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  • Nephrotoxicity  (2)
  • Dipeptidyl aminopeptidase IV  (1)
  • Hyperlipidaemia  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Clinica Chimica Acta 179 (1989), S. 61-71 
    ISSN: 0009-8981
    Keywords: Dipeptidyl aminopeptidase IV ; Human kidney ; Purification
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Hyperlipidaemia ; Cholesterol ; Triglycerides ; Uraemia ; Regular haemodialysis treatment ; Bezafibrate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hyperlipidaemia may contribute to the high rate of cardiovascular complications in patients on chronic haemodialysis (CHD). However, possibilities of lipid lowering therapy in CHD are still limited. The applicability of bezafibrate (BF), a recently developed clofibrate analogue, was investigated in patients on CHD with triglyceride and/or total cholesterol levels above 300 mg/dl. The lipid lowering effect was studied in a placebo-controlled trial over 6 months in 19 patients. Long-term effect was followed in six patients over a mean period of 29 months. Elimination half-life and mean therapeutic serum concentration were calculated by 72-h BF serum profiles, obtained after the first drug administration of a single 200-mg dose and during steady state after 12 weeks of treatment. Elimination half-lives were 17 h at start and 22 h after 12 weeks compared with 2 h in subjects with normal renal function. Dose reduction to 200 mg every 3rd day was necessary and resulted in a mean therapeutic serum concentration of 3.4 mg/l, which was similar to 3.0 mg/l of normal subjects, who received the dose optimal for lowering of lipids (200 mg 3 × /day). The protein-bound serum fraction of BF was decreased to 8% in CHD patients, compared with 95% found in normal subjects. BF therapy resulted in a marked reduction of serum triglycerides from 478 mg/dl by 31% and total cholesterol levels from 311 mg/dl by 19% as well as β-Lp-cholesterol from 178 mg/dl by 17%, whereas the initially low α-Lp-cholesterol increased significantly from 18,3 mg/dl by 58%. Under long-term therapy not only continuously low triglyceride and cholesterol levels could be maintained, moreover a further decline (−20% and −7%) could be achieved. Safety laboratory controls, comprising haemoglobin, bilirubin, liver enzymes, CK and albumin, showed no significant changes apart from a slight reversible increase in CK and a decrease in gamma-GT and alkaline phosphatase. Subjective side effects were not reported. Under this dosage schedule, BF therapy was thus effective and safe, improving potentially atherogenic disturbances of lipid metabolism.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. S33 
    ISSN: 1432-1041
    Keywords: Nephrotoxicity ; Cell repair ; drug induced nephrotoxicity ; growth factors ; specific proteinuria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nephrotoxic drugs may account for approximately at least 20 % of clinically observed cases of acute renal failure in whom tubular lethal or sublethal damage is a predominant finding. Acute toxic tubular cell injury is characterized by loss of cellular polarization, intrinsic energy deficiency, calcium overload, release of toxic proteases and free oxygen radicals, derangement of the cytoskeleton, and vacuolar transformation of brush border microvilli. These events may finally lead to irreversible cell death. Shedding of membrane enzymes and cytoskeletal components in urine (kidney tissue proteinuria) may serve as a noninvasive early marker for assessing tubular cell injury. Successful recovery of renal function depends on early repair of lethally or sublethally damaged nephrons, in which intrinsic nephrogenic adaptive and proliferative responses cooperate in concert with auto/para/-juxtacrine growth promoting factors and cytokines. Exogenously administered growth factors may enhance renal cell recovery, as shown in animal models. Increased expression of immediate early genes in tubular cells after renal injury reflects the ongoing mitogenic activity necessary for reepithelialization and remodeling (new, polarized, differentiated cells). Further progress in understanding the molecular mechanisms of renal tubular injury will probably influence the diagnostic modalities and therapeutic approaches to acute drug induced renal failure.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: Nephrotoxicity ; cephamandol ; cephazolin ; cephacetrile ; cephalothin ; brush border enzymes ; urine alanine-aminopeptidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cephamandol 6.0 g, cephazolin 6.0 g or cephacetrile or cephalothin 8.0 g were administered as short-term infusions on 3 consecutive days to informed volunteers, who had no history or evidence of impairment of renal funktion. There were 15 subjects in the cephamandol, cephacetrile and cephalothin groups and 14 subjects in the cephazolin group. Alanine-aminopeptidase, a characteristic tubule enzyme, was determined in a 24-hour urine 2 days before administration, during the 3 day administration and on the 4 subsequent days. In addition, alanine-aminopeptidase was also estimated immunologically in concentrated urine with the aid of an anti-brush border antibody. Cephamandol, cephazolin and cephalothin were completely without effect on the proximal tubule. Cephacetrile, on the other hand, showed clear reactions in 9 out of 15 subjects, in the form of elevated AAP activity in urine and in 6 of the cases membrane elimination was demonstrable immunologically. After withdrawal of the medication, the values of the responder group returned spontaneously to normal, i. e. no cumulative effect was detected. These investigations show that elimination of alanine-aminopeptidase in the urine is a very sensitive index of the action of cephalosporins on renal tubules.
    Type of Medium: Electronic Resource
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