Interactions of human organic anion transporters 1-4 and human organic cation transporters 1-3 with the stimulant drug methamphetamine and amphetamine.

Drug membrane transport system proteins, namely, drug transporters, are expressed in the kidney and liver and play a crucial role in the excretion process. This study aimed to elucidate the interactions of the drug transporters human organic anion transporters 1, 2, 3, 4 (hOAT1, 2, 3, 4) and human organic cation transporters 1, 2, 3 (hOCT1, 2, 3), which are expressed primarily in human kidney, liver, and brain, with the stimulants methamphetamine (METH) and amphetamine (AMP). The results of an inhibition study using representative substrates of hOATs and hOCTs showed that METH and AMP significantly inhibited (by >50%) uptake of the hOCT1 and hOCT3 representative substrate 1-methy1-4-phenylpyridinium ion (MPP+) and hOCT2 representative substrate tetraethyl ammonium (TEA). However, METH and AMP did not inhibit uptake of the representative substrates of hOAT1, hOAT2, hOAT3, and hOAT4, (i.e., p-aminohippuric (PAH) acid, prostaglandin F2α (PGF2α), estron sulfate (ES), and ES respectively). Kinetic analyses revealed that METH competitively inhibited hOCT1-mediated MPP+ and hOCT2-mediated TEA uptake (Ki, 16.9 and 78.6 µM, respectively). Similarly, AMP exhibited competitive inhibition, with Ki values of 78.6 and 42.8 µM, respectively. In contrast, hOCT3 exhibited mixed inhibition of representative substrate uptake; hence, calculating Ki values was not possible. Herein, we reveal that hOCTs mediate the inhibition of METH and AMP. The results of this uptake study suggest that METH and AMP bind specifically to hOCT1 and hOCT2 without passing through the cell membrane, with subsequent passage of METH and AMP via hOCT3.

Abdominal Stab Wounds with Tension Pneumopericardium Confirmed by Autopsy and Postmortem Computed Tomography.

We present the first report of pneumopericardium observed by autopsy and on postmortem computed tomography (PMCT) images. The subject was a woman who died of self-inflicted stab wounds to the abdomen. The PMCT scan revealed air in the pericardial sac, a "flattened heart" sign, and retroperitoneal hemorrhage. Medicolegal autopsy revealed two abdominal stab wounds near the xiphoid process that had cut the apical pericardium and adjacent diaphragm and liver. Examination of the open thorax confirmed that the pericardial sac was distended with air. The wound extended to the abdominal aorta, causing retroperitoneal hemorrhage. PMCT images showed that the pneumopericardial volume was 133 mL. We believe that cardiac tamponade occurred resulting from the tension pneumopericardium; however, the effects were mitigated by hypovolemia secondary to the retroperitoneal hemorrhage as well as obstructive shock. Therefore, the cause of death appears to have been low-pressure cardiac tamponade.