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排序方式: 共有1210条查询结果,搜索用时 15 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
4.
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
5.
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
6.
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
7.
The purpose of this study was to determine changes in nasal respiratory pattern with growth and development, particularly to determine the age where upper airway growth ceases. The results on 361 healthy subjects, aged 7 to 24 years, based on aerodynamic measurements during rest breathing, showed clear differences between inspiratory and expiratory phases. Nasal airflow rate and cross-sectional area increased and oral-nasal pressure and nasal resistance decreased with age up to the age of 16, levelling by the age of 20 years. The body size and gender had effect only on nasal airflow rate. This study suggests that the measurements of the nasal respiratory pattern, determining impaired nasal airway, should be done during inspiration and using age-related assesment from a healthy population until the age of 16 years. From then on, guidelines for adults are applicable. 相似文献
8.
Tarja Anttila Leena Tenkanen Sonja Lumme Maija Leinonen Randi Elin Gislefoss G?ran Hallmans Steinar Thoresen Timo Hakulinen Tapio Luostarinen P?r Stattin Pekka Saikku Joakim Dillner Matti Lehtinen Matti Hakama 《Cancer epidemiology, biomarkers & prevention》2005,14(2):385-389
OBJECTIVE: We assessed the risk of prostate cancer by exposure to Chlamydia trachomatis. METHOD: Seven hundred thirty eight cases of prostate cancer and 2,271 matched controls were identified from three serum sample banks in Finland, Norway, and Sweden by linkage to the population based cancer registries. RESULTS: A statistically significant inverse association (odds ratio, 0.69; 95% confidence interval, 0.51-0.94) was found. It was consistent by different serotypes and there was a consistent dose-response relationship. CONCLUSION: C. trachomatis infection is not likely to increase the risk of prostate cancer. Whether the inverse relationship is true or due to difficulties in measuring the true exposure in prostatic tissue by serology, confounders or other sources of error remain open. 相似文献
9.
Johanna Raiman Maija Koljonen Katri Huikko Risto Kostiainen Jouni Hirvonen 《European journal of pharmaceutical sciences》2004,21(2-3):371-377
Poor absorption and stability of peptides are the major obstacles concerning the development of therapeutically relevant iontophoretic devices for the transdermal delivery of peptides. The present study examined the impact of constant and pulsed (direct/alternating) current profiles on the transport and stability of two decapeptides LHRH and Nafarelin. The stability of these peptides was studied in a physiological buffer solution, with electrical current, and when the peptide solution was exposed to the stratum corneum or to the epidermal/dermal side of human skin. Pulsed direct current profile was shown to be the most efficient in transporting both LHRH and Nafarelin across the human epidermis. Furthermore, the percentage of intact LHRH in the receiver phase was slightly higher when a pulsed current profile was used. Both the peptides were stable in a physiological buffer and under the influence of current, but LHRH was degraded especially in contact with the dermal side of the skin. Altogether five hydrolytic degradation products of LHRH were observed, and they were identified by LC-ESI/MS and LC-ESI/MS/MS. No degradation products of Nafarelin were observed. It is concluded that the pulsed direct current profile may provide at least a partial solution for the transdermal delivery of peptides in terms of improved transport efficacy and peptide stability. 相似文献
10.
Outi Honkanen Janne Marvola Hanna Kanerva Kai Lindevall Maija Lipponen Tommi Kekki Aapo Ahonen Martti Marvola 《European journal of pharmaceutical sciences》2004,21(5):428-678
The fate (movement and disintegration) of hard novel hydroxypropyl methylcellulose (HPMC) two-piece capsules in the human gastrointestinal tract was investigated using a gamma scintigraphic imaging method. Two different prolonged-release formulations without an active ingredient were used. The capsules contained different viscosity grades of HPMC powder (HPMC K100 and HPMC K4M). The aim was to determine the main reason why the pharmacokinetic profiles of model drugs change when the diluent was changed to a higher viscosity grade. The results were compared with our previous pharmacokinetic studies with corresponding capsules containing metoclopramide hydrochloride or ibuprofen as a model drug. The first observation was that the HPMC capsules had a tendency to attach to the oesophagus. Therefore, it is recommended that the HPMC capsules as well as gelatine capsules be taken with a sufficient amount of water (150–200 ml) in an upright position and maintaining the upright position for several minutes. The viscosity grade of the HPMC did not affect the transit times of the capsules in the GI tract. The major differences between the two formulations were the complete disintegration times of the capsules and the spreading of the capsules to the large intestine. Most of the HPMC K100-based capsules were completely disintegrated during the 8 h study, whereas the HPMC K4M-based capsules still exhibited plug formations in the large intestine. Also the HPMC K100-based capsules spread better to the ascending colon than the HPMC K4M-based capsules. The faster disintegration of the HPMC K100-based capsules explains the differences in the pharmacokinetic profiles of the model drugs between the HPMC K100- and K4M-based capsules in our previous studies. The main absorption site of the drugs from the capsules studied here is probably the large intestine when taken in a fasting state. 相似文献