1,720,966 research outputs found
MRP-2 mediated biliary excretion but not renal function is a major determinant of exposure to mycophenolic acid acyl glucuronide
No full textDecrease in serum tacrolimus level and rise in serum creatinine under late addition of Cinacalcet in a renal transplant recipient with hyperparathyroidism: A case report
No full textCinacalcet is a calcimimetic drug that has been approved for treatment of secondary and tertiary hyperparathyroidism in patients with renal failure requiring renal replacement therapy. A few cases of successful treatment in renal transplant patients immunosuppressed with cyclosporine have been reported. Herein we have reported the case of a 48-year-old renal transplant recipient presenting with secondary hypercalcemic hyperparathyroidism (parathyroid hormone [PTH] 896 pg/mL; total calcium, up to 3.3 mmol/L) under immunosuppressive therapy with tacrolimus. Owing to substantial comorbidity and a high operative risk, we decided to initiate a therapeutic trial with cinacalcet. Using a daily dose of 30 mg of Cinacalcet, normal calcium levels and a mild fall in PTH levels (decline of 62 pg/mL) were achieved within the first week of treatment. At this point, we also observed a marked decrease in tacrolimus levels (from 6.3 to 2.6 mg/dL) without any change in concomitant medications. Thus, we adapted the tacrolimus dosage. Concurrent with cinacalcet therapy, there was a rise in serum creatinine levels (from 3.9 to 4.9 mg/dL before discontinuation of cinacalcet), which was not reversible after termination of 3 weeks of treatment with cinacalcet, but continued. Cinacalcet and tacrolimus are both metabolized via cytochrome P 450. The documented decrease in tacrolimus serum levels, suggested a drug- drug interaction between tacrolimus and cinacalcet. The irreversible deterioration in renal function may be attributed to nephrotoxic properties of cinacalcet, but may also indicate an acceleration of the natural course of chronic allograft nephropathy
MRP-2 mediated biliary excretion but not renal function is a major determinant of exposure to mycophenolic acid acyl glucuronide
No full textRapid detection of ITPA 94C > A and IVS2+21A > C gene mutations by real-time fluorescence PCR and in vitro demonstration of effect of ITPA IVS2+21A > C polymorphism on splicing efficiency
No full textAmpliChip CYP450 GeneChip (R): A new gene chip that allows rapid and accurate CYP2D6 genotyping
No full textMethods for Cytochrome P450-2D6 (CYP2D6) genotyping are often time-consuming and laborious, which can restrict their use in pretherapeutic screening programs. Gene chip technology could overcome this problem. The aim of this study was to evaluate CYP2D6 genotyping by a new improved gene chip compared to a PCR-RFLP method. AmpliChip CYP450 GeneChip (R) (AmpliChip) is a microarray hybridization method for genotyping CYP2D6 and CYP2C19. One hundred fifty-nine DNA samples were genotyped both by AmpliChip as well as by PCR-RFLP and, where applicable, by a SNaPshot technique which detects single nucleotide polymorphisms based on the single base extension principle. In 152 of the 159 samples, CYP2D6 genotypes determined with the AmpliChip were in accordance with the results of PCR-RFLP. All seven discrepant samples had gene duplications and were subjected to SNaPshot analysis. SNaPshot results concurred with those of the AmpliChip for six out of seven samples. In the one divergent result, DNA sequencing confirmed that the AmpliChip had assigned the correct genotype. In conclusion, AmpliChip is a highly reliable method for CYP2D6 genotyping that allows the correct determination of all relevant CYP2D6 alleles in one single run. It therefore represents a very efficient and fast method, offering new perspectives for the application of pharmacogenetics in clinical medicine
Assessment of amplichip CYP450 based CYP2D6-genotyping and phenotype prediction compared to PCR-RFLP-geno-typing and phenotyping by metoprolol pharmacokinetics
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Effect of the antioxidant idebenone on adverse events under mycophenolate mofetil therapy in a rat model
No full textBackground. Diarrhea and anemia are side effects of mycophenolic acid (MPA), but underlying mechanisms are not fully understood. Gene expression of major-alpha-hemoglobin and catalase was suppressed in livers of mycophenolate mofetil (MMF)-treated rats, suggesting MPA attenuates cellular defense against reactive oxygen species (ROS). We investigated whether the antioxidant idebenone might alleviate MPA-related side effects. Methods. Rats were treated as follows: group 1: controls; group 2: idebenone; group 3: MMF; and group 4: MMF/idebenone. Blood was collected weekly to determine cell counts, hemoglobin, MPA, plasma albumin, total protein, creatinine, and urea concentrations. On day 28 RNA was extracted from liver, kidneys, and bone marrow (BM). Colon and jejunum were examined histologically. Results. High-dose MMF-treated rats developed diarrhea, dehydration, and weight loss. After a week, a significant decrease (P=0.001) in erythrocyte count and hemoglobin concentration was observed that was not influenced by idebenone. Degenerative changes in the jejunum were slightly attenuated by idebenone. Idebenone did not influence MPA-induced suppression of catalase. A significant suppression of major-alpha-hemoglobin and the erythropoietin (EPO)-receptor in BM of MMF-treated groups and almost complete absence of hemopoietic progenitor cells were observed. EPO-mRNA was markedly upregulated in the MMF-group and even more in the MMF/idebenone-group. Conclusion. Idebenone showed minimal benefit on MMF-related diarrhea and anemia. BM of MMF-treated rats revealed erythroid aplasia as a possible reason for anemia. Marked upregulation of EPO-mRNA presumably reflects a compensatory mechanism. Because ROS have the potential to suppress EPO expression, it can be hypothesized that enhanced EPO-mRNA expression in MMF/idebenone-treated rats is caused by antagonism of ROS
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
