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排序方式: 共有112条查询结果,搜索用时 31 毫秒
1.
Simultaneous assay of felbamate plus carbamazepine, phenytoin, and their metabolites by liquid chromatography with mobile phase optimization 总被引:1,自引:0,他引:1
Felbamate is an investigational antiepileptic drug (AED) in clinical trials. A high-performance liquid chromatographic method for the simultaneous analysis of felbamate, phenytoin (PHT), 5-(p-hydroxyphenyl)-5-phenylhydantoin, carbamazepine (CBZ), carbamazepine-10,11-epoxide, and carbamazepine-10,11-diol in serum was developed by a mobile phase optimization technique. Capacity factors for the compounds of interest and 12 other AEDs and metabolites were determined with mixtures of methanol, acetonitrile, or tetrahydrofuran and a 0.01 M ammonium phosphate buffer, pH 6.5, on a reversed-phase C8 column. An optimized mobile phase composition was determined that could separate the compounds of interest and three internal standards in less than 15 min. Serum was extracted with CH2Cl2/ethyl acetate (2:1) after addition of three internal standards. The method was validated for within-day and between-day precision and accuracy for the six compounds. Coefficients of variation were generally less than 10% at all concentrations and less than 5% in the typical therapeutic range for each compound. The lower limit of detection was estimated at 0.2 micrograms/ml for CBZ and its metabolites and 0.5 micrograms/ml for felbamate and PHT. For felbamate, the lowest point on the standard curve was 1.88 micrograms/ml with a between-day variability of 10.3%. The assay was used to determine the serum concentrations of PHT and CBZ and its metabolites in a subject before, during, and after felbamate therapy. 相似文献
2.
E. Remmel H. Zirngibl und Ch. Gebhardt 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》1987,372(1):878
Summary Hemorrhage through the pancreatic duct is a form of upper gastrointestinal bleeding that is rarely described in the literature. Since 1981, we have observed ten cases of hemosuccus pancreaticus due to pancreatitis and one as a complication of an islet-cell carcinoma. The diagnosis of hemosuccus was made ten times preoperatively: eight times by checking the ERP; six times blood was seen coming out of the papilla of Vater/papilla minor; in five cases there were typical findings in the pancreatogram. Angiography showed extravasation in five cases. In our opinion, partial pancreatectomy should be the treatment of choice for pancreatitis in combination with hemosuccus pancreaticus.Zusammenfassung Blutungen über den Ductus Wirsungianus gehören zu den selten beschriebenen Blutungsursachen im oberen Gastrointestinaltrakt. Seit 1981 konnten wir insgesamt 11 Fälle von Pankreasgangblutungen, 10 davon bei Pankreatitiden, beobachten. Achtmal konnte die Diagnose Haemosuccus pancreaticus mittels ERP gestellt werden: Blutaustritt bei der Duodenoskopie sechsmal, typische Kontrastmittelaussparungen im Röntgenbild fünfmal. In der Angiographie zeigten sich bei fünf Patienten Extravasate. (Keine präoperative Diagnose in einem Fall.) Die Teilresektion des Pankreas halten wir für die Therapiemethode der Wahl bei Pankreatitiden mit dieser Komplikation. 相似文献
3.
Responses of long descending propriospinal neurons to natural and electrical types of stimuli in cat
Long descending propriospinal (LDP) neurons (antidromically identified) having cell bodies of origin in the cervical enlargement and projecting axons at least as far as the L2 segment were studied. Extracellular recording of responses to natural and electrical stimuli was done in high-spinal cats.
- (1) A receptive field for natural stimuli was found for 123 LDP neurons. An additional 108 LDP cells were not activated by the natural stimuli used, but some of these fired spike potentials in response to electrical stimulation of peripheral nerves of the forelimb. There was no distinction between neurons activated and those not activated by natural stimuli on the basis of location or conduction velocity.
- (2) The most effective natural stimuli were mechanical manipulation of the skin (both low and high threshold), movement of joints of the paw, and pressure to the deep tissues, especially to the extensor side of the arm. These modalities of stimuli were most often excitatory, but could be inhibitory as well.
- (3) On the basis of modality, 4 subgroups of LDP cells were identified: those which were responsive only to mechanical-cutaneous, joint-movement, or deep-pressure stimuli, and those which responded to several of these modalities of stimuli, the multimodal group. These subgroups could not be distinguished on the basis of conduction velocity.
- (4) The receptive fields varied in size from small (one digit) to large (all of a forelimb). For single LDP cells they included ones with single and/or multimodal input from one or both forelimbs and various combinations of excitation and/or inhibition. However, those in the dorsal horn had only ipsilateral receptive fields, mainly of the mechanical-cutaneous type. Cells with bilateral receptive fields were mainly located medially in the ventral gray in laminae VII and VIII.
- (5) A comparison of the location of the subtypes of LDP cells revealed that neurons activated by mechanical-cutaneous stimuli were in laminae I and IV–VIII; whereas deep-pressure and multimodal activated neurons were almost exclusively in laminae VII and VIII.
- (6) LDP cells receiving input from deep-pressure receptors in the extensor muscles of the arm, joint-movement, or deep-pressure receptors of the paw probably relay position or weight-bearing information about the forelimbs to the lumbosacral spinal cord. This arrangement suggests that LDP neurons function in interlimb coordination and would be active during locomotion. They probably participate also in other reflexes elicited by cutaneous and deep stimuli.
Keywords: propriospinal neurons; spinal cord; natural stimulation 相似文献
4.
PURPOSE: Interruption of oral drug administration poses a significant clinical problem for antiepileptic drugs that have no parenteral formulation. If a drug is absorbed rectally, rectal administration can be a useful alternative when the oral route of administration is not possible. The purpose of this study was to compare the single-dose pharmacokinetics of lamotrigine (LTG) compressed tablets after rectal and oral administration in healthy volunteers. METHODS: A single LTG compressed tablet (100 mg) was administered orally and rectally to 12 volunteers in this single-dose, two-period, crossover study with a 2-week washout between doses. For rectal administration, tablets were crushed and suspended in 10 mL of water. Plasma samples were collected from 0 to 120 hr after each dose and analyzed for LTG by an HPLC method developed for this investigation. RESULTS: LTG plasma concentrations were lower after rectal administration versus oral administration. The average area under the curve was 28.90 +/- 9.5 microg/mL/hr after rectal administration and 51.71 +/- 19.2 microg/mL/hr after oral administration. The average maximum LTG concentration was 0.53 +/- 0.14 microg/mL after rectal administration and 1.45 +/- 0.35 microg/mL after oral administration. The relative bioavailability for LTG compressed tablets was 0.63 +/- 0.33 for rectal administration. There were no drug-related rashes or serious side effects. CONCLUSIONS: LTG suspension prepared from LTG compressed tablets is absorbed rectally, although not to the same extent or rate as when given orally. 相似文献
5.
Biochemically based design of cyclooxygenase-2 (COX-2) inhibitors: facile conversion of nonsteroidal antiinflammatory drugs to potent and highly selective COX-2 inhibitors 下载免费PDF全文
Kalgutkar AS Crews BC Rowlinson SW Marnett AB Kozak KR Remmel RP Marnett LJ 《Proceedings of the National Academy of Sciences of the United States of America》2000,97(2):925-930
All nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the cyclooxygenase (COX) isozymes to different extents, which accounts for their anti-inflammatory and analgesic activities and their gastrointestinal side effects. We have exploited biochemical differences between the two COX enzymes to identify a strategy for converting carboxylate-containing NSAIDs into selective COX-2 inhibitors. Derivatization of the carboxylate moiety in moderately selective COX-1 inhibitors, such as 5,8,11,14-eicosatetraynoic acid (ETYA) and arylacetic and fenamic acid NSAIDs, exemplified by indomethacin and meclofenamic acid, respectively, generated potent and selective COX-2 inhibitors. In the indomethacin series, esters and primary and secondary amides are superior to tertiary amides as selective inhibitors. Only the amide derivatives of ETYA and meclofenamic acid inhibit COX-2; the esters are either inactive or nonselective. Inhibition kinetics reveal that indomethacin amides behave as slow, tight-binding inhibitors of COX-2 and that selectivity is a function of the time-dependent step. Site-directed mutagenesis of murine COX-2 indicates that the molecular basis for selectivity differs from the parent NSAIDs and from diarylheterocycles. Selectivity arises from novel interactions at the opening and at the apex of the substrate-binding site. Lead compounds in the present study are potent inhibitors of COX-2 activity in cultured inflammatory cells. Furthermore, indomethacin amides are orally active, nonulcerogenic, anti-inflammatory agents in an in vivo model of acute inflammation. Expansion of this approach can be envisioned for the modification of all carboxylic acid-containing NSAIDs into selective COX-2 inhibitors. 相似文献
6.
7.
Prognostic relevance of MAGE-A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: a tissue microarray study 总被引:4,自引:0,他引:4
Kocher T Zheng M Bolli M Simon R Forster T Schultz-Thater E Remmel E Noppen C Schmid U Ackermann D Mihatsch MJ Gasser T Heberer M Sauter G Spagnoli GC 《International journal of cancer. Journal international du cancer》2002,100(6):702-705
TAAs of the MAGE family are mostly studied as targets of specific immune responses. Their potential relevance as tumor markers has also been underlined. We used a MAb, 57B, recognizing MAGE-A4 protein in paraffin-embedded sections, to evaluate its expression in bladder cancers by employing TMA including 2,317 samples from 1,849 patients. In 2,090/2,317 cases (90.2%), immunostaining yielded interpretable results. Since for some patients more than 1 sample was available, only interpretable first biopsies (n = 1,628) were considered. MAGE-A4 protein was expressed at significantly (p < 0.001) higher frequency in squamous (25/55, 45.5%) than in adeno (4/15, 26.7%), sarcomatoid (4/14, 28.6%), small cell (5/20, 25%) or transitional cell (281/1,522, 18.5%) carcinomas. In TCCs, overall MAGE-A4 positivity was significantly correlated with invasive phenotype (p < 0.001) and high tumor grade (p < 0.0001). Clinical data from 908 TCC patients were retrospectively evaluated, revealing that strong 57B staining was highly significantly associated with decreased tumor-specific survival (p < 0.0001). These data suggest that evaluation of MAGE-A4 protein expression is useful in the identification of groups of TCCs characterized by severe prognosis, thus possibly providing indications for early MAGE TAA-targeted immunotherapy. 相似文献
8.
9.
Inhibition of phenytoin hydroxylation in human liver microsomes by several selective serotonin re-uptake inhibitors 总被引:4,自引:0,他引:4
Several case reports have indicated that the selective serotonin re-uptake inhibitor (SSRI) fluoxetine increases phenytoin blood levels when given concurrently. The mechanism of this drug-drug interaction has been attributed to inhibition of CYP2C9-catalyzed hydroxylation of phenytoin to its major oxidative metabolite in humans, para-hydroxyphenyl phenyl hydantoin (HPPH). With a bank of human liver microsomes (HLM), four SSRIs (fluoxetine, norfluoxetine, sertraline, and paroxetine) were tested for inhibition of HPPH formation. Initially, the K(m) and V(max) values of phenytoin hydroxylation to HPPH were determined in the individual HLM samples. The average K(m) (n=8) was 9.7+/-2.9 microM. The V(max) varied fivefold, with an average value of 113+/-53 pmol HPPH/min/nmol CYP450. All of the SSRIs inhibited HPPH formation; resulting Ki values were 31.1+/-10.1 microM (fluoxetine) (n=5), 51.1+/-9.4 microM (norfluoxetine) (n=3), 52.2+/-21.5 microM (sertraline) (n=3), and 80.0+/-7.2 microM (paroxetine) (n=3). Sulfaphenazole (10 microM), utilized as a positive control for inhibition of HPPH formation, inhibited phenytoin hydroxylation (>95%) in all HLM samples. Diclofenac hydroxylation to 4'-OH diclofenac, a specific marker for CYP2C9 activity, was determined in HLM1-HLM6 and was highly correlated with HPPH formation in HLM1-HLM6, indicating that phenytoin hydroxylation in human liver microsomes is largely due to CYP2C9. This work presents direct evidence that the effect of fluoxetine on phenytoin blood levels may be explained by inhibition of CYP2C9-catalyzed phenytoin hydroxylation. In light of typical SSRI blood levels observed in patients, this study also suggests that the risk of a SSRI-phenytoin interaction is highest with fluoxetine and norfluoxetine, and less likely with sertraline and paroxetine. 相似文献
10.
Noppen C Lévy F Burri L Zajac P Remmel E Schaefer C Lüscher U Heberer M Spagnoli GC 《International journal of cancer. Journal international du cancer》2000,87(2):241-246
In this study, a computer-assisted reverse immunology approach was utilized in order to identify potentially antigenic peptides derived from the differentiation antigen TRP-2, a melanosomal protein frequently expressed in melanoma. Among the seven peptides complying with HLA-A2.1-binding motifs, two induced specific CD8(+) cytotoxic T lymphocytes. HLA-A2.1(+) melanoma cells expressing TRP-2 were lysed by clones specific for TRP-2(360-368) (TLDSQVMSL) peptide, thus identifying it as a naturally processed epitope. Other T-cell clones directed against TRP-2(476-484) (VMGTLVALV) were unable to lyse HLA-matched TRP-2(+) cell lines. The role of intracellular proteolytic processing in the generation of this epitope was investigated by transfecting mini-genes encoding the TRP-2(476-484) peptide alone or carrying N- or C-terminal extensions. Specific T-cell clones recognized target cells expressing the cytotoxic T-lymphocyte (CTL)-defined epitope or its C-terminally extended precursor, but failed to recognize cells expressing the N-terminally extended TRP-2(476-484) peptide, suggesting the presence of a negative processing signal (NPS). Regarding C-terminus-flanking regions, mutational analysis indicates that the GLY485 residue plays a key role in the processing of the TRP-2(476-484) epitope. Interestingly, proteasome inhibitors preventing the generation of the MART-1/Melan-A(27-35) immunodominant melanoma tumor-associated antigen (TAA) promoted detectable presentation of TRP-2(476-484) epitope in HLA-A2.1(+) and TRP-2(+) tumor lines, as witnessed by cytokine release by specific T-cell clones. 相似文献