Chemical Proteomics-Based Analysis of Off-target Binding Profiles for Rosiglitazone and Pioglitazone: Clues for Assessing Potential for Cardiotoxicity

Drugs exert desired and undesired effects based on their binding interactions with protein target(s) and off-target(s), providing evidence for drug efficacy and toxicity. Pioglitazone and rosiglitazone possess a common functional core, glitazone, which is considered a privileged scaffold upon which to build a drug selective for a given target—in this case, PPARγ. Herein, we report a retrospective analysis of two variants of the glitazone scaffold, pioglitazone and rosiglitazone, in an effort to identify off-target binding events in the rat heart to explain recently reported cardiovascular risk associated with these drugs. Our results suggest that glitazone has affinity for dehydrogenases, consistent with known binding preferences for related rhodanine cores. Both drugs bound ion channels and modulators, with implications in congestive heart failure, arrhythmia, and peripheral edema. Additional proteins involved in glucose homeostasis, synaptic transduction, and mitochondrial energy production were detected and potentially contribute to drug efficacy and cardiotoxicity

Surgical Treatment of Iliofemoral Vein Thrombosis in Pregnancy

The incidence of deep leg vein thrombosis in pregnancy is estimated at 0.13 per 1000 to 1.4 per 100.1−3 One-third occur as isolated, descending iliofemoral vein thromboses, predominantly left-sided. We report our surgical experiences in venous thrombectomy with arteriovenous fistula (AV-fistula) in the groin between the superficial femoral artery and femoral vein in 29 gravidae with a mean age of 27.5 years (range 19–41 years). Thrombosis occurred between the 20th and 36th week of pregnancy. 25 were antepartum two postpartum and two postsectionem. An iliac spur was seen once, as was an AT III deficiency. At the beginning of our series AV-fistula was not performed in three patients who all suffered from re-thrombosis after 24 h. Re-thrombectomy with an AV-fistula was performed successfully. Three of the 26 gravidae with AV-fistula also developed re-thrombosis. In two patients re-thrombectomy was successful, in the third patient the common iliac vein could not be re-opened by thrombectomy and the functioning AF-fistula had been ligated because extensive vulval oedema had developed. Asymptomatic, late re-thrombosis occurred in two patients who were seen at outpatient follow-up. We have seen one mild, non-life-threatening pulmonary embolism on the first postoperative day. No further intraoperative nor postoperative or postpartum complications developed. The re-occlusion rate is 10.3% (3/29), the complication rate is 6.9% (2/29). </jats:p