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41.
Julia C Wessel Magdalena Matyja Michael Neugebauer Heiko Kiefer Thomas Daldrup Fuad A Tarbah Horst Weber 《European journal of pharmaceutical sciences》2006,28(1-2):15-25
Metamizol (dipyrone, 1), a widely used drug with effective analgesic and antispasmodic properties, shows severe side effects like agranulocytosis and anaphylactic shock reactions, the reasons of which are not known until today. After oral administration 1 is completely metabolized. All hitherto known metabolites have an intact pyrazolinone ring structure like the parent compound and are completely extractable from urine with polar organic solvents. However, only a fractional amount of the applied dosage can be recovered by this procedure. To clarify the reason of this deficit of unknown metabolites we followed the hypothesis of oxidative rupture of the heterocyclic ring during metabolism of 1. On the basis of former in vitro results we now were able to identify in quality three oxalic acid derivatives and one acetic acid phenylhydrazide as new metabolites of metamizol in the allantoic fluid (AF) of incubated hen's eggs as well as in human urine by means of GC-MS analysis and comparison with unequivocally synthesized authentic reference compounds. Whereas the oxamazide 7, the phenylhydrazide 8 and N-methyloxamic acid 9 are only present in trace concentrations and therefore cannot account for the deficit in the balance of metabolites, the oxalic acid monohydrazide 11 seems to be excreted in higher amount. But quantitative determination of this new metabolite would be required to answer the open questions concerning the biotransformation of metamizol and thereby to detect new facts about mode of action and side effects of this drug. 相似文献
42.
Does bioequivalence between modified cyclosporine formulations translate into equal outcomes? 总被引:2,自引:0,他引:2
Taber DJ Baillie GM Ashcraft EE Rogers J Lin A Afzal F Baliga P Rajagopalan PR Chavin KD 《Transplantation》2005,80(11):1633-1635
Neoral was replaced with a generic cyclosporine formulation on our hospital formulary. We compared outcomes for de novo kidney transplant recipients who either received Gengraf (n=88) or Neoral (n=100) in a single-center, retrospective review. As compared to patients who received Neoral, patients who received Gengraf were significantly more likely to have an acute rejection episode (39% vs. 25%, P=0.04), more likely to have a second rejection episode (13% vs. 4%; P=0.03), or to have received an antibody preparation to treat acute rejection (19% vs. 8%; P=0.02). Patients treated with Gengraf had a higher degree of intrapatient variability for cyclosporine trough concentrations as determined by %CV (P<0.05). The incidence of acute rejection at 6 months posttransplant was significantly higher in patients who received Gengraf compared to Neoral. A larger, prospective analysis is warranted to compare these formulations of cyclosporine in de novo kidney transplant recipients. 相似文献
43.
From the periphery of the glomerular capillary wall toward the center of disease: podocyte injury comes of age in diabetic nephropathy 总被引:41,自引:0,他引:41
Nephropathy is a major complication of diabetes. Alterations of mesangial cells have traditionally been the focus of research in deciphering molecular mechanisms of diabetic nephropathy. Injury of podocytes, if recognized at all, has been considered a late consequence caused by increasing proteinuria rather than an event inciting diabetic nephropathy. However, recent biopsy studies in humans have provided evidence that podocytes are functionally and structurally injured very early in the natural history of diabetic nephropathy. The diabetic milieu, represented by hyperglycemia, nonenzymatically glycated proteins, and mechanical stress associated with hypertension, causes downregulation of nephrin, an important protein of the slit diaphragm with antiapoptotic signaling properties. The loss of nephrin leads to foot process effacement of podocytes and increased proteinuria. A key mediator of nephrin suppression is angiotensin II (ANG II), which can activate other cytokine pathways such as transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF) systems. TGF-beta1 causes an increase in mesangial matrix deposition and glomerular basement membrane (GBM) thickening and may promote podocyte apoptosis or detachment. As a result, the denuded GBM adheres to Bowman's capsule, initiating the development of glomerulosclerosis. VEGF is both produced by and acts upon the podocyte in an autocrine manner to modulate podocyte function, including the synthesis of GBM components. Through its effects on podocyte biology, glomerular hemodynamics, and capillary endothelial permeability, VEGF likely plays an important role in diabetic albuminuria. The mainstays of therapy, glycemic control and inhibition of ANG II, are key measures to prevent early podocyte injury and the subsequent development of diabetic nephropathy. 相似文献
44.
Complement fixing (CF) antibody titers to measles, parainfluenza (PI) types I and 3, mumps, herpes type 1, and cytomegalovirus (CMV) in serum and cerebrospinal fluid (CSF) of 33 patients with subacute sclerosing panencephalitis (SSPE) were evaluated. Results were analyzed in comparison to 11 patients with neurological diseases other than SSPE and 7 normal subjects. All SSPE patients had elevated serum and CSF measles antibody titers. The number of SSPE patients manifesting elevated titers other than measles did not reach statistical significance when compared to controls, except for PI type 1. This suggests a possible dual infection with measles and PI in SSPE. The anticomplementary effect detected in the serum and CSF of some patients indirectly suggests the presence of immune complexes. 相似文献
45.
46.
Ascites often contributes to patient morbidity and discomfort. When refractory to medical management, it has been managed with repeated paracentesis, implantable ports for drainage, or diversion to the urinary bladder. Peritoneovenous shunt insertion has been a technique that was traditionally performed only by surgeons but is now within the realm of interventional radiologists. Its advantage is that protein-rich ascitic fluid is returned to the intravascular compartment. This retrospective study elaborates on the successes and problems encountered during shunt insertion in our first 13 patients. Two patients are well with a functioning shunt at 14 and 32 weeks. In 6 the shunt functioned until the patients death from the underlying malignancy. Two required revision with variable success and in 2, shunt function could not be salvaged. There was one procedure-related mortality. Radiological insertion of these shunts is feasible and should be considered for selected patients. Options are available for assessment and salvaging of dysfunctional shunts. 相似文献
47.
Boughey JC Emovon OE Afzal F Baliga P Rogers J Lin A Chavin K Rajagopalan PR 《Clinical transplantation》2004,18(3):336-338
Pelvic kidneys are uncommon anomalies rarely utilized in kidney transplantation. We describe a successful case of living-donor transplantation using a pelvic kidney in a 17-month-old infant with congenital renal dysplasia. The recipient had exhausted all options for renal replacement therapy, and urgent transplantation was considered a life saving treatment. 相似文献
48.
Lechin F Van Der Dijs B Lechin AE 《Clinical science (London, England : 1979)》2002,103(4):345; author reply 346
49.
50.
Todd AC Carroll S Geraghty C Khan FA Moshier EL Tang S Parsons PJ 《Physics in medicine and biology》2002,47(8):1399-1419
This study aimed to quantify the accuracy and precision of a method for in vivo measurements of lead in bone using L-shell x-ray fluorescence (LXRF), the former via comparison with independent measurements of lead in bone obtained using electrothermal atomic absorption spectrometry (AAS) following acid digestion. Using LXRF. the lead content of adult human cadaver tibiae was measured, both as intact legs and as dissected tibiae with overlying tissue removed, the latter at several proximal-distal locations. After LXRF, each tibia was divided into nine cross-sectional segments, which were further separated into tibia core and surface samples for AAS measurement. The proximal-distal variability of AAS-measured core and surface tibia lead concentrations has been described elsewhere (the lead concentration was found to decrease towards both ends of the tibia). The subjects of this paper are the proximal-distal variability of the LXRF-measured lead concentrations, the measurement uncertainty and the statistical agreement between LXRF and AAS. There was no clear proximal-distal variability in the LXRF-measured concentrations; the degree of variability in actual tibia lead concentrations is far less than the LXRF measurement uncertainty. Measurement uncertainty was dominated by counting statistics and exceeded the estimate of lead concentration in most cases. The agreement between LXRF and AAS was reasonably good for bare bone measurements but poor for intact leg measurements. The variability of the LXRF measurements was large enough, for both bare bone and intact leg measurements, to yield grave concerns about the analytical use of the technique in vivo. 相似文献