Nalmefene, an opioid receptor modulator, aggravates atherosclerotic plaque formation in apolipoprotein E knockout mice by enhancing oxidized low-density lipoprotein uptake in macrophages.

Nalmefene, an antagonist of mu- and delta-opioid receptors and a partial agonist of kappa-opioid receptors, has shown promise in reducing alcohol consumption among patients with alcohol dependence. Opioid receptors play pivotal roles in various physiological processes, including those related to peripheral inflammatory diseases such as colitis and arthritis, as well as functions in the immune system and phagocytosis. Atherosclerosis, a chronic inflammatory disease, progresses through the phagocytosis and uptake of oxidized low-density lipoprotein (oxLDL) by macrophages in atherosclerotic plaques. Despite this knowledge, it remains unclear whether nalmefene influences the formation of atherosclerotic plaques and increases the risk of serious cardiovascular events. This study aims to elucidate the impact of nalmefene on atherosclerosis in apolipoprotein E knockout (ApoE KO) mice and peritoneal macrophages in vitro. In this experiment, 8-week-old male ApoE KO mice were fed a high-fat diet intraperitoneally administered either vehicle (saline) or nalmefene (1 mg and 3 mg kg-1 day-1) for 21 days. Oil red O-staining and immunohistochemistry with an anti-MOMA2 (monocyte/macrophage) antibody showed that a dose-dependent increase in atherosclerotic plaque formation and augmentation of macrophage-rich plaque formation in ApoE-KO mice. Further investigations focused on the effects of nalmefene on the expression of scavenger receptor CD36 in RAW264.7 cells, conducted through western blotting analysis. Nalmefene demonstrated a significant increase in CD36 protein expression in RAW264.7 cells. To explore the impact on oxidized LDL uptake in peritoneal macrophages, cells were treated with nalmefene (300 µg/mL) for 24 h, followed by the addition of DiI-labeled oxLDL (DiI-oxLDL) for 4 h. Nalmefene significantly enhanced DiI-oxLDL uptake in macrophages. Additionally, treatment with nalmefene (300 µg/mL) for 24 h decreased the mRNA expression of mu-, delta-, and kappa-opioid receptors in RAW264.7 cells. In conclusion, nalmefene may augment oxLDL uptake by macrophages through increased CD36 expression and decreased opioid receptor, thereby contributing to atherosclerotic plaque formation and vulnerability. Consequently, the use of nalmefene may be associated with an elevated risk of cardiovascular events.

Menahydroquinone-4 may play a key role in regulating CCL5 expression induced by epidermal growth factor receptor inhibitors.

Epidermal growth factor receptor (EGFR) inhibitors frequently cause severe skin rash as a side effect, which is a critical burden for patients who continuously receive drug treatments. Several recent clinical trials have shown that vitamin K is effective against these side effects; however, the underlying mechanisms remain unclear. EGFR inhibitors induce C-C motif chemokine ligand 5 (CCL5) in dermopathy. We hypothesized that menahydroquinone-4 (MKH), the active form of menaquinone-4 (MK-4, vitamin K2(20)), supplied by biosynthesis or external delivery, is essential for the suppressive effect on CCL5. The aim of this study was to explore the underlying mechanisms governing the relieving effects of MKH against skin rashes caused by EGFR inhibitors. The responses generated by EGFR inhibitors and the effect of MKH derivatives (two ester derivatives and MK-4) on them were evaluated using human skin cell lines (HaCaT and HSC-1). EGFR inhibitors downregulated UbiA prenyltransferase domain-containing protein-1 (UBIAD1, MKH synthetase) expression and MKH biosynthesis. Knockdown of UBIAD1 or γ-glutamyl carboxylase and treatment with warfarin upregulated CCL5 expression. MKH derivatives suppressed the CCL5 expression induced by EGFR inhibitors. Our data strongly suggest that MKH is involved in suppressing CCL5 expression and alleviating the skin damage caused by EGFR inhibitors.

Cationic Ester Prodrugs of Curcumin with N,N-dimethyl Amino Acid Promoieties Improved Poor Water Solubility and Intestinal Absorption.

PURPOSE: Although curcumin (Cur) has powerful pharmacological effects, its use in medicine has not been established yet. The oral bioavailability (BA) of Cur is limited because of its poor water solubility. The purpose of this study was to confirm whether cationic N,N-dimethyl amino acid esters of Cur could act as prodrugs and improve its water solubility and oral bioavailability. METHODS: Two N,N-dimethyl amino acid esters of Cur were synthesized. The hydrolysis profile of the esters was evaluated using rat and human microsomes. A pharmacokinetic study after oral administration of the Cur ester derivatives was performed in rats and compared to the administration of suspended or dissolved Cur formulation. The anti-inflammatory effects of the Cur derivatives were evaluated using macrophage RAW 264.7 stimulated with lipopolysaccharide. RESULTS: Cur ester derivatives showed > 200 mM water solubility. The derivatives were reconverted to the parent compound (Cur) after cleavage of the ester bonds by microsomal esterase, indicating that the compounds could act as Cur prodrugs. The Cur prodrugs enhanced the absolute oral bioavailability of Cur by a 9- and threefold increase of suspended and dissolved Cur administration, respectively, thereby improving intestinal absorption. Cur prodrugs strongly attenuated COX2, iNOS, and ERK phosphorylation. CONCLUSIONS: The cationic N,N-dimethyl amino acid ester prodrugs of Cur improved the water solubility of Cur and enhanced oral bioavailability in rats. These Cur prodrugs may be good candidates for developing medicinal options previously unavailable due to the poor water solubility and oral BA of Cur.

Delivery of the reduced form of vitamin K2(20) to NIH/3T3 cells partially protects against rotenone induced cell death.

Mitochondria generate energy through the action of the electron transport chain (ETC) and ATP synthase. Mitochondrial malfunction can lead to various disorders, including neurodegenerative diseases. Several reports have shown that menaquinone-4 (MK-4, vitamin K2(20)), a safe drug for osteoporosis, may improve mitochondrial function. Here, we hypothesized that the efficient delivery of menahydroquinone-4 (MKH), an active form of MK-4, could exert a supporting effect. We verified the effects of MKH delivery on mitochondrial dysfunction by using MK-4 and MKH ester derivatives in NIH/3T3 mouse fibroblast cells treated with mitochondrial inhibitors. MK-4 and MKH derivatives suppressed cell death, the decline in mitochondrial membrane potential (MMP), excessive reactive oxygen species (ROS) production, and a decrease in intrinsic coenzyme Q9 (CoQ9) induced by rotenone (ROT, complex I inhibitor). MK-4 and MKH derivatives delivered MKH to NIH/3T3 cells, acting as an effective MKH prodrug, proving that the delivered MKH may reflect the mitigation effects on ROT-induced mitochondrial dysfunction. MKH prodrugs are also effective against 3-nitropropionic acid (3-NP, complex II inhibitor) and carbonyl cyanide-m-chlorophenylhydrazone (CCCP, uncoupler)-induced cell death. In conclusion, MKH delivery may mitigate mitochondrial dysfunction by maintaining MMP, ROS, and CoQ9, indicating that MKH prodrugs may be good candidates for treating mitochondrial disorders.

Moxifloxacin induces aortic aneurysm and dissection by increasing osteopontin in mice.

Fluoroquinolones are one of the most frequently prescribed antibiotics. However, their use increases the risk of Aortic aneurysm and dissection (AAD). The mechanism underlying this effect remains unclear. AAD are caused by weakening of the aortic wall and loss of vascular smooth muscle cells. Osteopontin is involved in the occurrence and development of AAD. The aim of the present study was to examine the role of moxifloxacin, a fluoroquinolone, in the occurrence of AAD using a moderate-severity AAD mouse model. Four-week-old male C57BL/6J mice were fed a high-fat diet. At 8 weeks of age, the mice were infused with saline or angiotensin II (1000 ng kg-1 min-1) via osmotic minipumps for 4 weeks, and then orally administered water (vehicle) or moxifloxacin (30 and 100 mg kg-1 day-1) for another 3 weeks. Moxifloxacin (30 and 100 mg kg-1 day-1) induced AAD and elastin degradation in aortic tissues, as revealed by hematoxylin and eosin staining and elastica-van Gieson staining. Additionally, immunohistochemical staining and Western blot analyses showed that moxifloxacin 100 mg kg-1 day-1 decreased the protein expression of smooth muscle protein 22α, one of the markers of the contractile phenotype of vascular smooth muscle cells, in aortic tissues compared to vehicle and moxifloxacin 30 mg kg-1 day-1. Furthermore, moxifloxacin (100 mg kg-1 day-1) increased the protein expression of osteopontin and matrix metalloproteinases-2 in the aortic tissues when compared to control. Moxifloxacin may induce the onset of AAD and weakening of the aortic media by increasing the expression of osteopontin and matrix metalloproteinase-2 and decreasing that of smooth muscle protein 22α in aortic tissue.

Cationic N,N-Dimethylglycine Ester Prodrug of 2R-α-Tocotrienol Promotes Intestinal Absorption via Efficient Self-Micellization with Intrinsic Bile Acid Anion.

The intestinal absorption of hydrophobic compounds is severely influenced by their transportation rate through the unstirred water layer in the intestinal lumen. A member of the vitamin E family, α-Tocotrienol (α-T3) has remarkable pharmacological effects, but its intestinal absorption is hampered due to its hydrophobicity. Here, we prepared three ester derivatives of 2R-α-T3, and we selected a suitable prodrug compound using rat plasma and liver microsomes. The micellization profile of the selected compound in the presence of taurocholic acid (TCA) was evaluated. After gastrostomy administration of the prodrug candidate or α-T3 solution containing TCA, AUC values were determined for α-T3 in plasma obtained from bile duct-ligated rats. Among the three types in the efficiency of the reconversion to the parent drug, α-T3 N,N-dimethylglycinate (α-T3DMG) was the best prodrug; α-T3DMG formed mixed micelles via ion pairs with anionic TCA. The solubility of α-T3DMG in n-octanol/water depended on its ratio to TCA. The AUC after α-T3DMG administration to ligated rats was 2-fold higher than that after α-T3 administration, suggesting a smooth interaction with intrinsic bile acids. In conclusion, utilization of the prodrug synthesized using N,N-dimethylglycine ester may be a beneficial approach to promote intestinal absorption of α-T3 via self-micellization with intrinsic bile acid.

[Identification Methods for Pseudo-crystalline Polymorphs of Thiamine Chloride Hydrochloride, Which Transform Easily Depending on the Handling Environment].

Three forms of pseudo-crystalline polymorph of thiamine chloride hydrochloride are dependent on hydration states. We investigated how the measurement environment affects the transition of the pseudo-crystalline polymorph, and aimed to establish a reliable method of identifying the forms clearly by IR spectrophotometry. We prepared three pseudo-crystalline forms and compared their IR spectra. In the IR spectra obtained by the potassium chloride (KCl) disk method, Form II was identified based on its characteristic absorption, but Forms I and III could not be distinguished clearly. Form I transformed to Form III after mixing with undried KCl powder, and Form III transformed to Form I by simply being left in the laboratory environment. These results suggested that the reversible transformation between Forms I and III occurred depending on the hydration status during the process of measurement, as measured by the shift in the absorption wavenumber of the primary alcohol stretching vibration. In addition, Forms I and III could not be distinguished clearly by the X-ray powder diffraction and their crystalline forms were similar plate crystals. However, in the IR spectra by the attenuated total reflection (ATR) method, the three forms could be identified based on each characteristic absorption. In summary, the ATR method does not require pretreatment for sample analysis, can be performed quickly, and is thus suitable to identify crystalline polymorph forms such as pseudo-crystalline polymorphs of thiamine chloride hydrochloride, which transform easily depending on the hydration status in a measurement environment.

Characteristics of bull sperm acrosome associated 1 proteins.

An atypical distribution of sperm acrosomal tyrosine-phosphorylated proteins [which include sperm acrosome associated 1 (SPACA1) proteins] may be related to the relatively lesser pregnancy rates when semen of some bulls are used for artificial insemination (AI). There may also be these associations with bull SPACA1 proteins that are translocated from the equatorial segment to the anterior part in the acrosomes during sperm maturation in the normally functioning epididymis. The aim of the present study, therefore, was assessment of the characteristics of bull SPACA1 proteins. Results from immunocytochemical evaluations indicate there were large variations in sperm percentages with typically distributed SPACA1 proteins in acrosomes of cauda epididymal sperm samples (7%-95%). These values were positively correlated with percentages of epididymal spermatozoa with typically distributed acrosomal tyrosine-phosphorylated proteins (r=0.8564, P<0.001). Results indicate there are individual differences in translocation of SPACA1 proteins in the epididymis during sperm maturation, and that SPACA1 protein is one of the main determinants for the typical distribution of acrosomal tyrosine-phosphorylated proteins. In addition, conception rates as a result of AI using cryopreserved spermatozoa tended to be associated with percentages of epididymal spermatozoa with typically distributed SPACA1 proteins. Results from sucrose gradient centrifugation fractionation experiments indicate SPACA1 proteins are sperm membrane raft-associated proteins. Based on these results, it is hypothesized that there is an association between bull subfertility when semen is used for AI and epididymal dysfunctions in the arrangement of membrane lipid rafts during sperm maturation.

Enantioselective Acetalization by Dynamic Kinetic Resolution for the Synthesis of γ-Alkoxybutenolides by Thiourea/Quaternary Ammonium Salt Catalysts: Application to Strigolactones.

Although acetalization is a fundamental transformation in organic synthesis, intermolecular asymmetric acetalization remains an unsolved problem. In this study, a thiourea-ammonium hybrid catalyst was shown to promote the O-alkylation of enols with a racemic γ-chlorobutenolide through dynamic kinetic resolution to give chiral acetals with good enantioselectivity. The catalyst simultaneously activates both the nucleophile and electrophile in a multifunctional manner. This method was applied to the asymmetric synthesis of several strigolactones. DFT calculations suggest that hydrogen-bonding interactions between the chlorine atom of the γ-chlorobutenolide and the tosylamide hydrogen atom of the catalyst, as well as other types of noncovalent catalyst-substrate interactions, are crucial for achieving high stereoselectivity.

Enhancement of the Photofunction of Phosphorescent Pt(II) Cyclometalated Complexes Driven by Substituents: Solid-State Luminescence and Circularly Polarized Luminescence.

Ligand functionalization is an attractive strategy for enhancing the performance of metal-based phosphorescent emitters. Here, we report the synthesis and characterization of cyclometalated Pt(II) complexes Pt3 and Pt4 containing organosilyl-substituted (2-(2-thienyl)pyridine) ligands and compare their properties with those of Pt1 (no substituent) and Pt2 (organocarbon substituent). The photophysical characteristics of these molecules, including their absorption and phosphorescence spectra, phosphorescence quantum yield and lifetime, were investigated. The molecular structures were revealed by X-ray diffraction analysis. Under UV light irradiation, Pt2-Pt4 emitted intense orange phosphorescence in the solid state because of the bulkiness of their side chains (up to ΦP: 0.49). Optically pure (-)-(S)Si-Pt4 and (+)-(R)Si-Pt4 were prepared using the optically active ligands (+)-L4 and (-)-L4, respectively. The chiroptical properties of (+)-(R)Si-Pt4, which has an asymmetric silicon atom, were investigated. Circular dichroism and circularly polarized luminescence measurements showed that these structural motifs are suitable for applications in chiroptical phosphorescent materials.

Peritonitis due to Moraxella osloensis: A case report and literature review.

A-26-year-old man was admitted to our hospital with diffuse abdominal pain, nausea, and vomiting. He had a history of malignant nephrosclerosis, for which he had been receiving peritoneal dialysis (PD) for the past 14 months. His PD effluent was cloudy and turbid (white blood cell count, 10,528/µL; neutrophils 95.2%). A Gram-negative coccobacillus was isolated from peritoneal fluid culture. However, the organism could not be identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) (Vitek MS, bioMérieux), but was identified as Moraxella osloensis by the 16S rRNA gene sequencing. He was successfully treated with intraperitoneal cefazolin therapy for 3 weeks without removing the intra-abdominal catheter. A literature review revealed three previous case reports all of which were diagnosed by MALDI Biotyper (Bruker Daltonics), suggesting that the identification of M. osloensis may vary depending on the type of MALDI-TOF MS system. In conclusion, we experienced a case of M. osloensis infection in a PD patient, which was successfully treated by antibiotic treatment, without removing the PD catheter.

Chiral Sensing Using Circularly Polarized Luminescence of Bis(phenanthroline dicarboxylic acid) EuIII Complex Induced by Allosteric-type Interaction with Amino Acid Molecules.

[Eu(pda)2 ]- and [Eu(bda)2 ]- (pda=1,10-phenanthroline-2, 9-dicarboxylic acid; bda=2,2' bipyridine 5,5'-dicarboxylic acid) have an achiral D2d structure in crystals. These complexes exhibit circularly polarized luminescence (CPL) in water containing chiral amino acids. In this work, induced CPL of [Eu(pda)2 ]- and [Eu(bda)2 ]- in water solutions containing a mixture of d- and l- amino acids were examined. Plots of glum values of the induced CPL as a function of mol-fraction of l- and d- arginine reveal that [Eu(pda)2 ]- favors homo-association ([Eu(pda)2 ]- -(l-arginine)2 or [Eu(pda)2 ]- -(d-arginine)2 ) over hetero-association {[Eu(pda)2 ]- -(l-arginine)⋅(d-arginine)}. This suggests that association of an arginine molecule induces a structural change in [Eu(pda)2 ]- to promote chiral selective association to another arginine, i.e., homo-allosteric association. On the other hand, the system of [Eu(pda)2 ]- with histidine favors hetero-allosteric association over homo-association. No allosteric effect is recognized in CPL from [Eu(bda)2 ]- .

Reconsideration of the evaluation criteria for bull ejaculated sperm motility in the context of rotation.

Progressive movement of spermatozoa has conventionally been regarded as a good indicator of motility. However, bull spermatozoa exhibit two types of progressive movement: progressive/planar movement without rotation and progressive/helical movement with rotation. The aim of this study was to reconsider the evaluation criteria of bull ejaculated sperm motility in the context of rotation. Here, we compared the movement patterns of ejaculated spermatozoa with relatively high and low protein kinase A (PKA)-mediated signaling activities, because sperm motility is positively regulated by PKA-mediated signaling activities. We prepared sperm samples with high and low PKA-mediated signaling activities by suspending spermatozoa in media containing either the stimulator (NaHCO3) or inhibitor (KH-7) of adenylyl cyclase 10, and we then investigated movement patterns and relative velocities using a microscopic high-speed camera and recording system. In the control medium without NaHCO3 and KH-7, most spermatozoa exhibited round/planar movement without rotation and asymmetrical bends in the principal pieces. NaHCO3 significantly promoted changes in movement patterns from round/planar movement to progressive/planar movement (without rotation) as well as symmetrization of flagellar bends and increased relative velocities. KH-7 significantly increased spermatozoa exhibiting progressive/helical movement (with rotation), decreased relative velocities, and symmetrized flagellar bends with a reduction in their size. These indicate that progressive/planar movement (without rotation) and fast movement characterize the movement patterns of bull ejaculated spermatozoa with high PKA-mediated signaling activities. A sign of reduced PKA-mediated signaling activity is not only slow movement but also helical movement (with rotation). Thus, it is beneficial to add a new parameter of "rotation" to the evaluation criteria of bull ejaculated sperm motility.

[Cardiac Perforation after Pacemaker Implantation;Report of a Case].

A 71-year-old woman was diagnosed with sick sinus syndrome (SSS) upon her cardiogenic cerebral embolism and underwent pacemaker implantation. Active fixation leads were positioned at the right atrial appendage and ventricular septum. Twenty-one days later at her routine checkup, she was asymptomatic and there were no signs of cardiac tamponade or pacing failure. But echocardiography and computed tomography revealed a large amount of pericardial effusion due to the lead perforation. We performed open drainage because her anticoagulant could not be stopped for her history of cerebral infarction. Upon surgery, 400 ml of hemorrhagic pericardial effusion was drained and we found a lead tip penetrating through the right atrial appendage. We should carefully observe for lead perforation after pacemaker implantation, especially when using the active fixation lead.

Age-related changes in mRNA levels of hepatic transporters, cytochrome P450 and UDP-glucuronosyltransferase in female rats.

Hepatic transporters and metabolic enzymes affect drug pharmacokinetics. Limited information exists on the alteration in mRNA levels of hepatic transporters and metabolic enzymes with aging. We examined the effects of aging on the mRNA levels of representative hepatic drug transporters and metabolic enzymes by analyzing their levels in 10-, 30- and 50-week-old male and female rats. Levels of mRNA of drug transporters including multidrug resistance protein (Mdr)1a, multidrug resistance-associated protein (Mrp)2, breast cancer resistance protein (Bcrp) and organic anion-transporting polypeptide (Oatp)1a1, and the metabolic enzymes cytochrome P450 (CYP)3A1, CYP3A2 and UDP-glucuronosyltransferase (UGT)1A1 were analyzed using real-time reverse transcriptase polymerase chain reaction. The mRNA levels of transporters in male rats did not decrease with age, while the mRNA levels of Bcrp and Oatp1a1 in female rats decreased with age. The mRNA levels of CYP3A1 and CYP3A2 in male rats were higher than those in female rats. The mRNA levels of metabolic enzymes decreased with age in female but not male rats. In particular, the mRNA levels of UGT1A1 in 10-week-old female rats were higher than those in male rats. mRNA expression of hepatic transporters and metabolic enzymes are more susceptible to aging in female than male rats. The age-related decreases in the mRNA levels of Bcrp, Oatp1a1, CYP3A1 and CYP3A2 in female rats may affect the metabolism and transport of substrates. This study showed that aging affected the mRNA expression of hepatic transporters and metabolic enzymes in rats.

Effects of ginsenosides on the expression of cytochrome P450s and transporters involved in cholesterol metabolism.

An extract from red ginseng (steamed and dried roots of Panax ginseng C.A. Meyer; RGE) has been shown to promote cholesterol metabolism in the liver. We have reported that RGE induced the hepatic expression of cytochrome P450 (CYP)7A1, involved in cholesterol metabolism. Other cholesterol metabolism-related proteins, such as CYP8B1, CYP27A1, multidrug resistance-associated protein (MRP)2, MRP3, and Na(+) taurocholate cotransporting polypeptide (NTCP), are involved in cholesterol metabolism. The purpose of this study was to clarify whether RGE affected mRNA expression of cholesterol metabolism-related CYPs and transporters in the liver of hypercholesterolemic rats and rat primary hepatocytes. In-vivo studies showed little differences in CYP8B1, CYP27A1, MRP2, MRP3, and NTCP mRNA expression levels between hypercholesterolemic rats with or without RGE treatments. However, the disruption of the membrane localization of MRP2 was suppressed by RGE treatments in hypercholesterolemic rats. In-vitro studies using rat primary hepatocytes showed upregulation of CYP8B1 and MRP2 mRNA by the addition of RGE (100 and 500 µg/mL). We further examined which ginsenosides contributed to the upregulation of CYP8B1 and MRP2 mRNA levels. Ginsenoside Re enhanced the mRNA level of CYP8B1, whereas ginsenosides Rb2 and Rg2 enhanced MRP2 mRNA levels. These results suggest that the in-vitro exposure of hepatocytes to RGE or some ginsenosides could lead to upregulation of CYP8B1 and MRP2, resulting in the alteration of biosynthesis and disposition of bile acids.

Increased effects of ginsenosides on the expression of cholesterol 7α-hydroxylase but not the bile salt export pump are involved in cholesterol metabolism.

An extract from red ginseng [steamed and dried roots of Panax ginseng C.A. Meyer (RGE)] has been shown to have various actions on physiological functions. The mechanisms by which RGE promotes cholesterol metabolism in the liver are unclear, but RGE decreases the plasma levels of cholesterol. We investigated whether RGE affected the mRNA expression of cholesterol metabolism-related proteins such as cytochrome P450 (CYP)7A1 and bile salt export pump (BSEP) in the liver in hypercholesterolemic rats and rat primary hepatocytes. In-vivo studies showed the upregulation of CYP7A1 mRNA in hypercholesterolemic rats treated with RGE. Treatment with RGE exhibited decreased ratios of low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol compared with hypercholesterolemia without RGE. In-vitro studies also showed the upregulation of CYP7A1 mRNA and protein levels by the addition of RGE to rat primary hepatocytes. The mRNA levels of BSEP exhibited few changes. The sustained levels of the liver X receptor (LXR) in vivo and the increased levels of LXR in vitro on RGE treatment could be involved in the upregulation of CYP7A1. To clarify the effects of 11 ginsenosides including RGE on the mRNA levels of CYP7A1 and BSEP, we performed in-vitro experiments using rat primary hepatocytes. The ginsenosides Ro, Rg3, Re, Rg1, and Rg2 exhibited increased mRNA levels of CYP7A1. These results suggest that several ginsenosides including RGE promoted cholesterol metabolism due to upregulation of CYP7A1.

Changes in mRNA expression of ABC and SLC transporters in liver and intestines of the adjuvant-induced arthritis rat.

In this study, a real-time reverse transcription-polymerase chain reaction was used to determine the effects of adjuvant-induced arthritis (AA) on the amounts of mRNA of 12 types of rat ATP-binding cassette (ABC) and solute carrier (SLC) transporters in the liver and small intestine, 7 (D7) and 21 days (D21) after the injection of adjuvant. There were no significant differences in mRNA levels of ABC and SLC transporters between the livers of AA and control rats on D7, except in the case of Mdr1a. However, levels of Mdr1a, Mrp2 and Oatp SLC transporters were significantly lower in AA than in the control livers on D21. In contrast, the mRNA levels of several ABC and SLC transporters, especially Mrp2, Bcrp, LAT2 and Oatp1a5, were significantly lower in the small intestines of AA rats compared with the controls on D7, though there were no significant differences by D21. The time-dependent alterations in mRNA levels of the pregnane X receptor, but not the constitutive androstane receptor, in the liver and intestine were similar to the changes in mRNA levels of most transporters examined. The present study showed that AA was associated with reduced mRNA expression of several ABC and SLC transporters in the liver and small intestine, but that the time courses of the effects of AA on mRNA expression differed between the liver and small intestine. These results raise the possibility of a functional change of the transporters of liver and intestine in AA rats.

[Discharge support practices that strengthened the regional alliances--analysis of two cases effectively used of the discharge conference prior to a hospital discharge].

The discharge support system has been constructed in our hospital. This system clarified a flow of regional alliances such as screening, discharge support, and conference with multi-occupational category. We report two cases which received a continued caring by using this system. Patient's information, problems, and mutual goals were shared after the construction of the system. An effective use of conference prior to a hospital discharge made it possible that people in the multi-occupational category could cooperate and use their own skills whenever required to get the job done. This time, we have enhanced cooperation with the staff in the region because we were able to give guidance in collaboration with the patients, their family and care manager.