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排序方式: 共有1207条查询结果,搜索用时 578 毫秒
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Pia Lautala Maija Kivimaa Hannele Salomies Eivor Elovaara Jyrki Taskinen 《Pharmaceutical research》1997,14(10):1444-1448
Purpose. Nitrocatechol COMT inhibitors are a new class of bioactive compounds, for which glucuronidation is the most important metabolic pathway. The objective was to characterize the enzyme kinetics of nitrocatechol glucuronidation to improve the understanding and predicting of the pharmacokinetic behavior of this class of compounds.
Methods. The glucuronidation kinetics of seven nitrocatechols and 4-nitrophenol, the reference substrate for phenol UDP-glucuronosyltrans-ferase activity, was measured in liver microsomes from creosote-treated rats and determined by non-linear fitting of the experimental data to the Michaelis-Menten equation. A new method that combined densitometric and radioactivity measurement of the glucuronides separated by HPTLC was developed for the quantification.
Results. Apparent Km values for the nitrocatechols varied greatly depending on substitution pattern being comparable with 4-nitrophenol (0.11 mM) only in the case of 4-nitrocatechol (0.19 mM). Simple nitrocatechols showed two-fold Vmax values compared with 4-nitrophenol (68.6 nmol min–1 mg–1), while all disubstituted catechols exhibited much lower glucuronidation rate. Vmax/Km values were about 10 times higher for monosubstituted catechols compared to disubstituted ones. The kinetic parameters for COMT inhibitors were in the following order: Km nitecapone >> entacapone > tolcapone; Vmax nitecapone > entacapone > tolcapone; Vmax/Km tolcapone > nitecapone > entacapone.
Conclusions. Nitrocatechols can in principle be good substrates of UGTs. However, substituents may have a remarkable effect on the enzyme kinetic parameters. The different behaviour of nitecapone compared to the other COMT inhibitors may be due to its hydrophilic 5-substituent. The longer elimination half-life of tolcapone in vivo compared to entacapone could not be explained by glucuronidation kinetics in vitro. 相似文献
5.
E Harju 《International surgery》1990,75(1):27-35
The findings on dumping syndrome (DS) are not consistent considering its relations with age, sex, weight/height, smoking habits, race, dose of oral glucose, the time elapsed since surgery, the function of exocrine pancreas nor the duration of ulcer symptoms. The patients after total gastrectomy (TG) may present relative postprandial lack of insulin. As a sign of long-term hyperglycemia elevated HbA1 has been measured in DS patients. Oral galactose test may reveal new features of DS. Abnormalities in splanchnic blood circulation as well as release of intestinal hormones are involved with DS. Dietary habits including fibers, pectin and guar gum, play a central role in the prevention and treatment of DS. In unresponsive cases several operative methods have been applied with success. Alkaline reflux gastritis is most often seen after B II and I reconstructions and after pyloroplasty. Chronic diarrhea follows mostly after truncal vagotomy. Ten to 50% of patients after gastrectomy (GE) waste 10 to 20% of their body weight because of decreased food, energy, vitamin and mineral intake caused by eating-related symptoms. Vitamin and mineral supplements, a small snack 20 min before the major meal, digestive enzymes, treatment of colonization with antibiotics and protein foods may help. About 50% of GE patients show iron deficiency anemia. Easily dissolved iron between meals with ascorbic acid give the most effective response. Deficiency of vitamin B12 or of folate may develop as megaloblastic anemia. B12 supplement and antibiotics are effective in bacterial overgrowth, but surgical correction is necessary in troublesome blind loop. Folic acid deficiency is corrected by oral folic acid.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
6.
The nutritional state of 32 patients after (mean 66 months) colon interposition due to benign oesophageal disease was examined. Forty-four per cent of the patients had depleted iron stores (low serum ferritin concentration). Serum iron and blood haemoglobin concentrations were lower (P less than 0.001) in those with low than in those with normal serum ferritin concentration (115 +/- 12 g/l and 15 +/- 5 mumol/l vs 135 +/- 12 g/l and 23 +/- 9 mumol/l). Most very low blood haemoglobin concentrations (less than 110 g/l) were found in patients with depleted iron stores. Eighteen patients had serum albumin concentrations slightly below (35-39 g/l) the normal range, and two other patients had values less than 35 g/l. The patients had less dietary iron (13 +/- 6 mg/d) than age- and sex-matched controls (19 +/- 7 mg/d), but the intake of patients with depleted iron stores (12 +/- 5 mg/d) was similar to that of patients with normal iron stores (14 +/- 6 mg/d). Symptoms and/or the replacement of colon graft anti- or isoperistaltically did not have any significant association with the nutritional status, only slightly reduced blood haemoglobin and serum albumin concentration were found among the symptomatic patients and the patients with an antiperistaltic graft. Iron therapy and protein supplements, eg, from milk, egg, soy and meat, are recommended as the dietary treatment. To improve the nutritional status a short intra-abdominal colon graft loop anastomosed to the proximal stomach instead of long loop with an antral anastomosis of the present patients is suggested. 相似文献
7.
Bacteriophage PRD1 is an icosahedral dsDNA virus with a diameter of 740 A and an outer protein shell composed of 720 copies of major coat protein P3. Spike complexes at the vertices are composed of a pentameric base (protein P31) and a spike structure (proteins P5 and P2) where the N-terminal region of the trimeric P5 is associated with the base and the C-terminal region of P5 is associated with receptor-binding protein P2. The functionality of proteins P3 and P5 was investigated using insertions and deletions. It was observed that P3 did not tolerate changes whereas P5 tolerated changes much more freely. These properties support the hypothesis that viruses have core structures and functions, which remain stable over time, as well as other elements, responsible for host interactions, which are evolutionally more fluid. The insertional probe used was the apex of exposed loop 4 of group B meningococcal outer membrane protein PorA, a medically important subunit vaccine candidate. It was demonstrated that the epitope could be displayed on the virus surface as part of spike protein P5. 相似文献
8.
Wikman H Nymark P Väyrynen A Jarmalaite S Kallioniemi A Salmenkivi K Vainio-Siukola K Husgafvel-Pursiainen K Knuutila S Wolf M Anttila S 《Genes, chromosomes & cancer》2005,42(2):193-199
Several chromosomal regions are recurrently amplified or deleted in lung tumors, but little is known about the underlying genes, which could be important mediators in tumor formation or progression. In lung cancer, the RB1-CCND1-CDKN2A pathway, involved in the G1-S transition, is damaged in nearly all tumors. In the present study, we localized a novel amplicon in lung tumors to a fragment of less than 0.5 Mb at 12q13.3-q14.1 by using comparative genomic hybridization (CGH) on cDNA microarrays. This approach enabled us to identify 10-15 genes with the most consistent amplifications. Semiquantitative RT-PCR analyses of 13 genes in this region showed that four of them (CDK4, CYP27B1, METTL1, and TSFM) were also highly up-regulated. Immunohistochemical (IHC) analysis of 141 tumor samples on a tissue microarray showed that CDK4 was expressed at a high level in 23% of lung tumors. Six (21.4%) of the tumors with high CDK4 expression (n = 28) were shown by fluorescence in situ hybridization (FISH) to contain the 12q13.3-q14.1 amplification. For CDK4, a positive correlation was found between gene copy number (FISH and CGH array), mRNA expression (RT-PCR), and level of protein expression (IHC). CDK4 expression did not correlate with CDKN2A methylation status. Amplification of CDK4 has been described in other tumor types, but its role in lung cancer remains to be elucidated. Although CDK4 amplification seems to be a relatively rare event (4.3%) in lung tumors, it indicates the significance of the RB1-CCND1 pathway in lung tumorigenesis. 相似文献
9.
Comparative typing of Campylobacter jejuni by heat-stable serotyping and PCR-based restriction fragment length polymorphism analysis 总被引:2,自引:0,他引:2
Campylobacter jejuni has become the most common bacterial cause of human gastroenteritis worldwide. Rapid, discriminatory typing methods are required to identify potential clusters of infections. The major disadvantage of the well-evaluated and widely used Penner heat-stable serotyping method is the high level of nontypeability. The correlation of the types determined by the Penner heat-stable serotyping method and PCR-based restriction fragment length polymorphism (RFLP) analysis of the lipooligosaccharide (LOS) biosynthesis genes of C. jejuni was studied with 149 C. jejuni strains. Of these strains, 79 were patient strains belonging to 25 Penner serotypes, 60 were nontypeable patient strains, and 10 were reference strains. A 9.6-kb DNA fragment of the LOS gene cluster was amplified and digested with the restriction enzymes HhaI and DdeI. Altogether, 39 different RFLP types (including 30 HhaI profiles and 32 DdeI profiles) were identified. Type Hh1Dd1 was the most common type, with 36% of the strains and strains of 12 serotypes being of this type. A high level of discrimination was obtained, and a correlation between the Penner serotypes and the PCR-RFLP types could be seen. Also, variation in the LOS biosynthesis genes within a single Penner serotype was found. Although the PCR-RFLP method may not be sufficient to compensate for Penner serotyping, it can give valuable information about nontypeable strains and further characterize strains of common serotypes. 相似文献
10.
Kristina Virkola Maija Lappalainen Leena Valanne Marjaleena Koskiniemi 《Pediatric radiology》1997,27(2):133-138
A total of 44 181 serum samples from 16 733 pregnant women were analyzed for findings suggesting primary Toxoplasma infection. Thirty-seven newborns exposed to maternal primary Toxoplasma infection in utero were studied prospectively with ultrasound, CT, and MRI for signs of intrauterine infection. Their mothers
had been treated during pregnancy, and all infants were treated. The children were assigned to three groups according to their
mothers' serological status, and the radiological results were compared with the clinical outcome. Although radiological signs
were scarce, ultrasound findings combined with maternal serology were found to be significantly related to clinical outcome.
Received: 19 October 1994 Accepted: 28 April 1996 相似文献