[An analysis of the outbreak situation and background risk factors for drug-resistant urinary tract infection in nursing homes].

AIM: The present study clarified the outbreak situation and background risk factors for drug-resistant bacteria infection in nursing homes. METHODS: Subjects were 48 elderly individuals with urinary tract infections in 3 nursing homes during the 12-month period from January to December 2020. We analyzed the drug resistance of cultured bacteria using medical records. RESULTS: Escherichia coli was the most frequently cultured bacteria (37.1%), and extended-spectrum ß-lactamase (ESBL) -producing E. coli accounted for 26.1% of specimens. E. coli susceptibility to levofloxacin (LVFX) was seen in 47.8%, resistance in 47.8%, and intermediate response in 4.4%. E. coli susceptibility to ceftriaxone (CTRX) was seen in 73.9%, and resistance in 26.1%. E. coli susceptibility to sulfamethoxazole trimethoprim (ST) mixture was seen 81.8%, while resistance was seen in 18.2%. In addition, among ESBL-producing E. coli, susceptibility to LVFX was seen in 0% and resistance in 83.3%, and an intermediate response was seen in 16.7%, while susceptibility to ST mixture was seen in 83.3% and resistance in 16.7%. No marked differences in background risk factors were seen between the groups with LVFX-resistant and LVFX-susceptible E. coli. However, the body mass index was significantly lower (p=0.0389), and significantly more patients were treated with antimicrobial agents during the 1-year period preceding the sample acquisition and analysis (p=0.0418) in the group with CTRX-resistant E. coli than in the group with CTRX-susceptible E. coli. CONCLUSION: In the nursing homes examined, LVFX-resistant E. coli were highly prevalent, and ESBL-producing bacteria were also common. When we treat urinary tract infections, refraining from the use of LVFX is desirable, and antimicrobials should be chosen with care.

Modification of cardiac disease by transgenically altered histone deacetylase 6.

Histone deacetylase 6 (HDAC6) is known to deacetylate amino acid lysine in alpha-tubulin. However, the functional role of HDAC6 in the progression of cardiac disease remains uncertain. The functional role of HDAC6 in the hearts was examined using transgenic (TG) mice expressing either human wild-type HDAC6, deacetylase inactive HDAC6 (HDAC6H216A, H611A), and human HDAC6 replaced all serine or threonine residues with aspartic acid at N-terminal 1- 43 amino acids (HDAC6NT-allD) specifically in the hearts. Overexpression of wild-type HDAC6 significantly reduced acetylated tubulin levels, and overexpression of HDAC6H216A, H611A significantly increased it in the mouse hearts. Detectable acetylated tubulin disappeared in HDAC6NT-allD TG mouse hearts. Neither histological alteration nor alteration of cardiac function was observed in the HDAC6 TG mouse hearts. To analyze the role of HDAC6 and acetylated tubulin in disease conditions, we examined HDAC6 in isoprenaline-induced hypertrophy or pressure-overload hypertrophy (TAC). No obvious alteration in the heart weight/body weight ratio or gene expressions of hypertrophic markers between NTG and HDAC6NT-allD mice was observed following treatment with isoprenaline. In contrast, a marked reduction in the shortening fraction and dilated chamber dilatation was detected in the HDAC6NT-allD TG mouse hearts 2 weeks after TAC. A sustained low level of acetylated tubulin and acetylated cortactin was observed in the TAC HDAC6NT-allD TG mouse hearts. Cardiac HDAC6 activity that can regulate acetylated levels of tubulin and cortactin may be critical factors involved in cardiac disease such as pressure-overload hypertrophy.

Free formaldehyde in non-medical face masks purchased from the Japanese market since the COVID-19 outbreak.

Since the Coronavirus Disease 2019 (COVID-19) pandemic began, people have been wearing face masks for many hours every day. As these face masks are in contact with the skin, it is important to pay more attention to their quality and safety. This study examined the concentration of free formaldehyde in 90 non-medical face masks and related products (33 nonwoven, 30 woven cloth, 12 polyurethane, and 15 related products) because formaldehyde is a common contact allergen in textile products. For products consisting of mixed materials, each material was sampled, resulting in 103 samples for analysis. Free formaldehyde (34-239 µg/g) was found in three cloth masks, which consisted of cotton and polyester, with antibacterial and antiviral labeling. It was confirmed that the detected formaldehyde originated from the mask-finishing treatment by a hydrochloric acid extraction discrimination test. These masks may elicit contact dermatitis if the consumers have already been sensitized to formaldehyde. However, the risk of contact dermatitis caused by formaldehyde in masks may be considered low since the frequency of formaldehyde detection in masks in Japan is low.

A Case of Concurrent Extramammary Paget Disease and Basal Cell Carcinoma of the Perianal Region.

An 83-year-old Japanese man who had been aware of a tumor near his anus for 2 years underwent tumor resection. Although he was diagnosed with basal cell carcinoma (BCC), extramammary Paget disease (EMPD) was also accidentally found in the same specimen. In the pathological histology of EMPD, there were large round cells with ample cytoplasm spread in the epidermis; these cells were positive for cytokeratin 7 and gross cystic disease fluid protein 15. No signs that are typically associated with EMPD, such as erythema or leukoderma, were observed near the anus. There have been only 4 reports in which BCC and EMPD developed in the same area, and the authors present the fifth case. In the reported case, no clear evidence was found for the corelative development of BCC and EMPD.

Reishi mushroom Ganoderma lucidum Modulates IgA production and alpha-defensin expression in the rat small intestine.

ETHNOPHARMACOLOGICAL RELEVANCE: Immunoglobulin A (IgA) secretion and alpha-defensins play a role in the innate immune system to protect against infection. Ganoderma lucidum (W.Curt.: Fr.) P. Karst. (Reishi) is a well-known mushroom in traditional Chinese medicine. This study aimed to determine the effects of Reishi on IgA secretion from Peyer's patch (PP) cells and alpha-defensin-5 (RD-5) and RD-6 expression in the rat small intestine. MATERIALS AND METHODS: The rats received an oral injection of 0.5-5mg/kg of Reishi powder (1mL/kg) by sonde. All animals were euthanized 24h after Reishi administration. We examined RD-5, RD-6, and Toll-like receptor (TLR) 4 mRNA levels in the jejunum, ileum, and in Peyer's patches (PP) through quantitative real-time PCR analysis. IgA secretion from PP was measured through enzyme-linked immunosorbent assay of the supernatant after primary culture. RESULTS: Reishi increased IgA secretion in the presence of lipopolysaccharide (LPS) and increased TLR4 mRNA levels, but had no effect on the viability of PP cells. Moreover, Reishi increased RD-5, RD-6, and TLR4 mRNA levels significantly in the ileum in a concentration-dependent manner. CONCLUSIONS: Reishi can induce IgA secretion and increase the mRNA levels of RD-5 and RD-6 in the rat small intestine, through a TLR4-dependent pathway. The present results indicate that Reishi might reduce the risk of intestinal infection.

Insulin stimulates transport of organic anion compounds mediated by organic anion transporting polypeptide 2B1 in the human intestinal cell line Caco-2.

Organic anion transporting polypeptide 2B1 (OATP2B1) is the major uptake transporter in the intestine, and transports various clinically used therapeutic agents. Insulin acts through the insulin receptor in targeted cells, and Rab8A is one of the insulin signaling pathways. The small intestine in humans also expresses insulin receptor and Rab8A. It has been reported that insulin stimulates peptide transporter 1 (PEPT1) expression at the apical membrane and increases uptake of PEPT1 substrates in small intestine epithelial model cells (Caco-2 cells). However, the effect of insulin on OATP2B1 in the small intestine has not been fully investigated. We found that Rab8A was associated with OATP2B1-mediated estrone-3-sulfate (E3S) uptake. Insulin stimulated the uptake of E3S by Caco-2 cells and the enhancement was sustained for 120 min. The Vmax value of E3S uptake significantly increased upon insulin exposure. Caco-2 cells treated with insulin showed increased OATP2B1 expression at the cell surface. The apical-to-basal transport of E3S was also increased by insulin. The increase of E3S transport was inhibited by the cold condition (4 °C) or the OATP2B1 inhibitor, taurocholate. These results indicate that insulin acts on the small intestine to increase OATP2B1-mediated absorption.

Inhibitory Effects of Eight Green Tea Catechins on Cytochrome P450 1A2, 2C9, 2D6, and 3A4 Activities.

PURPOSE: Green tea is a traditional beverage that has been enjoyed by the Japanese to this day. Recently, there has been an increase in the consumption of green tea beverage having high concentrations of catechins, such as (-)-epigallocatechin-3-O-gallate (EGCG). Many people tend to ingest large amounts of catechins through the frequent consumption of green tea beverage, and this dietary habit may lead to unwanted interactions between the catechins in green tea and medicinal drug. METHODS: The inhibitory effects of eight green tea catechins on drug metabolizing enzymes, cytochrome P450 (CYP) 1A2, 2C9, 2D6, and 3A4, were investigated in human liver microsomes. Incubation was initiated by the addition of cocktail probe drugs that served as specific substrates for each CYP, and the resulting metabolites were analyzed by LC-MS. RESULTS: From a comparison of the fifty percent inhibitory concentration (IC50) values of the eight green tea catechins, it was found that non-gallated catechins did not inhibit CYPs, whereas gallated catechins inhibited all CYPs except CYP2D6. Among them, CYP2C9 was most strongly inhibited by (-)-catechin-3-O-gallate (CG) (7.60 µM), and CYP1A2 was most strongly inhibited by EGCG (8.93 µM). Catechin gallate exhibited non-competitive inhibition of CYP2C9, and its Ki value was 9.76 ± 0.47µM. The present study is the first to report the inhibitory effect of CG on CYP2C9. In contrast, EGCG showed competitive inhibition of CYP1A2, and its Ki value was 14.3 ± 0.09 µM. CONCLUSION: Previous reports had predicted that plasma EGCG concentration reached 7.4 µM after ingesting green tea having high concentrations of catechins. That concentration of EGCG is equivalent to one-half to one-third of its Ki value for CYP1A2 and CYP3A4 in this study. The ingestion of beverages containing large amounts of green tea catechins together with drugs that are metabolized by CYP1A2, CYP2C9, and CYP3A4 should be avoided. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Characterization of loxoprofen transport in Caco-2 cells: the involvement of a proton-dependent transport system in the intestinal transport of loxoprofen.

Loxoprofen, a propionate non-steroidal anti-inflammatory drug (NSAID), is used widely in East Asian countries. However, little is known about the transport mechanisms contributing to its intestinal absorption. The objectives of this study were to characterize the intestinal transport of loxoprofen using the human intestinal Caco-2 cell model. The transport of loxoprofen was investigated in cellular uptake studies. The uptake of loxoprofen into Caco-2 cells was pH- and concentration-dependent, and was described by a Michaelis-Menten equation with passive diffusion (Km : 4.8 mm, Vmax : 142 nmol/mg protein/30 s, and Kd : 2.2 µl/mg protein/30 s). Moreover, the uptake of loxoprofen was inhibited by a typical monocarboxylate transporter (MCT) inhibitor as well as by various monocarboxylates. The uptake of [14 C] l-lactic acid, a typical MCT substrate, in Caco-2 cells was saturable with relatively high affinity for MCT. Because loxoprofen inhibited the uptake of [14 C] l-lactic acid in a noncompetitive manner, it was unlikely that loxoprofen uptake was mediated by high-affinity MCT(s). Our results suggest that transport of loxoprofen in Caco-2 cells is, at least in part, mediated by a proton-dependent transport system. Copyright © 2016 John Wiley & Sons, Ltd.

Causes of macrocytic anemia among 628 patients: mean corpuscular volumes of 114 and 130 fL as critical markers for categorization.

There have been no studies on the distribution of causes of macrocytic anemia with respect to mean corpuscular volume (MCV) cutoff values. We retrospectively investigated the causes of macrocytic anemia (MCV ≥100 fL) among 628 patients who visited the outpatient hematology clinic in Tohoku University Hospital. To ensure data validity, we also analyzed data from 307 patients in eight other hospitals in the Tohoku district. The leading causes of macrocytic anemia (number of patients, %) were myelodysplastic syndromes (121, 19.3 %), suspected bone marrow failure syndromes (BMF; 74, 11.8 %), aplastic anemia (51, 8.1 %), plasma cell dyscrasia (45, 7.2 %), and vitamin B12 deficiency (40, 6.4 %) in Tohoku University Hospital. We made three primary findings as follows. First, the most common cause of macrocytic anemia is BMF. Second, lymphoid and solid malignancies are also common causes of macrocytosis. Third, macrocytic anemia may be classified into three groups: Group 1 (megaloblastic anemia and medications), which can exceed MCV 130 fL; Group 2 (alcoholism/liver disease, BMF, myeloid malignancy, and hemolytic anemia), which can exceed MCV 114 fL; and Group 3 (lymphoid malignancy, chronic renal failure, hypothyroidism, and solid tumors), which does not exceed MCV 114 fL. These conclusions were supported by the results from eight other hospitals.

Involvement of Monocarboxylate Transporter 4 Expression in Statin-Induced Cytotoxicity.

Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are the most widely used cholesterol-lowering agents for prevention of obstructive cardiovascular events. However, statins can cause a variety of skeletal muscle problems, and exercise leads to an increase in statin-induced muscle injury. Exercise induces the protein content of monocarboxylate transporter 4 (MCT4), which is expressed strongly in skeletal muscle and is thought to play a major role in the transport of metabolically important monocarboxylates such as l-lactate. We previously reported that α-cyano-4-hydroxycinnamate, an MCT4 inhibitor, increased the inhibition of growth of RD cells, a prototypic embryonal rhabdomyosarcoma cell line (an RD cell line), as a model of in vitro skeletal muscle, induced by a statin. However, it is unclear whether statin-induced RD cell cytotoxicity is associated with MCT4 expression. We, therefore, examined the relationship between statin-induced cytotoxicity and MCT4 expression in RD cells. Atorvastatin reduced the number of viable cells and upregulated MCT4, but not MCT1, mRNA level in a concentration-dependent manner. MCT4 knockdown suppressed atorvastatin-, simvastatin-, and fluvastatin-induced reduction of cell viability and apoptosis compared with negative control-treated cells. In this study, we demonstrated that MCT4 expression is associated with statin-induced cytotoxicity.

Three-dimensional ultrasonography for visualization of muscular anomalies in type VI and VII radial polydactyly.

OBJECTIVE: To describe a technique and its clinical applications of three-dimensional ultrasonography to type VI and VII radial polydactyly for identification of potential muscular anomalies. MATERIALS AND METHODS: Ultrasonographic examinations were performed at an out-patient department without sedation or an operative room prior to surgery. The palm was scanned in the transverse direction using a 18-MHz linear transducer under speed regulation at 3 mm/s. Sequential images acquired at 0.2 mm intervals were converted into volume data. After validation of the technique, patients with a radial polydactyly in association with triphalangism (type VII) or with polydactylies of metacarpal duplication (type VI) were included for the examination. RESULTS: Five hands of five patients, one with type VI and four with type VII, were included the study. All the patients were male and the ages at examination ranged from 7 months to 2 years. Of the five patients, four examinations were performed at an out-patient department without sedation and one was under anesthesia just prior to surgery. The muscular abnormalities identified were mal-positions of the thenar muscles in a type VI case and a deficiency of the abductor pollicis brevis muscle in a type VII case with a delta phalanx in the ulnar part. CONCLUSION: Three-dimensional ultrasound technique could be an aid to plan strategies in radial polydactyly if intrinsic muscular anomalies are suspected to be involved.

Inhibitory effect of black tea and its combination with acarbose on small intestinal α-glucosidase activity.

ETHNOPHARMACOLOGICAL RELEVANCE: It is said that black tea is effective against type 2 diabetes mellitus because it can help modulate postprandial hyperglycemia. However, the mechanism underlying its therapeutic and preventive effects on type 2 diabetes mellitus is unclear. In this study, we focused on the effect of black tea on the carbohydrate digestion and absorption process in the gastrointestinal tract. We examined whether black tea can modulate postprandial hyperglycemia. MATERIALS AND METHODS: The freeze-dried powder of the aqueous extract of black tea leaves (JAT) was used for in vitro studies of α-amylase activity, α-glucosidase activity, and glucose uptake by glucose transporters in Caco-2 cells; ex vivo studies of small intestinal α-glucosidase activity; and in vivo studies of oral sugar tolerance in GK rats, an animal model of nonobese type 2 diabetes mellitus. RESULTS: Half maximal inhibitory concentration values indicated that JAT significantly reduced α-glucosidase activity, but weakly reduced α-amylase activity. Kinetic studies of rat small intestinal α-glucosidase activity revealed that the combination of JAT and the α-glucosidase inhibitor, acarbose, showed a mixed-type inhibition. JAT had no effect on the uptake of 2'-deoxy-d-glucose by glucose transporter 2 (GLUT2) and the uptake of α-methyl-d-glucose by sodium-dependent glucose transporter 1 (SGLT1). In the oral sucrose tolerance test in GK rats, JAT reduced plasma glucose levels in a dose-dependent manner compared with the control group. The hypoglycemic action of JAT was also confirmed: JAT, in combination with acarbose, produced a synergistic inhibitory effect on plasma glucose levels in vivo. In contrast to the oral sucrose tolerance test, JAT showed no effect in the oral glucose tolerance test. CONCLUSIONS: JAT was demonstrated to inhibit the degradation of disaccharides into monosaccharides by α-glucosidase in the small intestine. Thereby indirectly preventing the absorption of the dietary source of glucose mediated by SGLT1 and GLUT2 transporters localized at the apical side of enterocytes in the small intestine. The results indicate that black tea could be useful as a functional food in the dietary therapy for borderline type 2 diabetes mellitus that could modulate postprandial hyperglycemia.

Alteration of pharmacokinetics of grepafloxacin in type 2 diabetic rats.

PURPOSE: Patients with type 2 diabetes are generally treated with various pharmacological compounds and are exposed to a high risk of drug-drug interactions. However, alterations of pharmacokinetics in a type 2 diabetes model have been obscure. The present study was undertaken to investigate the effects of type 2 diabetes on the pharmacokinetics of the fluoroquinolone grepafloxacin (GPFX) and the expression level of P-glycoprotein (P-gp), one of the drug efflux transporters. METHODS: We used Goto-Kakizaki (GK) rats, a lean model of type 2 diabetes. Plasma concentration and intestinal, renal, and biliary clearance of GPFX were measured after intravenous and intraintestinal administration in Wistar and GK rats. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. RESULTS: We found a significant increase in the plasma concentrations of GPFX at 90, 120 and 240 minutes after intraintestinal administration in GK rats compared with the concentrations in Wistar rats but not after intravenous administration. The increase in plasma GPFX concentration was associated with reduction in jejunal clearance of GPFX caused by a decrease in secretory transport of GPFX. However, there was no correlation between the decrease in secretory transport of GPFX and P-gp expression level. CONCLUSION: Type 2 diabetic conditions alter P-gp function as well as expression level and correlate poorly with each other.

Immunoprotective effect of epigallocatechin-3-gallate on oral anticancer drug-induced α-defensin reduction in Caco-2 cells.

The aim of this study was to determine the effect of interaction between tegafur (FT) and epigallocatechin-3-gallate (EGCG) on the expression of α-defensins (HD-5: human α-defensin 5, HD-6: human α-defensin 6) by using a Caco-2 cell line as a model of human intestinal epithelial cells. This is the first study in which the effect of interaction of an oral anticancer drug and functional food on the innate immune system was examined. α-Defensins are abundant constituents of mouse and human paneth cells and play a role in the innate immune system in intestine. We detected HD-5 and HD-6 mRNA in Caco-2 cells and evaluated the effects of FT and EGCG on these mRNA levels. HD-5 and HD-6 mRNA levels were decreased by exposure to FT. Production of reactive oxygen species (ROS) was induced by exposure to FT as well as H2O2 exposure, and EGCG suppressed FT-induced production of ROS. Furthermore, FT-induced decrease in HD-5 and HD-6 mRNA levels was almost completely suppressed by EGCG. These results indicate that EGCG restored the decrease of α-defensins induced by FT at the transcriptional level in Caco-2 cells, suggesting that EGCG can be used as adjunctive therapy in chemotherapy.

Regulation of the expression and activity of glucose and lactic acid metabolism-related genes by protein kinase C in skeletal muscle cells.

Protein kinase C (PKC) modulators are very attractive therapeutic targets in cancer. Since most cancer cells display increased glycolysis, elucidations of the effects of PKC activation on glycolysis is necessary for the development of effective medicine. In the present study, to clarify the role of PKC in the regulation of glycolysis, we examined the effect of phorbol 12-myristate 13-acetate (PMA), a PKC activator, on the expression and activity of glucose and lactic acid metabolism-related genes in human rhabdomyosarcoma cells (RD cells). In parallel to increases in glucose uptake and mRNA levels of glucose transporters (GLUTs) induced by PMA treatment for 6 h, the hexokinase (HK) mRNA level and activity were also significantly increased in RD cells. On the other hand, a significant increase in lactate dehydrogenase (LDH) mRNA level and activity was seen when the cells were incubated with PMA for 24 h, but not for 6 or 12 h, and was associated with lactic acid production. These effects by PMA treatment were markedly suppressed by Bisindolylmaleimide (BIM), a PKC inhibitor. Furthermore, chetomin, a hypoxia-inducible factor 1 (HIF-1) inhibitor, completely abrogated the increment of LDH mRNA level and activity as well as monocarboxylate transporter (MCT) 4, a lactic acid efflux transporter. In conclusion, we found that HK and LDH activity induced by PKC activation was associated with the glucose uptake and lactic acid level and that LDH and MCT4 are modulated by a common factor, HIF-1.

Crucial residue involved in L-lactate recognition by human monocarboxylate transporter 4 (hMCT4).

BACKGROUND: Monocarboxylate transporters (MCTs) transport monocarboxylates such as lactate, pyruvate and ketone bodies. These transporters are very attractive therapeutic targets in cancer. Elucidations of the functions and structures of MCTs is necessary for the development of effective medicine which targeting these proteins. However, in comparison with MCT1, there is little information on location of the function moiety of MCT4 and which constituent amino acids govern the transport function of MCT4. The aim of the present work was to determine the molecular mechanism of L-lactate transport via hMCT4. EXPERIMENTAL APPROACH: Transport of L-lactate via hMCT4 was determined by using hMCT4 cRNA-injected Xenopus laevis oocytes. hMCT4 mediated L-lactate uptake in oocytes was measured in the absence and presence of chemical modification agents and 4,4'-diisothiocyanostilbene-2,2'-disulphonate (DIDS). In addition, L-lactate uptake was measured by hMCT4 arginine mutants. Immunohistochemistry studies revealed the localization of hMCT4. RESULTS: In hMCT4-expressing oocytes, treatment with phenylglyoxal (PGO), a compound specific for arginine residues, completely abolished the transport activity of hMCT4, although this abolishment was prevented by the presence of L-lactate. On the other hand, chemical modifications except for PGO treatment had no effect on the transport activity of hMCT4. The transporter has six conserved arginine residues, two in the transmembrane-spanning domains (TMDs) and four in the intracellular loops. In hMCT4-R278 mutants, the uptake of L-lactate is void of any transport activity without the alteration of hMCT4 localization. CONCLUSIONS: Our results suggest that Arg-278 in TMD8 is a critical residue involved in substrate, L-lactate recognition by hMCT4.

Regulation of multidrug resistance protein 2 (MRP2, ABCC2) expression by statins: involvement of SREBP-mediated gene regulation.

Multidrug resistance protein 2 (MRP2, ABCC2) is localized to the apical membrane of hepatocytes and played an important role in the biliary excretion of a broad range of endogenous and xenobiotic compounds and drugs, such as pravastatin. However, the effects of statins on MRP2 in the liver and the precise mechanisms of their actions have been obscure. The goal of this study was to determine the regulatory molecular mechanism for statin-induced MRP2 expression in hepatocytes. In vitro and in vivo studies suggested that pitavastatin increased MRP2 expression. Pitavastatin promoted liver X receptor (LXR) α/ß translocation from the cytosol to nuclei, resulting in LXR activation. Deletion and mutational analysis suggested that the potential sterol regulatory element (SRE) played a major role in the observed modulation of MRP2 expression by pitavastatin. Furthermore pitavastatin increased the protein-DNA complex, and when SRE was mutated, stimulation of the protein-DNA complex by pitavastatin was decreased. It was demonstrated that pitavastatin upregulated MRP2 expression by an SREBP regulatory pathway in hepatocytes and that the actions of statins may lead to improve the biliary excretion of MRP2 substrates.

Rapid stimulating effect of the antiarrhythmic agent amiodarone on absorption of organic anion compounds.

In a clinical setting, changes in pharmacokinetics due to drug-drug interactions can often directly affect the therapeutic safety and efficacy of drugs. Recently, interest has been shown in drug-drug interactions in the intestine. It is now recognized that changes in the functions of drug transporters substantially influence the absorption of administered drugs from the intestine. Amiodarone (AMD) is a potent drug used in the treatment of serious supraventricular and ventricular tachyarrhythmias. Despite its potent pharmacological effects, its wide clinical use is precluded by drug-drug interactions. In this study, we characterized the transporter function between AMD and various compounds in human intestinal model Caco-2 cells. AMD significantly and rapidly increased the uptake of [(3)H]estrone-3-sulfate (E-3-S) for 5 min. The apical-to-basal transport of [(3)H]E-3-S was significantly increased by AMD. The AMD-stimulated [(3)H]E-3-S uptake was inhibited by organic anion transporting polypeptide (OATP) substrates. Caco-2 cells treated with AMD showed increased OATP2B1 expression on the cell surface. AMD also increased the absorption of sulfobromophthalein (BSP), which is a typical organic anion compound, and the expression level of Oatp2b1 at the membrane in in vivo experiments. The results indicate that AMD induces OATP2B1/Oatp2b1 expression at the membrane in the intestine and enhances absorption of organic anion compounds.

Implications for better nursing practice: psychological aspects of patients undergoing post-operative wound care.

AIMS AND OBJECTIVES: To understand the psychological aspects in patients undergoing post-operative wound care and to gain insights for improving nursing practice. BACKGROUND: Very few studies have examined education on or practice of wound care with a view towards the patient's psychology. DESIGN: Descriptive exploratory qualitative study. METHODS: Four patients who had undergone open surgery of the upper gastrointestinal tract were interviewed using a semi-structured format to gain an understanding of their feelings and opinions with regard to wound care. Interview transcripts were analysed using an inductive coding approach. RESULTS: Fifteen categories of responses were finally identified from the data. Patients wanted nursing staff to observe their wound more often so that patients could recognise improvement, to have better knowledge of the patient's disease and condition, to explain the patient's situation more completely and to appropriately answer questions. Patients also said that they felt more comfortable in posing questions or concerns regarding their condition to nursing staff than to their surgeons and did so while the wounds were being taken care of by nurses. CONCLUSIONS: These findings suggested the importance of nursing staff to fully understand and to be ready to share feelings regarding a patient's postoperative condition and to have skills in properly explaining the importance of each procedure or steps in treatments that a patient must undergo. The present study also indicates that it is imperative for nursing staff to learn methods to build relationships with patients so that they can express their feelings of fear or anxiety freely to nurses. RELEVANCE TO CLINICAL PRACTICE: It is not possible to develop nursing practice without understanding psychological aspects of patients undergoing postoperative wound care.