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101.
S Fletcher RG Jones HC Rayner P Harnden LD Hordon JE Aaron B Oldroyd AM Brownjohn JH Turney MA Smith 《Canadian Metallurgical Quarterly》1997,75(4):412-419
Bone biopsies were studied in 73 patients to determine if a two-site radioimmunometric assay for serum bone alkaline phosphatase (BAP), total serum alkaline phosphatase (ALP), serum intact parathyroid hormone (iPTH), hand X-rays, regional bone mineral density (BMD) measurements and parathyroid enlargement detected by ultrasonography could accurately predict renal osteodystrophy. In the patients studied 57 had hyperparathyroid bone disease, 4 mixed renal osteodystrophy, 3 adynamic bone disease, 1 osteomalacia and 8 normal histology. Serum BAP, ALP and iPTH correlated positively with mineral apposition rate, osteoblastic, osteoid and eroded surface. In the diagnosis of hyperparathyroid bone disease serum iPTH was the most sensitive investigation, detecting 81% of patients at a level > 100 pg/ml but with a specificity of only 66%. Serum BAP was more sensitive, 70% at a level of > 10 ng/ml, than serum total ALP, 30% at a level of 300 IU/l, with similar specificities, 92 and 100%, respectively. Ultrasound detection of an enlarged parathyroid gland had a sensitivity of 64% and a specificity of 100% for the diagnosis of hyperparathyroid bone disease. Hand X-rays had a poor sensitivity, 47%, but a high specificity, 92%, for the detection of hyperparathyroid bone disease. The majority of patients had regional BMD values within the normal reference range and this test was of poor discriminatory value. The non-invasive markers were unable to distinguish between patients with low turnover, mild hyperparathyroidism and patients with normal histology. In conclusion the measurement of serum iPTH is a useful screening tool for the detection of hyperparathyroid bone disease which can be confirmed by the finding of a raised serum BAP or parathyroid enlargement. For definitive diagnosis, however, the gold standard remains bone biopsy and at present one cannot recommend any non-invasive method as an adequate substitute. 相似文献
102.
JM Herbert JP Hérault A Bernat RG van Amsterdam JC Lormeau M Petitou C van Boeckel P Hoffmann DG Meuleman 《Canadian Metallurgical Quarterly》1998,91(11):4197-4205
SANORG 34006 is a new sulfated pentasaccharide obtained by chemical synthesis. It is an analog of the "synthetic pentasaccharide" (SR 90107/ ORG 31540) which represents the antithrombin (AT) binding site of heparin. SANORG 34006 showed a higher affinity to human AT than SR 90107/ORG 31540 (kd = 1.4 +/- 0.3 v 48 +/- 11 nmol/L), and it is a potent and selective catalyst of the inhibitory effect of AT on factor Xa (1,240 +/- 15 anti-factor Xa U/mg v 850 +/- 27 anti-factor Xa U/mg for SR 90107/ORG 31540). In vitro, SANORG 34006 inhibited thrombin generation occurring via both the extrinsic and intrinsic pathway. After intravenous (IV) or subcutaneous (SC) administration to rabbits, SANORG 34006 displayed a long-lasting anti-factor Xa activity and inhibition of thrombin generation (TG) ex vivo. SANORG 34006 was slowly eliminated after IV or SC administration to rats, rabbits, and baboons, showed exceptionally long half-lives (between 9.2 hours in rats and 61.9 hours in baboons), and revealed an SC bioavailability near 100%. SANORG 34006 displayed antithrombotic activity by virtue of its potentiation of the anti-factor Xa activity of AT. It strongly inhibited thrombus formation in experimental models of thromboplastin/stasis-induced venous thrombosis in rats (IV) and rabbits (SC) (ED50 values = 40.0 +/- 3.4 and 105.0 +/- 9.4 nmol/kg, respectively). The duration of its antithrombotic effects closely paralleled the ex vivo anti-factor Xa activity. SANORG 34006 enhanced rt-PA-induced thrombolysis and inhibited accretion of 125I-fibrinogen onto a preformed thrombus in the rabbit jugular vein suggesting that concomitant use of SANORG 34006 during rt-PA therapy might be helpful in facilitating thrombolysis and preventing fibrin accretion onto the thrombus under lysis. Contrary to standard heparin, SANORG 34006 did not enhance bleeding in a rabbit ear incision model at a dose that equals 10 times the antithrombotic ED50 in this species and, therefore, exhibited a favorable therapeutic index. We suggest that SANORG 34006 is a promising compound in the treatment and prevention of various thrombotic diseases. 相似文献
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D Lau BJ Hering A El-Ouaghlidi H Jahr H Brandhorst D Brandhorst R Vietzke K Federlin RG Bretzel 《Canadian Metallurgical Quarterly》1999,77(1):175-177
The shikimate pathway presents an attractive target for malaria chemotherapy. Three shikimic acid analogs exhibited different effects on Plasmodium falciparum growth. (6R)-6-Fluoro-shikimate and (6S)-6-fluoro-shikimate inhibited growth (50% inhibitory concentrations, 1.5 x 10(-5) and 2.7 x 10(-4) M, respectively), whereas 2-fluoro-shikimate had no effect. para-Aminobenzoic acid abrogated the inhibition, demonstrating that the shikimate pathway was specifically targeted. 相似文献
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JT Green GA Thomas J Rhodes BK Evans MA Russell C Feyerabend GS Fuller RG Newcombe WJ Sandborn 《Canadian Metallurgical Quarterly》1997,61(3):340-348
BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis. 相似文献
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