyte HO-1 mRNA levels are decreased in subjects with sporadic AD. Quantitative assay for lymphocyte HO-1 mRNA expression may serve as a useful biologic marker in early sporadic AD. 相似文献
30.
BACKGROUND: Recent studies indicate that N-terminally bis-ethylated-polyamine analogs have significant antitumor activity in several human solid-tumor models. In this study, the in vitro and in vivo antitumor potential of the polyamine analog N(1), N(11)-diethylnorspermine (DENSpm) in human prostate carcinoma cells was examined. METHODS: The antiproliferative and biochemical effects of DENSpm were tested in four human prostate cancer cell lines, i.e., PC-3, TSU-pr1, DU-145, and JCA-1. The in vivo antitumor potential was explored in two groups of nude mice bearing small or more developed xenografts of the DU-145 cell line. The mice were treated with 40 mg/kg DENSpm, three times per day for two cycles of 6 days, on days 1-6 and 8-13. RESULTS: In vitro studies showed that all four tested human prostate carcinoma cell lines were sensitive to DENSpm in micromolar concentrations. In tumor-bearing mice, DENSpm clearly prevented tumor growth in both size groups, which became significant after day 17. Treatment with DENSpm evoked intracellular accumulation of the analog and various regulatory responses, e.g., downregulation of the polyamine biosynthesis, the induction of the catabolic enzyme spermidine/spermine N(1)-acetyltransferase (SSAT), and the depletion or decrease of natural polyamines. The cellular sensitivity to growth inhibition by DENSpm only correlated with the degree of ODC inhibition and SSAT induction. CONCLUSIONS: DENSpm has sustained inhibitory effects on the growth of human prostate carcinoma cells in vitro as well in vivo. This polyamine analog may provide a new tool in the chemotherapy of prostate cancers with various phenotypes. 相似文献