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排序方式: 共有372条查询结果,搜索用时 15 毫秒
1.
D McKillop K J Pickup A J Swaisland B F Holmes 《Xenobiotica; the fate of foreign compounds in biological systems》1990,20(4):401-415
1. Oral absorption and bioavailability of the orally active cardiotonic agent, (6RS)-6-methyl-5-(pyrid-4-yl)-3H,6H-1,3,4-[6-14C]thiadiaz in-2-one (MPTD) (5 mg/kg), in rat and baboon were high. Peak blood concentrations of MPTD and total radioactivity were reached by 1.5-4 h when MPTD accounted for 60-70% of total radioactivity. In both species, elimination of MPTD from blood was rapid (t 1/2 = 3-4 h), although total nonspecific radioactivity was eliminated more slowly. 2. Radioactivity was rapidly eliminated by both species mainly into urine. In rat, about 3% dose was collected as 14CO2 and 2% remained in the carcass after 4 days. Recovery from baboon was incomplete (78-86%). 3. Examination of urine indicated extensive metabolism of MPTD showing a marked species difference. In baboon, MPTD was metabolized largely by glucuronidation at the pyridyl nitrogen to yield a quaternary ammonium conjugate and only about 1% of the dose was excreted unchanged. In rat, the major urinary component was unchanged MPTD and no glucuronide conjugate was found. Both species formed the pyridine N-oxide of MPTD as well as a number of unidentified minor components. 4. Distribution of radioactivity in rat was rapid and extensive. In general, elimination from tissues was also rapid, although radioactivity was eliminated much more slowly from the nasal and bronchiolar epithelium and from the preputial gland. 相似文献
2.
R. Wilson J. H. McKillop M. MacLean J. J. Walker W. D. Fraser† C. Gray† F. Dryburgh† J. A. Thomson 《Clinical endocrinology》1992,37(4):331-334
OBJECTIVES: There is considerable controversy in the literature as to the cause of hyperemesis gravidarum. The aim of this project was to measure a range of thyroid hormone levels in a group of hyperemetic pregnant women. PATIENTS: The study was carried out in 10 first trimester pregnant women with hyperemesis gravidarum. All had been admitted to hospital due to the severity of their symptoms. Fifty age matched, healthy first trimester pregnant women were used as controls. MEASUREMENTS: Blood samples from the women were analysed for total T3 (TT3), total T4 (TT4), free T4 (FT4), TSH, thyrotrophin receptor antibodies (TRAb), thyroid stimulating antibodies (TSAb) and thyroid microsomal and thyroglobulin antibodies. Human chorionic gonadotrophin (hCG) levels were also measured. RESULTS: While individual patients were found to have some abnormal thyroid function tests the group as a whole showed no consistent pattern of abnormality and did not differ significantly from a group of healthy first trimester pregnant women. hCG levels were also within the normal range in the hyperemetic patients. DISCUSSION: None of the women in this study received any antithyroid medication and their symptoms improved as the pregnancy progressed. These results would suggest that there is no underlying thyroid abnormality in patients with hyperemesis gravidarum. It would appear that neither thyroid hormones, nor hCG contribute to the pathogenesis of the condition. 相似文献
3.
4.
Marie L. Smith William Martin James H. McKillop Ignac Fogelman 《European journal of nuclear medicine and molecular imaging》1984,9(11):519-520
In two patients with metastatic disease more lesions were detected on scintigraphs obtained with the low uptake bone-scanning agent dimethyl-amino-diphosphonate than on images produced using methylene diphosphonate. The results in these two patients provide practical support for the suggestion that bone-scanning agents with low uptake in normal bone, but high tumour-to-normal bone ratios, will allow better delineation of local bone abnormalities. 相似文献
5.
6.
James H. McKillop John Wallwork Bruce A. Reitz Margaret E. Billingham Richard Miller I. Ross McDougall 《European journal of nuclear medicine and molecular imaging》1982,7(4):162-165
Lymphocytes separated from venous blood from six dogs who had heterotopic cardiac transplants have been labeled using 111In-oxine. Labeled lymphocytes were reinjected into the dogs and imaging of the heart carried out over the successive 3 or 4 days. For comparison serial ECGs and punch biopsies of the heart were obtained. Abnormal uptake of labeled lymphocytes in the donor heart was clearly visible in three of the six dogs, faintly visible in two and not seen in one. 630 Ci 111In was used in the dog where no uptake was seen and subsequent studies showed this amount of the radiopharmaceutical was toxic to lymphocytes. In the remaining five dogs the mean ratio of uptake of 111In in donor to recipient heart was 14:1 (range 6.5:1–21:1). The lack of substantial uptake in the transplanted heart of two dogs is attributed to a delay in rejection relative to the time the labeled lymphocytes were injected. The results suggest that 111In-labeled lymphocytes have potential as a noninvasive test for detecting rejection of cardiac transplants.J. McKillop is a Harkness Fellow of the Commonwealth FundJ. Wallwork is supported by National Heart Research Fund (UK) 相似文献
7.
Alcohol and liver cancer. 总被引:5,自引:0,他引:5
Hepatocellular carcinoma is the eighth most frequent cancer in the world, accounting for approximately 500,000 deaths per year. Unlike many malignancies, hepatocellular carcinoma occurs predominantly within the context of known risk factors, with hepatic cirrhosis being the most common precursor to the development of hepatocellular carcinoma. After ethanol ingestion, the liver represents the major site of metabolism. Ethanol metabolism by alcohol dehydrogenase leads to the generation of acetaldehyde and free radicals that bind rapidly to numerous cellular targets, including components of cell signaling pathways and DNA. In addition to direct DNA damage, acetaldehyde depletes glutathione, an antioxidant involved in detoxification. Chronic ethanol abuse leads to induction of hepatocyte microsomal cytochrome P450 2E1, an enzyme that metabolizes ethanol to acetaldehyde and, in doing so, causes further free radical production and aberrant cell function. Cytochrome P450 2E1-dependent ethanol metabolism is also associated with activation of procarcinogens, changes in cell cycle, nutritional deficiencies, and altered immune system responses. The identification of oxidative stress in mediating many deleterious effects of ethanol in the liver has led to renewed interest in the use of dietary antioxidants as therapeutic agents. Included in this group are S-adenosyl-L-methionine and plant-derived flavanoids. 相似文献
8.
Demonstration of increased concentrations of circulating glycated insulin in human Type 2 diabetes using a novel and specific radioimmunoassay 总被引:2,自引:1,他引:2
AIMS/HYPOTHESIS: Glycation of insulin, resulting in impaired bioactivity, has been shown within pancreatic beta cells. We have used a novel and specific radioimmunoassay to detect glycated insulin in plasma of Type 2 diabetic subjects. METHODS: Blood samples were collected from 102 Type 2 diabetic patients in three main categories: those with good glycaemic control with a HbA(1c) less than 7%, moderate glycaemic control (HbA(1c) 7-9%) and poor glycaemic control (HBA(1c) greater than 9%). We used 75 age- and sex-matched non-diabetic subjects as controls. Samples were analysed for HbA(1c), glucose and plasma concentrations of glycated insulin and insulin. RESULTS: Glycated insulin was readily detected in control and Type 2 diabetic subjects. The mean circulating concentration of glycated insulin in control subjects was 12.6+/-0.9 pmol/l ( n=75). Glycated insulin in the good, moderate and poorly controlled diabetic groups was increased 2.4-fold ( p<0.001, n=44), 2.2-fold ( p<0.001, n=41) and 1.1-fold ( n=17) corresponding to 29.8+/-5.4, 27.3+/-5.7 and 13.5+/-2.9 pmol/l, respectively. CONCLUSION/INTERPRETATION: Glycated insulin circulates at noticeably increased concentrations in Type 2 diabetic subjects. 相似文献
9.
Kerri A Simo David J Niemeyer Erin M Hanna Jacob H Swet Kyle J Thompson David Sindram David A Iannitti Ashley L Eheim Eugene Sokolov Valentina Zuckerman Iain H McKillop 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2014,16(6):534-542
Background
Hepatic regeneration requires coordinated signal transduction for efficient restoration of functional liver mass. This study sought to determine changes in lysophosphatidic acid (LPA) and LPA receptor (LPAR) 1–6 expression in regenerating liver following two-thirds partial hepatectomy (PHx).Methods
Liver tissue and blood were collected from male C57BL/6 mice following PHx. Circulating LPA was measured by enzyme-linked immunosorbent assay (ELISA) and hepatic LPAR mRNA and protein expression were determined.Results
Circulating LPA increased 72 h after PHx and remained significantly elevated for up to 7 days post-PHx. Analysis of LPAR expression after PHx demonstrated significant increases in LPAR1, LPAR3 and LPAR6 mRNA and protein in a time-dependent manner for up to 7 days post-PHx. Conversely, LPAR2, LPAR4 and LPAR5 mRNA were barely detected in normal liver and did not significantly change after PHx. Changes in LPAR1 expression were confined to non-parenchymal cells following PHx.Conclusions
Liver regeneration following PHx is associated with significant changes in circulating LPA and hepatic LPAR1, LPAR3 and LPAR6 expression in a time- and cell-dependent manner. Furthermore, changes in LPA–LPAR post-PHx occur after the first round of hepatocyte division is complete. 相似文献10.