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To the Editor: Insomnia is a common disorder and public health burden. Frequently prescribed hypnotics enhance [gamma]-aminobutyric acid or block orexin signaling. With few pharmacological modalities and limitations associated with [...]

Plasma membrane monoamine transporter (PMAT) is a novel polyspecific organic cation transporter that transports organic cations and the purine nucleoside, adenosine. PMAT is expressed in the kidney, but the specific localization and function of this transporter in renal cells are unclear. In this study, we developed a polyclonal antibody toward a 14-amino acid sequence in the last intracellular loop of PMAT and determined the precise cellular localization of PMAT in human and rat kidneys. Surprisingly, we found that the PMAT protein was predominantly expressed in the glomerulus with minimal expression in tubular cells. Within the glomerulus, dual-color immunofluorescence labeling showed that the PMAT protein was specifically localized to the visceral glomerular epithelial cells, i.e., podocytes. There was no significant PMAT immunoreactivity in mesangial or glomerular endothelial cells. We further showed that puromycin aminonucleoside (PAN), a classic podocyte toxin that induces massive proteinuria and severe glomerulopathy, is transported by PMAT. Expression of PMAT in Madin-Darby canine kidney cells significantly increased cell sensitivity to PAN. Decynium 22, a potent PMAT inhibitor, abolished PAN toxicity in PMAT-expressing cells. Together, our data suggest that PMAT is specifically expressed in podocytes and may play an important role in PAN-induced kidney injury. [ABSTRACT FROM AUTHOR]

To explore the risk factors for venous thromboembolism (VTE) in inpatients with colorectal cancer. The demographic factors, comorbidities, and hematological indices of patients with colorectal cancer treated in our hospital from 2016 to 2021 were collected and recorded. Venous thromboembolism events, including deep venous thrombosis and/or pulmonary embolism, were recorded and the patients were divided into the VTE group and the non-VTE group. We compared clinical data between the two groups and explored risk factors for VTE. Comparing the clinical data of 293 cases of non-VTE group and 235 cases of VTE group, we found significant differences in age, smoking, temperature, amount of blood loss, differentiation degree, peripherally inserted central catheter (PICC), radiotherapy, anemia, infection, white blood cell count, prothrombin time (PT), PT%, prothrombin ratio, international normalized ratio, thrombin time, CA199 and CEA between the two groups ( P < 0.05). Logistic regression analysis showed that age ( P = 0.0444), temperature ( P = 0.0317), amount of blood loss ( P = 0.0067), PICC ( P < 0.0001), chemotherapy ( P = 0.0459), anemia ( P = 0.0007), international normalized ratio ( P = 0.003) and CA199 ( p = 0.0234) were independent risk factors for VTE. Receiver operating characteristic curve analysis showed that the amount of blood loss predicted thrombosis better (AUC = 0.778, P < 0.001), when the cutoff value was 20 mL, the sensitivity was 76.17%, and the specificity was 79.18%, respectively. And PICC predicted thrombosis better (AUC = 0.808, P < 0.001), the sensitivity was 70.21%, and the specificity was 91.47%, respectively. Clinical parameters are associated with VTE in inpatients with colorectal cancer, which will help to guide clinicians to take effective measures to improve the patients' prognosis., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Plasma membrane monoamine transporter (PMAT) is a novel membrane transporter recently cloned and characterized in our laboratory. We previously demonstrated that PMAT functions as a polyspecific organic cation transporter and efficiently transports many organic cations such as monoamine neurotransmitters and 1-methyl-4-phenylpyridinium (MPP(+)). In this study, we explored the role of PMAT in the renal handling of organic cations. Using a polyclonal antibody generated toward the NH(2)-terminal 66 amino acid residues of human PMAT, we showed that the PMAT protein (approximately 55 kDa) is expressed in the human kidney and is primarily targeted to the apical membranes when expressed in polarized Madin-Darby canine kidney (MDCK) cells. Using MDCK cells stably expressing human PMAT, we showed that PMAT-mediated MPP(+) uptake is strongly dependent on extracellular pH. Lowering extracellular pH from 7.4 to 6.6 greatly stimulated PMAT-mediated MPP(+) uptake, whereas elevating extracellular pH to 8.2 abolished transporter activity. Kinetic analysis revealed that the apparent V(max) at pH 6.6 is about fourfold higher than that at pH 7.4, whereas the apparent K(m) values were not statistically different at these two conditions. Under acidic conditions (pH 6.6), the proton ionophore, carbonyl cyanide p-trifluormethoxyphenylhydrazone, drastically reduced PMAT-mediated MPP(+) uptake, suggesting that the stimulatory effect of proton may be due to transporter coupling with a proton gradient. Taken together, our data suggest that PMAT is expressed on the apical membranes of renal epithelial cells and may use luminal proton gradient to drive organic cation reabsorption in the kidney.