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排序方式: 共有874条查询结果,搜索用时 31 毫秒
1.
Stijnen Annemiek M. Hovinga Suzanne Langemeijer Mariska W. E. Hoogerkamp Arendien van Bezooijen Cornells F. A. Danhof Meindert 《Pharmaceutical research》1993,10(7):1046-1051
The aim of the present investigations was to study the influence of increasing age on the pharmacodynamics of valproate in BN/BiRij rats, applying a threshold for electrically induced localized seizure activity as a measure of the anticonvulsant effect. Seven groups of healthy male BN/BiRij rats were used, aged 3, 6, 12, 19, 25, 31, and 37 months. Individual plasma concentration versus anticonvulsant effect relationships were determined during a continuous intravenous infusion of sodium valproate at a rate of 5.5 mg/min/kg. The infusion was terminated when the anticonvulsant effect intensity had reached the maximum attainable level or at a total infusion time of three hours. A nonlinear relationship between valproate concentration and anticonvulsant effect intensity was observed with no maximal effect in the concentration range up to 1200 mg · L–1. With increasing age a parallel shift in the concentration versus anticonvulsant effect relationships toward lower concentrations occurred. Thus increasing age appears to be associated with an increased sensitivity to the anticonvulsant effect of valproate.Suzanne Hovinga: Deceased January 30, 1991. 相似文献
2.
The effect of dantrolene sodium in relation to blood levels in spastic patients after prolonged administration. 总被引:1,自引:0,他引:1 下载免费PDF全文
W J Meyler H Bakker J J Kok S Agoston H Wesseling 《Journal of neurology, neurosurgery, and psychiatry》1981,44(4):334-339
In 25 patients with spasticity, pharmacokinetics and effects of dantrolene sodium were investigated after prolonged administration. A beneficial effect occurred in seven patients. The results were better on 100 mg daily than on a higher daily dose. An increase of the daily dose from 200 to 400 mg was not associated with higher blood levels. Many side effects were noted such as: anorexia, nausea, drowsiness, depression and muscle weakness. From this study we conclude that dantrolene sodium is a muscle relaxant with a weak to moderate effect in patients with spasticity; the effect at doses higher than 200 mg daily is probably poor. 相似文献
3.
4.
Keratitis caused by Scedosporium apiospermum successfully treated with a cornea transplant and voriconazole 总被引:2,自引:0,他引:2 下载免费PDF全文
Nulens E Eggink C Rijs AJ Wesseling P Verweij PE 《Journal of clinical microbiology》2003,41(5):2261-2264
A case of Scedosporium apiospermum keratitis was successfully treated with oral voriconazole and penetrating keratoplasty. Voriconazole levels in the aqueous humor were 53% of the levels in plasma and exceeded the MIC for the isolate by sevenfold. 相似文献
5.
High expression of MDR1, MRP1, and MRP3 in the hepatic progenitor cell compartment and hepatocytes in severe human liver disease 总被引:8,自引:0,他引:8
An increase in bile ductular structures is observed in diverse human liver diseases. These structures harbour the progenitor cell compartment of the liver. Since ATP-binding cassette (ABC) transporters may have a cytoprotective role in liver disease, an immunohistochemical study was performed on human liver specimens from patients with primary biliary cirrhosis (PBC), chronic hepatitis C virus (HCV) infection, submassive cell necrosis, and normal liver. The expression of MDR1, MDR3, BSEP, MRP1, MRP2, and MRP3 was determined using specific antibodies. Dilution series were constructed to determine the critical staining level in order to estimate the factor of up-regulation. In normal liver, hepatocytes showed canalicular staining for MDR3, BSEP, and MRP2. MDR1 stained the canalicular membrane of hepatocytes as well as that of cholangiocytes. MRP3 showed low immunoreactivity of bile duct epithelial cells and centrilobular hepatocytes only. Normal liver showed no immunoreactivity for MRP1. In diseased liver, the expression of MDR3, BSEP, and MRP2 was relatively stable. In PBC, HCV, and submassive necrosis, the expression levels of MDR1, MRP1, and MRP3 were increased. The strongest immunoreactivity was seen after submassive necrosis, where remaining islands of hepatocytes showed strong canalicular staining for MDR1 and MRP3. Regenerating bile ductules at the interface of portal tracts and necrotic areas stained intensely for MDR1, MRP1, and MRP3. In conclusion, MDR1, MRP1, and MRP3 are up-regulated in hepatocytes in severe human liver disease. Strong MDR1, MRP1, and MRP3 reactivity is seen in regenerating human bile ductules. 相似文献
6.
Agrin is a major heparan sulfate proteoglycan accumulating in Alzheimer's disease brain 总被引:4,自引:0,他引:4 下载免费PDF全文
Verbeek MM Otte-Höller I van den Born J van den Heuvel LP David G Wesseling P de Waal RM 《The American journal of pathology》1999,155(6):2115-2125
Heparan sulfate proteoglycans (HSPGs) have been suggested to play an important role in the formation and persistence of senile plaques and neurofibrillary tangles in dementia of the Alzheimer's type (DAT). We performed a comparative immunohistochemical analysis of the expression of the HSPGs agrin, perlecan, glypican-1, and syndecans 1-3 in the lesions of DAT brain neocortex and hippocampus. Using a panel of specific antibodies directed against the protein backbone of the various HSPG species and against the glycosaminoglycan (GAG) side-chains, we demonstrated the following. The basement membrane-associated HSPG, agrin, is widely expressed in senile plaques, neurofibrillary tangles and cerebral blood vessels, whereas the expression of the other basement membrane-associated HSPG, perlecan, is lacking in senile plaques and neurofibrillary tangles and is restricted to the cerebral vasculature. Glypican and three different syndecans, all cell membrane-associated HSPG species, are also expressed in senile plaques and neurofibrillary tangles, albeit at a lower frequency than agrin. Heparan sulfate GAG side chains are also associated with both senile plaques and neurofibrillary tangles. Our results suggest that glycosaminoglycan side chains of the HSPGs agrin, syndecan, and glypican, but not perlecan, may play an important role in the formation of both senile plaques and neurofibrillary tangles. In addition, we speculate that agrin, because it contains nine protease-inhibiting domains, may protect the protein aggregates in senile plaques and neurofibrillary tangles against extracellular proteolytic degradation, leading to the persistence of these deposits. 相似文献
7.
E. van der Veur B. S. ten Berge A. J. M. Donker J. F. May F. H. Schuurman H. Wesseling 《European journal of clinical pharmacology》1985,28(5):507-511
Summary After screening two local populations in the northern part of The Netherlands for hypertension, patients with a diastolic pressure (DP) between 95 and 120 mmHg were treated daily either with 50 mg hydrochlorothiazide or 100 mg atenolol. Non-responders were given the combination and if necessary the dose of atenolol was increased to 200 mg. Non-responders to the latter combination were randomized and treated either with 50 mg hydrochlorothiazide and labetalol or with 50 mg hydrochlorothiazide, 200 mg atenolol and prazosin. If after 1 month a DP90 mmHg had been reached the patient was reassessed after a further 3 months. If a DP>90 mmHg was found the dose of labetalol or prazosin was increased and the patient was re-examined after 1 month.This protocol was followed until the maximum dose was reached or adverse reactions prevented a further increase in dosage.During 6 months of treatment there was a further drop in systolic and diastolic blood pressures under both regimens of, respectively, 8.6 and 2.4 mmHg for labetalol, and 7.7 and 5.0 mmHg for the prazosin group. At the end of the period the average daily doses of labetalol and prazosin were 1256 mg and 4.3 mg, respectively. There was no significant difference in the average number of complaints between the labetalol and the prazosin group. 相似文献
8.
Maria ATC van der Loos Ilse Hellinga Mariska C Vlot Daniel T Klink Martin den Heijer Chantal M Wiepjes 《Journal of bone and mineral research》2021,36(5):931-941
Bone geometry can be described in terms of periosteal and endocortical growth and is partly determined by sex steroids. Periosteal and endocortical apposition are thought to be regulated by testosterone and estrogen, respectively. Gender-affirming hormone (GAH) treatment with sex steroids in transgender people might affect bone geometry. However, in adult transgender people, no change in bone geometry during GAH was observed. In this study, we investigated changes in bone geometry among transgender adolescents using a gonadotropin-releasing hormone agonist (GnRHa) and GAH before achieving peak bone mass. Transgender adolescents treated with GnRHa and subsequent GAH before the age of 18 years were eligible for inclusion. Participants were grouped based on their Tanner stage at the start of GnRHa treatment and divided into early, mid, and late puberty groups. Hip structure analysis software calculating subperiosteal width (SPW) and endocortical diameter (ED) was applied to dual-energy X-ray absorptiometry scans performed at the start of GnRHa and GAH treatments, and after ≥2 years of GAH treatment. Mixed-model analyses were performed to study differences over time. Data were visually compared with reference values of the general population. A total of 322 participants were included, of whom 106 were trans women and 216 trans men. In both trans women and trans men, participants resembled the reference curve for SPW and ED of the experienced gender but only when GnRHa was started during early puberty. Those who started during mid and late puberty remained within the reference curve of the gender assigned at birth. A possible explanation might be sought in the phenomenon of programming, which conceptualizes that stimuli during critical windows of development can have major consequences throughout one's life span. Therefore, this study adds insights into sex-specific bone geometry development during puberty of transgender adolescents treated with GnRHa, as well as the general population. © 2021 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research. 相似文献
9.
Lue?en Henrik. L. de Leeuw Bas. J. Langeme?er Mariska W. E. de Boer A. G. Verhoef J. Coos. Junginger Hans E. 《Pharmaceutical research》1996,13(11):1668-1672
Purpose. To evaluate the effect of the crosslinked poly(acrylate) carbomer 934P (C934P) and its freeze-dried neutralized sodium salt (FNaC934P) as well as chitosan hydrochloride on the intestinal absorption of the peptide drug buserelin.
Methods. Buserelin was applied intraduodenally in control buffer, 0.5% (w/v) C934P, 0.5% (w/v) FNaC934P, 1.5% (w/v) chitosan hydrochloride or FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture in rats.
Results. All polymer preparation showed a statistically significant improvement of buserelin absorption compared to the control solution. The absolute bioavailabilities for the different polymer preparations were: control, 0.1%; 0.5% FNaC934P, 0.6%; 0.5% C934P, 2.0%; chitosan hydrochloride, 5.1% and FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture, 1.0%. The higher bioavailability with chitosan hydrochloride compared to C934P and FNaC934P indicates that for buserelin the intestinal transmucosal transport enhancing effect of the polymer plays a more dominant role than the protection against proteases such as -chymotrypsin.
Conclusions. The mucoadhesive polymers carbomer 934P and chitosan hydrochloride are able to enhance the intestinal absorption of buserelin in vivo in rats, and may therefore be promising excipients in peroral delivery systems for peptide drugs. 相似文献
10.
B van der Vegt M H E Doting P L Jager J Wesseling J de Vries 《European journal of surgical oncology》2004,30(7):715-720
Sentinel lymph node biopsy (SLNB) without further axillary dissection in patients with sentinel node-negative breast carcinoma appears to be a safe procedure to ensure locoregional control. During a median follow-up of 35 months the false-negative rate was 1% in our study population of 185 patients. BACKGROUND: The objective of this prospective study is to provide data on follow-up of patients with primary operable breast carcinoma staged with SLNB without axillary lymph node dissection (ALND) if the sentinel lymph nodes (SLNs) were tumour-negative. METHODS: One hundred and eighty-five patients were enrolled. Preoperative dynamic and static lymphoscintigraphy were performed; both a vital blue dye and a gamma detection probe were used intraoperatively. Patients with tumour-positive SLNs received completion ALND or if no SLNs could be identified. All patients were monitored according to regional follow-up protocols. RESULTS: The SLNs were identified in 179 out of the 185 patients. In 73 patients the SLNs were tumour-positive and in 106 patients tumour-negative. The median follow-up was 35 months (range 17-59). In one SLN-negative patient an axillary recurrence occurred 26 months after the SLNB (false-negative rate: 1%). CONCLUSIONS: SLNB without ALND appears to be a safe procedure to ensure locoregional control in SLN-negative breast carcinoma, if carried out by an experienced team. 相似文献