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Tudor Andrew M. Church Steven J. Hendra Patrick J. Davies Martyn C. Melia Colin D. 《Pharmaceutical research》1993,10(12):1772-1776
We analyzed binary mixtures of polymorphs A and B of chlorpropamide ((l-[4-chlorobenzenesulphonyl]-3-propyl urea)) by near-infrared Fourier transform Raman spectroscopy (FTRS). The individual polymorphs were prepared and characterized by differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) microscopy, and physical appearance. The FTR spectra of the two polymorphs showed distinct differences which result from "crystal splitting effects. A series of 13 different mixtures of polymorph A and B was prepared by geometric mixing and their FTR spectra statistically analysed by factor analysis programming. Predictions of the A/B polymorphic composition of mixtures were made and compared with the theoretical values. The results demonstrate that FTRS combined with factor analysis programming may be successfully applied to the in situ monitoring of the A/B polymorphic nature of a chlorpropamide sample. 相似文献
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An algorithm has been developed to provide predictable control of blood glucose for 48 h following acute myocardial infarction. In 29 diabetic patients intravenous infusion of soluble insulin was started upon admission to hospital and the rate adjusted hourly on the basis of bedside capillary glucose estimations. Insulin infusion rates related to glycaemia were higher in obese patients and those with severe cardiac failure. For all patients mean admission glucose levels were reduced from 18.3 +/- 5.9 mmol l-1 to 9.1 +/- 3.3 mmol l-1 at 4 h and to 8.8 +/- 2.5 mmol l-1 at 6 h. Mean glucose concentrations for 48 h after admission were 8.2 +/- 1.3 mmol l-1 for all patients. Admission glucose levels were slightly higher in patients with severe, compared to those without or mild, cardiac failure (P less than 0.1), but levels over the following 48 h were similar. Doubling insulin infusion rates before meals did not achieve tighter glycaemic control. Hypoglycaemia (glucose less than 3 mmol l-1) occurred on 11 occasions in six patients; only two episodes were symptomatic and only two episodes occurred when the insulin rates were doubled before meals. This algorithm produced tighter glycaemic control than previously published protocols, particularly in patients with severe cardiac failure. Hypoglycaemia is uncommon and the algorithm easy to administer by nursing staff. 相似文献
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Genomic Understanding Reveals the Important Role of FGFR2 as Paeoniflorin Target for Circumventing Breast Cancer Resistance to Tamoxifen
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Moh Arikus WibowoEri Prasetyo NugrohoAdam Hermawan 《Asian Pacific journal of cancer prevention》2021,22(12):3949-3958
Objectives: Paeoniflorin (PF), a compound found in Paeonia lactiflora and Paeonia suffruticosa, has anticancer potential, particularly in inhibiting migration and invasion, the resistant cancer cells hallmarks. To date, the mechanism of overcoming tamoxifen resistance in breast cancer is not yet elucidated. This research aims to explore the potential target of PF as a co-treatment for circumventing breast cancer resistance to tamoxifen with a genomic understanding-bioinformatics. Methods: Microarray data originating from GSE67916 and GSE85871 in the NCBI GEO database was analyzed to obtain differentially expressed genes (DEGs). Further analyses were performed on DEGs using the DAVID v6.8, STRING-DB v11.0, the Cytoscape, and cBioportal. Gene expression analysis validation in breast cancer cells and tamoxifen-resistant breast cancer cells was accomplished using GEPIA and ONCOMINE databases. Survival rate analysis of selected genes was conducted using Kaplan–Meier. Results: We obtained 175 DEGs from the two samples (tamoxifen-resistant and paeoniflorin-treated). DEG involves in 70 biological processes, 26 cellular components, and 18 molecular functions, and three pathways relevant to breast cancer. The PPI network analysis and hub genes selection obtained 10 genes with the highest degree scores. Genetic changes for selected genes, including IFNB1, CDK6, FGFR2, OAS1, BCL2, and STAT2 were found from 0.5% to 7% of the case population per patient case. Additional analysis using cBioportal revealed FGFR signaling pathway through Ras is important for the PF mechanism in circumventing breast cancer resistance to tamoxifen. ONCOMINE and GEPIA analysis emphasized the importance of selected genes in the tamoxifen-resistance mechanism. Conclusion: PF has potential to be used as a co-treatment for circumventing breast cancer resistance to tamoxifen by targeting FGFR2 signaling, but further validation is needed. 相似文献
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There are conflicting reports of platelet function abnormalities in diabetic patients without vascular complications. We have studied in vitro platelet aggregation, using platelet rich plasma and whole blood techniques, in 18 patients with uncomplicated insulin-dependent diabetes and a matched group of 24 non-diabetic subjects. In addition we measured plasma beta-thromboglobulin levels in these groups, as an index of in vivo platelet activation, and compared the indices of in vitro and in vivo platelet function before and after maximal bicycle exercise. Before exercise plasma beta-thromboglobulin levels and platelet sensitivities to ADP, collagen or adrenaline, as assessed by both methods of platelet aggregation, were the same in diabetic and control subjects. Both groups showed similar increases in beta-thromboglobulin levels and in platelet sensitivity to all agonists in whole blood following exercise. Using platelet rich plasma there were no changes in platelet sensitivity in either group after exercise. In non-diabetic subjects, increases in noradrenaline levels after exercise correlated with increases in platelet sensitivity to adrenaline in whole blood. This was not observed in the diabetic group. Abnormalities of platelet function, using the techniques described here, are not present in diabetic patients who do not have clinical evidence of vascular disease. 相似文献
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Orbital irradiation for Graves' ophthalmopathy: Is it safe? A long-term follow-up study 总被引:4,自引:0,他引:4
Wakelkamp IM Tan H Saeed P Schlingemann RO Verbraak FD Blank LE Prummel MF Wiersinga WM 《Ophthalmology》2004,111(8):1557-1562
PURPOSE: We evaluated the frequency of long-term complications of orbital irradiation (radiation-induced tumors, cataract, and retinopathy) in comparison with glucocorticoids. DESIGN: We conducted a follow-up study in a cohort of 245 Graves' ophthalmopathy patients who had been treated with retrobulbar irradiation (20 Gy in 2 weeks) and/or oral glucocorticoids between 1982 and 1993 in our institution. Irradiated patients were compared with nonirradiated patients. METHODS: Data on mortality and cause of death were obtained. Living patients were invited to participate in a follow-up study. Possible retinopathy was assessed in a masked fashion and defined as the presence of > or =1 hemorrhages and/or microaneurysms on red-free retina photographs. If >5 lesions were present, patients were categorized as suffering from definite retinopathy. Cataract was assessed using the Lens Opacity Classification System II score. MAIN OUTCOME MEASURES: Mortality, prevalence of retinopathy, prevalence of cataract, and type of cataract. RESULTS: Thirty-seven of the 245 patients had died, none of them from an intracranial tumor. Mortality was similar in the irradiated (27/159 [17%]) and nonirradiated patients (10/86 [12%]; P = 0.264). One hundred fifty-seven of the 208 living patients (75%) consented to participate in a follow-up ophthalmologic investigation; the mean follow-up time (+/- standard deviation) was 11+/-3 years. Possible retinopathy was present in 15% of patients, 22 of the irradiated and 1 of the nonirradiated patients (P = 0.002). In 5 patients (all had been irradiated), definite retinopathy (i.e., >5 retinal lesions) was present. Of these, 3 had diabetes mellitus, and 1 had hypertension. Diabetes was associated with both possible (P = 0.029) and definite (P = 0.005) retinopathy, with a relative risk of 21 (95% confidence interval, 3-179). The prevalence and severity of cataract were similar in the radiotherapy group (29%) and the glucocorticoid group (34%); it should be noted that 88 of 104 of the irradiated patients were also treated with oral glucocorticoids. CONCLUSION: The data suggest that orbital irradiation for Graves' ophthalmopathy is a safe treatment modality, except possibly for diabetic patients. 相似文献
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Watts Peter J. Tudor Andrew Church Stephen J. Hendra Patrick J. Turner Paul Melia Colin D. Davies Martyn C. 《Pharmaceutical research》1991,8(10):1323-1328
FT-Raman spectroscopy (FTRS) has been used to characterize microspheres produced from the pharmaceutical polymer Eudragit RS containing a range of concentrations of the drug sulfasalazine. While pure sulfasalazine produced an intense and complex Raman spectrum, the spectrum of drug-free Eudragit RS microspheres was considerably weaker in intensity and contained only a few prominent Raman scattering peaks. In spectra of the drug–polymer micro-spheres, peaks arising from the individual components could be identified. This enabled a quantitative analysis to be undertaken by calculating the ratio between the area of a sulfasalazine peak and the area of a Eudragit RS peak for each microsphere spectrum. A correlation was shown between the peak area ratio and the microsphere sulfasalazine content. FTRS was then applied to a series of microsphere samples which had been dissoluted into pH 7 buffer for 1, 3, 6, 9, 12, or 24 hr. For each spectrum, the drug-polymer peak area ratio was determined and this in turn enabled calculation of the residual drug content of the microsphere sample. FTRS-calculated data showed good agreement with microsphere drug content values determined spectrophotometrically. 相似文献