Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) The standard anticoagulant therapy for prevention of thrombosis after hip or knee replacement surgery is subcutaneous injection of a low-molecular-weight heparin, such as enoxaparin; (2) Rivaroxaban is an oral factor-Xa inhibitor anticoagulant approved for use in these indications in the European Union; (3) Four double-blind controlled trials in more than 12 000 patients undergoing hip or knee replacement surgery failed to show that rivaroxaban was any more effective than enoxaparin on relevant clinical outcomes; there was no reduction in mortality, nor in the incidence of pulmonary embolism and symptomatic deep venous thrombosis; (4) In the selected populations enrolled in these trials, the bleeding risk was similar in the rivaroxaban and enoxaparin groups. However, it is possible that very underweight or overweight patients have an increased bleeding risk with rivaroxaban; (5) More information is needed on the nephrotoxicity of rivaroxaban, and a risk of mitochondrial toxicity cannot be ruled out. Post-marketing studies also need to focus on the consequences of wound seepage, which is more frequent with rivaroxaban. (6) Rivaroxaban is metabolized by the cytochrome P450 isoenzyme CYP 3A4 and binds to P-glycoprotein, hence a high risk of pharmacokinetic interactions; (7) Rivaroxaban has the advantage of being an oral treatment that does not require laboratory monitoring. However, it seems best to monitor renal function. It should also be noted that there is no effective antidote if severe bleeding occurs; (8) In practice, for frail elderly patients, who are often polymedicated, it seems more prudent to continue using low-molecular-weight heparin, a drug with which we have more experience.
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PMID:Rivaroxaban: new drug. After hip or knee replacement surgery: LMWH is safer. 1974 67

Introduction: An increase of serum dehydroepiandrosterone (DHEA) sulfate (DHEAS) is observed in premature adrenarche and congenital adrenal hyperplasia. Very high DHEAS levels are typical for adrenal tumors. Approximately 74% of DHEAS is hydrolyzed to DHEA by the steroid sulfatase (STS). The reverse reaction is DHEA sulfation. Besides these two enzyme reactions, the DHEAS transported through the cell membrane is important for its distribution and excretion. Case Presentation: We present a female adolescent with overweight and a very high DHEAS. The presence of a DHEAS-producing tumor was rejected using ultrasonography, Magnetic Resonance Tomography (MRT), and dexamethasone suppression. STS deficiency was suspected. Sequence analysis revealed a heterozygous nonsense mutation which predicts a truncation of the carboxyl region of the STS that is implicated in substrate binding. No partial gene deletion outside exon 5 was detected by multiplex ligation-dependent probe amplification. The bioassay revealed normal enzyme activity in the patient's leukocytes. A defect of transporter proteins was suggested. Both efflux [multidrug-resistance protein (MRP)2 and breast cancer-resistance protein (BCRP)] and uptake [organic anion-transporting polypeptide (OATP) and organic anion transporter (OAT) carriers] transporters were studied. Sequence analysis of exons revealed a heterozygous Q141K variant for BCRP. Conclusions: A novel heterozygous nonsense mutation in the STS gene and a known heterozygous missense variant in the BCRP gene were found. The heterozygous nonsense mutation in the STS gene is not supposed to be responsible for STS deficiency. The BCRP variant is associated with reduced efflux transport activity only in its homozygous state. The combination of the two heterozygous mutations could possibly explain the observed high levels of DHEAS and other sulfated steroids.
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PMID:Very High Dehydroepiandrosterone Sulfate (DHEAS) in Serum of an Overweight Female Adolescent Without a Tumor. 3243 30