Burckhardt. Transport of cimetidine by flounder and human renal organic anion transporter 1. Am J Physiol Renal Physiol 284: F503-F509, 2003. First published November 12, 2002 10.1152/ajprenal.00290.2002The H 2-receptor antagonist cimetidine is efficiently excreted by the kidneys. In vivo studies indicated an interaction of cimetidine not only with transporters for basolateral uptake of organic cations but also with those involved in excretion of organic anions. We therefore tested cimetidine as a possible substrate of the organic anion transporters cloned from winter flounder (fROAT) and from human kidney (hOAT1). Uptake of [ 3 H]cimetidine into fROAT-expressing Xenopus laevis oocytes exceeded uptake into control oocytes. At Ϫ60-mV clamp potential, 1 mM cimetidine induced an inward current, which was smaller than that elicited by 0.1 mM PAH. Cimetidine concentrations exceeding 0.1 mM decreased PAH-induced inward currents, indicating interaction with the same transporter. At pH 6.6, no current was seen with 0.1 mM cimetidine, whereas at pH 8.6 a current was readily detectable, suggesting preferential translocation of uncharged cimetidine by fROAT. Oocytes expressing hOAT1 also showed [ 3 H]cimetidine uptake. These data reveal cimetidine as a substrate for fROAT/hOAT1 and suggest that organic anion transporters contribute to cimetidine excretion in proximal tubules.winter flounder renal organic anion transporter; organic anion transport; organic cation transport; kidney AS A SPECIFIC ANTAGONIST OF histamine H 2 receptors, cimetidine acts on gastric parietal cells to inhibit HCl secretion stimulated by histamine, pentagastrin, and acetylcholine. Between 50 and 80% of the dose administered intravenously was recovered in urine as unchanged cimetidine, and elimination half-life was ϳ2 h in healthy volunteers with normal kidney and hepatic function (24). The mean steady-state plasma concentration on a standard 1,000-mg daily dose was 1 g/ml (range 0.64-1.64 g/ml). A renal clearance of 600 ml/ min (24), exceeding the glomerular filtration rate by approximately fivefold, indicated an efficient tubular secretion of cimetidine. Therefore, cimetidine must interact with renal transporters, most probably with those located in the proximal tubules.Because at physiological pH part of the cimetidine is positively charged, the organic cation transport systems of the proximal tubule cell are expected to be involved in cimetidine secretion. The two-step model of transcellular organic cation secretion consists of electrogenic uptake at the basolateral side, moving organic cations down their electrochemical gradient from blood into proximal tubular cells, and organic cation/proton exchange mediating uphill exit into the lumen. The cloned organic cation transporters, OCT1, OCT2, and OCT3, are electrogenic and likely contribute to organic cation uptake across the basolateral membrane (for reviews, see Refs. 6 and 18). In accordance with their function, rat OCT1 and OCT2 were localized to the basolateral membrane of proximal tubule ce...

Human airways are continuously colonized by microaspiration of microbiota. Less is known about the presence, origin and composition of microbiota in the lung parenchyma. In a study of 13 patients undergoing surgery for peripheral lung cancer microbiota composition was comparatively evaluated in upper airway, lower airway and lung tissue samples using 16S rDNA analysis. Bacterial density decreased stepwise from upper to lower airways and tissue. On a taxonomic level upper and lower airway microbiota were similar whereas lung tissue showed marked dissimilarities compared to lower airways that may reflect different environmental conditions shaping local microbiota and host immunity.

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Background Coronavirus disease 2019 (COVID-19) is an infection which can affect the central nervous system. In this study, we sought to investigate associations between neuroimaging findings with clinical, demographic, blood and cerebrospinal fluid (CSF) parameters, pre-existing conditions and the severity of acute COVID-19. Materials and methods Retrospective multicenter data retrieval from 10 university medical centers in Germany, Switzerland and Austria between February 2020 and September 2021. We included patients with COVID-19, acute neurological symptoms and cranial imaging. We collected demographics, neurological symptoms, COVID-19 severity, results of cranial imaging, blood and CSF parameters during the hospital stay. Results 442 patients could be included. COVID-19 severity was mild in 124 (28.1%) patients (moderate n = 134/30.3%, severe n = 43/9.7%, critical n = 141/31.9%). 220 patients (49.8%) presented with respiratory symptoms, 167 (37.8%) presented with neurological symptoms first. Acute ischemic stroke (AIS) was detected in 70 (15.8%), intracranial hemorrhage (IH) in 48 (10.9%) patients. Typical risk factors were associated with AIS; extracorporeal membrane oxygenation therapy and invasive ventilation with IH. No association was found between the severity of COVID-19 or blood/CSF parameters and the occurrence of AIS or IH. Discussion AIS was the most common finding on cranial imaging. IH was more prevalent than expected but a less common finding than AIS. Patients with IH had a distinct clinical profile compared to patients with AIS. There was no association between AIS or IH and the severity of COVID-19. A considerable proportion of patients presented with neurological symptoms first. Laboratory parameters have limited value as a screening tool.