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The distribution of metronidazole susceptibility factors in clinically important bacteria was studied to determine why obligate anaerobes were susceptible to metronidazole and facultative ones were not. With obligate and facultative anaerobes, nitroreductase activity, metronidazole uptake, pyruvate:ferredoxin oxidoreductase activity and drug susceptibility were estimated. Nitroreductase activity was distributed in the obligate anaerobes and some facultative ones such as and most of the facultative anaerobes had no such activity. Bacteria with nitroreductase activity were able to absorb the drug. Pyruvate: ferredoxin oxidoreductase activity was distributed in all of the obligate anaerobes, whereas and all of the facultative anaerobes had no such activity. Distribution of metronidazole susceptibility was the same as that of pyruvate: ferredoxin oxidoreductase activity. Therefore metronidazole may selectively inhibit obligate anaerobes with pyruvate: ferredoxin oxidoreductase activity. Nitroreductase activity may be necessary for drug uptake as well. [ABSTRACT FROM PUBLISHER]

A combination of rabbit specific antiserum and amikacin showed a synergistic effect on the treatment of mice with lethal infections due to a strain of Klebsiella pneumoniae. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic highlighted the dangers of airborne transmission and the risks of pathogen-containing small airborne droplet inhalation as an infection route. As a pathogen control, Weakly Acidic Hypochlorous Water (WAHW) is used for surface disinfection. However, there are limited assessments of air disinfection by WAHW against airborne pathogens like bioaerosols. This was an empirical study evaluating the disinfection efficacy of WAHW in an atmospheric simulation chamber system against four selected model bacteria. The strains tested included Staphylococcus aureus (SA), Escherichia coli (EC), Pseudomonas aeruginosa (PA), and Pseudomonas aeruginosa (PAO1). Each bacterial solution was nebulized into the chamber system as the initial step, and bioaerosol was collected into the liquid medium by a bio-sampler for colony forming units (CFU) determination. Secondly, the nebulized bacterial bioaerosol was exposed to nebulized double distilled water (DDW) as the control and nebulized 150 ppm of WAHW as the experimental groups. After the 3 and 30-min reaction periods, the aerosol mixture inside the chamber was sampled in liquid media and then cultured on agar plates with different dilution factors to determine the CFU. Survival rates were calculated by a pre-exposed CFU value as a reference point. The use of WAHW decreased bacterial survival rates to 1.65-30.15% compared to the DDW control. PAO1 showed the highest survival rates and stability at 3 min was higher than 30 min in all experiments. Statistical analysis indicated that bacteria survival rates were significantly reduced compared to the controls. This work verifies the bactericidal effects against Gram-positive/negative bioaerosols of WAHW treatment. As WAHW contains chlorine in the acid solution, residual chlorine air concentration is a concern and the disinfection effect at different concentrations also requires investigation. Future studies should identify optimal times to minimize the treated time range and require measurements in a real environment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Retinoblastoma is a unilateral or bilateral intraocular tumor, occurring as a hereditary or sporadic tumor. Another not ocular lesion is a possibility for retinoblastoma carriers. The authors report the cases of two patients: a son with bilateral anophthalmic socket due to retinoblastoma, who presented unilateral upper eyelid tumor; and his father with unilateral anophthalmic socket secondary to enucleation due to retinoblastoma and a tumor growing fast in the upper eyelid at the same side of the anophthalmic cavity. Lesions were diagnosed as sebaceous carcinoma confirmed by immunohistochemical exam. Both patients had the eyelid tumors removed, with good resolution. None of them have presented either signs of recurrence or metastasis.

Purpose: To evaluate the profile of anophthalmic cavity carriers and patients' evolution with the employed treatments., Methods: Retrospective study carried out at Faculdade de Medicina de Botucatu, to evaluate the profile and the evolution of patients with anophthalmic cavity treated in our service. Data were evaluated according to the frequency of occurrence and analysis of association., Results: Anophthalmic cavity was more frequently observed in young males, workers in activities carried on with their hands. Trauma and phthisis bulbi were the most frequent causes, with differences according to age and gender. The complications were high (57.1% of cases), the majority occurred belatedly., Conclusions: Trauma is still an important cause of loss of the eye. The complications during the follow-up of the patient are frequent, occurring in general, very late, which reinforces the need for periodic and prolonged monitoring of patients with anophthalmic cavity.

Purpose: To observe the frequency of occurrence of eyelid basal cell carcinoma in the centralwest region of São Paulo State and to describe the demographic profile of the basal cell carcinoma carriers., Methods: Transversal study, using a random sampling, carried out in 12 cities in the centralwest region of São Paulo State evolving 11,167 individuals. Patients were evaluated in a Mobile Unit, with complete ophthalmologic evaluation. The diagnosis of eyelid basal cell carcinoma was done through clinical examination and biomicroscopy of the lesion if desirable. The basal cell carcinoma carriers diagnosed were referred to Oculoplastic Clinic of Faculdade de Medicina de Botucatu for treatment. Data were submitted to analysis of frequency of occurrence., Results: Five cases of eyelid basal cell carcinoma were identified in the sample, corresponding to a frequency of occurrence of 0.045%. Four patients were female, most with age equal or greater than 70 year-old and all the cases had white skin color. Only three individuals conveyed attended the service for excision of the lesion and diagnostic confirmation., Conclusion: The eyelid basal cell carcinoma affects 0.045% of the inhabitants of the centralwest region of São Paulo State, affecting mainly the 70 year-old female range.

1-(2-Methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1H-naphtho[2,3-d]imidazolium bromide (YM155 monobromide), which is a hydrophilic and cationic compound, exhibits antitumor activity in experimental human hormone refractory prostate carcinoma models. Urinary excretion was 18.3 to 28.6% of the dose in the clinical phase I study, and nonrenal elimination may be explained by the biliary excretion of YM155 in its unchanged form. Because the penetration through the sinusoidal membrane of the hepatocytes is the first step and an important part of biliary excretion, we evaluated the uptake of [(14)C]YM155 into human cryopreserved hepatocytes. YM155 was taken up into hepatocytes in a temperature- and concentration-dependent manner. The saturable uptake component was much higher than the nonsaturable passive diffusion component. In vitro hepatic uptake clearance was consistent with the in vivo hepatic intrinsic clearance calculated using clinical study data. Hepatic uptake of YM155 was inhibited by organic cation transporter (OCT) inhibitors, and the IC(50) values for YM155 uptake were comparable to those reported for human OCT1-mediated transport. The interaction of YM155 with candidate transporter, OCT1, was also characterized using S2 cells stably expressing human OCT1 (OCT1-S2) cells. In OCT1-expressing S2 cells, YM155 inhibited the OCT1-mediated uptake of a typical OCT1 substrate, [(14)C]tetraethylammonium. In addition, YM155 was taken up into OCT1-S2 cells These results indicated that OCT1 was the predominant transporter for the hepatic uptake of YM155, and the transporter-mediated uptake clearance observed in vitro may account for the in vivo intrinsic hepatic clearance.

Purpose: To present the characteristics of individuals and the prevalence of ectropium eyelid in a random sample of the state of São Paulo, Brazil., Methods: Data were collected during the Project on Prevention of Blindness, Faculty of Medicine of Botucatu - UNESP, a systematic random household sample was obtained. We evaluated 10,432 individuals, residents in 11 cities of the health regional located in the Central-Western region of the state of São Paulo. The results were submitted to statistical analysis to evaluate descriptive variables and the prevalence of ectropium eyelid., Results: Seventy-one ectropium eyelid patients were detected, with an estimated prevalence of 0.68%. The prevalence was not similar in all the studied municipalities. Most people with ectropium eyelid presented age over 70 years and were male. Cataract was concurrently present in 28.0% of them., Conclusion: The prevalence of ectropium population in the Central-Western region of São Paulo state is 0.68%. The ectropium eyelid affect mainly male, over 70 years relating sun light exposition and with normal visual acuity.

The aim of this study was to investigate the expression of p53, caspase-3, bcl-2, MIB-1, and PCNA to validate more objective methods to differentiate squamous cell carcinoma and keratoacanthoma, as well as to understand their pathogenesis with accuracy. A total of 52 cases of histopathologically diagnosed keratoacanthoma in the proliferative stage and 56 cases of well-differentiated squamous cell carcinoma were selected in this study. The expression was evaluated by means of immunohistochemistry. Bcl-2 immunoreactivity was weak or absent in the majority of cases, either in squamous cell carcinoma or in keratoacanthoma. PCNA-positive cells did not show differences between two lesions evaluated. On the other hand, MIB-1 was statistically significant (p<0.05) between squamous cell carcinomas and keratoacanthomas. Moreover, p53 and caspase-3 were overexpressed in squamous cell carcinomas. Together, these results suggest that the biological behavior of the well-differentiated squamous cell carcinomas of the skin may be associated with cellular proliferation and/or deregulation of cell death, indicated by increased expression of the MIB-1 and apoptotic proteins p53 and caspase-3, respectively.

Purpose: To investigate whether the channelopsin-2 (Chop2) gene would restore visual responses in 10-month-old dystrophic Royal College of Surgeons (aged RCS; rdy/rdy) rats, the authors transferred the Chop2 gene into the retinal cells of aged RCS rats using the adenoassociated virus (AAV) vector., Methods: The N-terminal fragment (residues 1-315) of Chop2 was fused to a fluorescent protein, Venus, in frame at the end of the Chop2 coding fragment. The viral vector construct (AAV-Chop2V) for the expression of the Chop2V in the retina was made by subcloning into an adenoassociated virus vector, including the CAG promoter. To evaluate the expression profile of Chop2V in the retina, the rats were killed and the eyes were removed and fixed with 4% paraformaldehyde in 0.1 M phosphate-buffered saline. Retinal wholemount specimens and cryosections were made. Under anesthetized conditions, electrodes for the recording of visually evoked potentials (VEPs) were implanted onto the visual cortex in aged-RCS (rdy/rdy) rats. AAV-Chop2V vectors were then injected into the vitreous cavity of the left eyes. As a control, AAV-Venus vectors were applied to the right eyes. VEPs were evoked by the flash of a blue, white, or red light-emitting diode (LED) and were recorded from the visual cortex of the rats at various time points after the AAV vector injection., Results: Chop2V fluorescence was predominantly observed in retinal ganglion cells (RGCs). Some fluorescence was observed in the inner nuclear layer and the inner plexiform layer neurites. A tendency of recovery was observed in the VEPs of aged RCS (rdy/rdy) rats after the AAV-Chop2V injection but not after the AAV-Venus injection. The visual response of AAV-Chop2V-injected aged RCS (rdy/rdy) rats was less sensitive to the blue LED flash than that of nondystrophic RCS (+/+) rats. The AAV-Chop2V-injected aged RCS (rdy/rdy) rats were insensitive to the red LED flash, which evoked a robust VEP in the RCS (+/+) rats., Conclusions: The visual response of aged RCS (rdy/rdy) rats was partially restored by transduction of the Chop2 gene through AAV into the inner retinal neurons, mainly RGCs. These results suggest that the transduction of Chop2 would provide a new strategy to treat some retinitis pigmentosa (RP) symptoms independent of their etiology.

Acute choice behavior in ingesting two different concentrations of sucrose in Drosophila is presumed to include learning and memory. Effects on this behavior were examined for four mutations that block associative learning (dunce, rutabaga, amnesiac, and radish). Three of these mutations cause cyclic AMP signaling defects and significantly reduced taste discrimination. The exception was radish, which affects neither. Electrophysiological recordings confirmed that the sensitivity of taste receptors is almost indistinguishable in all flies, whether wild type or mutant. These results suggest that food choice behavior in Drosophila involves central nervous learning and memory operating via cyclic AMP signaling pathways.

Purpose: To evaluate the eyelash alterations in anophthalmic cavity patients., Methods: An observational study was done looking for eyelash alterations in anophthalmic cavity patients at "Faculdade de Medicina de Botucatu"., Results: Eyelash alterations were observed in 70.7% of the anophthalmic patients. The most frequently observed eyelash alterations were eyelash ptosis (24.4%), reduction in the quantity (19.5%), trichomegaly (19.5%), trichiasis (14.6%) and entropium (17.0%)., Conclusion: The anophthalmic cavity patients have eyelash alteration and ptosis, reduction in quantity, trichomegaly, trichiasis are the most common observed situations. Further studies are needed to know more about it.

Objective: To compare cardiac structural changes in experimental pressure and volume overload models., Methods: The study analysis included renovascular hypertensive rats (RVH, n = 8), normotensive rats with volume overload caused by an aortocaval fistula (ACF, n = 10) and control rats (CONT, n = 8). After four weeks, tail cuff blood pressure (SBP) was recorded. Rats were killed, the hearts were excised and the right and left ventricles (RV&LV) were weighed (RVW&LVW). Using histological sections, myocyte cross sectional areas (MA). LV wall thickness (LVWT) LV cavity diameter (LVD), normalized LVWT (LVWT/LVD) and collagen volume fraction (CVF) were measured. The comparisons were made using the ANOVA and Tukey test for a significance level of 5%., Results: Tail cuff blood pressure (mmHg) was higher in the RVH group (RVH = 187 +/- 22; CONT = 125 +/- 10; ACF = 122 +/- 6, p < 0.05). LV hypertrophy was observed in the RVH and ACF groups. The ACF group presented a significant increase in size of LVD, compared to CONT and RVH. The absolute and normalized ventricular wall thickness were similar among the groups. The RVH group presented a significant increase in CVF compared to CONT group and ACF group., Conclusion: Cardiac remodeling patterns following volume or pressure overload are distinct, suggesting that their implications on ventricular dysfunction are not interchangeable.

Purpose: To determine the success rate of probing for congenital nasolacrimal duct obstruction and the factors related to probe failure., Method: A retrospective observational study was conducted, involving 80 children with congenital nasolacrimal obstruction who underwent nasolacrimal probing. The subjects were evaluated according to sex, age and probing outcome. The data were evaluated according to the descriptive method, Goodman test and Mann-Whitney test adopting a significance of 5%., Results: The possibility of cure was the same in both sexes. The mean age at cure was 19.95+/-11.44 months and on failure was 23.67+/-15.21 months. The analysis showed no significant change in cure rate when over 6 months old. Nasal alterations such as rhinitis, mucosal or turbinate bone hypertrophy, septum deviation and sinusitis were associated with probe failure., Conclusion: The cure rate does not vary significantly at intervals of increasing ages even it over 12 months old. Nasal alterations might be included in the causes of failure.

Zonampanel monohydrate (YM872; [2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]acetic acid monohydrate) is a novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist. The major elimination route for zonampanel has been reported to be by urine via the kidneys. The purpose of this study is to elucidate the molecular mechanism of the renal excretion of zonampanel using cells stably expressing human organic anion transporters (hOAT) 1, hOAT2, hOAT3, and hOAT4, as well as human organic cation transporters (hOCT) 1 and hOCT2. Another AMPA receptor antagonist, YM90K [6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione monohydrochloride], a decarboxymethylated form of zonampanel, was also used for comparing the substrate specificity. Zonampanel inhibited the uptake of prototypical organic anion substrates, [14C]para-aminohippurate in hOAT1 and [3H]estrone sulfate in hOAT3 and hOAT4, in a competitive manner. A time- and concentration-dependent increase in [14C]zonampanel uptake was observed in cells expressing hOAT1, hOAT3, and hOAT4. The Km values of zonampanel uptake by hOAT1, hOAT3, and hOAT4 were 1.4, 7.7, and 215 microM, respectively. Considering the localization of each transporter, results suggest that zonampanel is taken up via hOAT1 and hOAT3 from the blood into proximal tubular cells and then effluxed into the lumen via hOAT4. Probenecid and cimetidine competitively inhibited [14C]zonampanel uptake by the hOATs (hOAT1, hOAT3, and hOAT4 for probenecid; hOAT3 for cimetidine). YM90K inhibited the uptake of the prototypical substrate via hOAT3 competitively, but the uptake via hOAT1 noncompetitively. These findings suggest that the prototypical organic anion substrates (para-aminohippurate and estrone sulfate), cimetidine, probenecid, and zonampanel share binding specificity in each hOAT, whereas YM90K does not in hOAT1, possibly due to it being the decarboxymethylated form.

Antiarrhythmic drugs have been considered to be transported by the organic cation transport system. The purpose of this study was to elucidate the molecular mechanism underlying the transport of antiarrhythmic drugs using cells from the second segment of the proximal tubule (S2) cells of mice expressing human-organic cation transporter 3 (S2 human-OCT3). The antiarrhythmic drugs tested were cibenzoline, disopyramide, lidocaine, mexiletine, phenytoin, pilsicanide, procainamide and quinidine. Human-OCT3 mediated a time- and dose-dependent uptake of quinidine and lidocaine, with Km values of 216 and 139 microM, respectively. Human-OCT3 also mediated the uptake of disopyramide and procainamide but not that of phenytoin. All antiarrhythmic drugs tested inhibited histamine uptake mediated by human-OCT3 in a dose-dependent manner. The IC50 values of antiarrhythmic drugs for human-OCT3 ranged between 0.75 and 656 microM. Kinetic analysis revealed that disopyramide, lidocaine, procainamide and quinidine inhibited histamine uptake mediated by human-OCT3 in a competitive manner. In conclusion, these results suggest that human-OCT3 mediates the transport of antiarrhythmic drugs, which may be the mechanism underlying the distribution and the elimination of these drugs.

The tubular secretion of diuretics in the proximal tubule has been shown to be critical for the action of drugs. To elucidate the molecular mechanisms for the tubular excretion of diuretics, we have elucidated the interactions of human organic anion transporters (hOATs) with diuretics using cells stably expressing hOATs. Diuretics tested were thiazides, including chlorothiazide, cyclothiazide, hydrochlorothiazide, and trichlormethiazide; loop diuretics, including bumetanide, ethacrynic acid, and furosemide; and carbonic anhydrase inhibitors, including acetazolamide and methazolamide. These diuretics inhibited organic anion uptake mediated by hOAT1, hOAT2, hOAT3, and hOAT4 in a competitive manner. hOAT1 exhibited the highest affinity interactions for thiazides, whereas hOAT3 did those for loop diuretics. hOAT1, hOAT3, and hOAT4 but not hOAT2, mediated the uptake of bumetanide. hOAT3 and hOAT4, but not hOAT1 mediated the efflux of bumetanide. hOAT1 and hOAT3, but not hOAT2 and hOAT4 mediated the uptake of furosemide. In conclusion, it was suggested that hOAT1 may play an important role in the basolateral uptake of thiazides, and hOAT3 in the uptake of loop diuretics. In addition, it was also suggested that bumetanide taken up by hOAT3 and/or hOAT1 is excreted into the urine by hOAT4.

We have elucidated the interactions of human and rat organic anion transporters (hOATs and rOATs) with pravastatin and cimetidine. Pravastatin inhibited hOAT1/rOAT1, hOAT2/rOAT2, hOAT3/rOAT3, and hOAT4. The mode of inhibition was noncompetitive for hOAT1 and hOAT2, whereas it was competitive for hOAT3 and hOAT4. Cimetidine also inhibited hOAT1/rOAT1, hOAT3/rOAT3, and hOAT4. The mode of inhibition was a combination of competitive and noncompetitive manners for hOAT1, whereas it was competitive for hOAT3. The effects of OAT inhibitors on OAT1, OAT2, and OAT3 exhibited some but not so remarkable interspecies differences between humans and rats. In conclusion, we have characterized pravastatin and cimetidine as OAT inhibitors.

The purpose of this study was to elucidate the role of human organic anion transporters (human OATs) in the induction of drug-induced skeletal muscle abnormalities. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have been clinically used for lowering plasma cholesterol levels, and are known to induce various forms of skeletal muscle abnormalities including myopathy and rhabdomyolysis. Immunohistochemical analysis revealed that human OAT1 and human OAT3 are localized in the cytoplasmic membrane of the human skeletal muscles. The activities of human OATs were measured using mouse cell lines from renal proximal tubules stably expressing human OATs. Human OAT3, but not human OAT1, mediates the transport of pravastatin. Fluvastatin inhibited organic anion uptake mediated by human OAT1 in a mixture of competitive and noncompetitive manner, whereas simvastatin and fluvastatin noncompetitively inhibited the organic anion uptake mediated by human OAT3. In conclusion, the organic anion transporters OAT1 and OAT3 are localized in the cytoplasmic membrane of human skeletal muscles. Pravastatin, simvasatin, and fluvasatin inhibit human OATs activity. These results suggest that muscle organic anion transporters play a role in the muscular side effects of HMG-CoA reductase inhibitors.

The purpose of the present study was to elucidate the expression of human organic anion transporter 1 (hOAT1) and hOAT3 in the choroid plexus of the human brain and their interactions with neurotransmitter metabolites using stable cell lines. Immunohistochemical analysis revealed that hOAT1 and hOAT3 are expressed in the cytoplasmic membrane and cytoplasm of human choroid plexus. Neurotransmitter metabolites, namely, 5-methoxyindole-3-acetic acid (5-MI-3-AA), homovanillic acid (HVA), vanilmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindole-3-acetic acid (5-HI-3-AA), N-acetyl-5-hydroxytryptamine (NA-5-HTT), melatonin, 5-methoxytryptamine (5-MTT), 3,4-dihidroxymandelic acid (DHMA), 5-hydroxytryptophol, and 5-methoxytryptophol (5-MTP), but not methanephrine (MN), normethanephrine (NMN), and 3-methyltyramine (3-MT), at 2 mM, inhibited para-aminohippuric acid uptake mediated by hOAT1. On the other hand, melatonin, 5-MI-3-AA, NA-5-HTT, 5-MTT, 5-MTP, HVA, 5-HI-3-AA, VMA, DOPAC, 5-hydroxytryptophol, and MN, but not 3-MT, DHMA, and NMN, at 2 mM, inhibited estrone sulfate uptake mediated by hOAT3. Differences in the IC(50) values between hOAT1 and hOAT3 were observed for DHMA, DOPAC, HVA, 5-HI-3-AA, melatonin, 5-MI-3-AA, 5-MTP, 5-MTT, and VMA. HOAT1 and hOAT3 mediated the transport of VMA but not HVA and melatonin. These results suggest that hOAT1 and hOAT3 are involved in the efflux of various neurotransmitter metabolites from the cerebrospinal fluid to the blood across the choroid plexus.

Cephalosporin antibiotics are thought to be excreted into the urine via organic anion transporters (OATs) and OAT can mediate nephrotoxicity by cephalosporins, particularly by cephaloridine. The purpose of this study was to elucidate the interaction of human-OAT2 and rat-OAT2 with cephalosporin antibiotics using proximal tubule cells stably expressing human-OAT2 and rat-OAT2. Human-OAT2 is localized to the basolateral side of the proximal tubule, whereas rat-OAT2 is localized to the apical side of the proximal tubule. Cephalosporins tested were cephalothin, cefoperazone, cefazolin, ceftriaxone, cephaloridine, cefotaxime, cefadroxil and cefamandole. These cephalosporins dose-dependently inhibited organic anion uptake mediated by human-OAT2 and rat-OAT2. There was no species difference observed for the effects of OAT2 with cephalosporins between human and rat transporters. Kinetic analysis revealed that the inhibitory effects for human-OAT2 were competitive. Cephaloridine significantly decreased the viability of cells stably expressing human-OAT2, human-OAT1, human-OAT3 and human-OAT4. The decreased viability of cells stably expressing human-OAT1, human-OAT3 and human-OAT4 but not human-OAT2 was reversed by probenecid. In conclusion, human-OAT2 interacts with cephalosporins, and thus, human-OAT2 may mediate the uptake of cephalosporins on the basolateral side of the proximal tubule. The interaction of human-OAT2 with cephalosporins was the weakest among the basolateral human-OATs tested. In addition, it is suggested that human-OATs mediate cephaloridine-induced nephrotoxicity.

The purpose of this study was to elucidate the interactions of human organic anion transporters (hOATs) and human organic cation transporters (hOCTs) with nonsteroidal anti-inflammatory drugs (NSAIDs) using cells stably expressing hOATs and hOCTs. NSAIDs tested were acetaminophen, acetylsalicylate, salicylate, diclofenac, ibuprofen, indomethacin, ketoprofen, mefenamic acid, naproxen, piroxicam, phenacetin, and sulindac. These NSAIDs inhibited organic anion uptake mediated by hOAT1, hOAT2, hOAT3, and hOAT4. By comparing the IC(50) values of NSAIDs for hOATs, it was found that hOAT1 and hOAT3 exhibited higher affinity interactions with NSAIDs than did hOAT2 and hOAT4. HOAT1, hOAT2, hOAT3, and hOAT4 mediated the uptake of either ibuprofen, indomethacin, ketoprofen, or salicylate, but not acetylsalicylate. Although organic cation uptake mediated by hOCT1 and hOCT2 was also inhibited by some NSAIDs, hOCT1 and hOCT2 did not mediate the uptake of NSAIDs. In conclusion, hOATs and hOCTs interacted with various NSAIDs, whereas hOATs but not hOCTs mediated the transport of some of these NSAIDs. Considering the localization of hOATs, it was suggested that the interactions of hOATs with NSAIDs are associated with the pharmacokinetics and the induction of adverse reactions of NSAIDs.