Alteration of the intravenous and oral pharmacokinetics of valsartan via the concurrent use of gemfibrozil in rats.

The present study aimed to examine the potential pharmacokinetic drug interaction between valsartan and gemfibrozil. Compared with the control given valsartan (10 mg/kg) alone, the concurrent use of gemfibrozil (10 mg/kg) significantly (p < 0.05) increased the oral exposure of valsartan in rats. In the presence of gemfibrozil, the Cmax and AUC of oral valsartan increased by 1.7- and 2.5-fold, respectively. Consequently, the oral bioavailability of valsartan was significantly higher (p < 0.05) in the presence of gemfibrozil compared with that of the control group. Furthermore, the intravenous pharmacokinetics of valsartan (1 mg/kg) was also altered by pretreatment with oral gemfibrozil (10 mg/kg). The plasma clearance of valsartan was decreased by two-fold in the presence of gemfibrozil, while the plasma half-life was not altered. In contrast, both the oral and intravenous pharmacokinetics of gemfibrozil were not affected by the concurrent use of valsartan. The cellular uptake of valsartan and gemfibrozil was also investigated by using cells overexpressing OATP1B1 or OATP1B3. Gemfibrozil and gemfibrozil 1-O-ß glucuronide inhibited the cellular uptake of valsartan with IC50 values (µm) of 39.3 and 20.4, respectively, in MDCK/OATP1B1, while they were less interactive with OATP1B3. The cellular uptake of gemfibrozil was not affected by co-incubation with valsartan in both cells. Taken together, the present study suggests the potential drug interaction between valsartan and gemfibrozil, at least in part, via the OATP1B1-mediated transport pathways during hepatic uptake. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Heavy Hymenolepis nana infection possibly through organic foods: report of a case.

We encountered a patient with heavy Hymenolepis nana infection. The patient was a 44-year-old Korean man who had suffered from chronic hepatitis (type B) for 15 years. A large number of H. nana adult worms were found during colonoscopy that was performed as a part of routine health screening. The parasites were scattered throughout the colon, as well as in the terminal ileum, although the patient was immunocompetent. Based on this study, colonoscopy may be helpful for diagnosis of asymptomatic H. nana infections.

Expression and characterization of α-methylacyl CoA racemase from Anisakis simplex larvae.

Larval excretory-secretory products of Anisakis simplex are known to cause allergic reactions in humans. A cDNA library of A. simplex 3rd-stage larvae (L3) was immunoscreened with polyclonal rabbit serum raised against A. simplex L3 excretory-secretory products to identify an antigen that elicits the immune response. One cDNA clone, designated as α-methylacyl CoA racemase (Amacr) contained a 1,412 bp cDNA transcript with a single open reading frame that encoded 418 amino acids. A. simplex Amacr showed a high degree of homology compared to Amacr orthologs from other species. Amacr mRNA was highly and constitutively expressed regardless of temperature (10-40℃) and time (24-48 hr). Immunohistochemical analysis revealed that Amacr was expressed mainly in the ventriculus of A. simplex larvae. The Amacr protein produced in large quantities from the ventriculus is probably responsible for many functions in the development and growth of A. simplex larvae.

Charging effect in Au nanoparticle memory device with biomolecule binding mechanism.

Organic memory device having gold nanoparticle (Au NPs) has been introduced in the structure of metal-pentacene-insulator-silicon (MPIS) capacitor device, where the Au NPs layer was formed by a new bonding method. Biomolecule binding mechanism between streptavidin and biotin was used as a strong binding method for the formation of monolayered Au NPs on polymeric dielectric of poly vinyl alcohol (PVA). The self-assembled Au NPs was functioned to show storages of charge in the MPIS device. The binding by streptavidin and biotin was confirmed by AFM and UV-VIS. The UV-VIS absorption of the Au NPs was varied at 515 nm and 525 nm depending on the coating of streptavidin. The AFM image showed no formation of multi-stacked layers of the streptavidin-capped Au NPs on biotin-NHS layer. Capacitance-voltage (C-V) performance of the memory device was measured to investigate the charging effect from Au NPs. In addition, charge retention by the Au NPs storage was tested to show 10,000 s in the C-V curve.

Characteristics and trends in the incidence of inflammatory bowel disease in Korean children: a single-center experience.

BACKGROUND: Inflammatory bowel disease (IBD) is rare in Asian children and few reports on pediatric IBD have appeared. AIMS: We, therefore, investigated the incidence trends and clinical characteristics of pediatric IBD in Korea. METHODS: We enrolled 48 children with Crohn's disease (CD) and 14 children with ulcerative colitis (UC) from 1996 to 2007. Trends in annual enrollment and clinical characteristics were retrospectively evaluated by medical record review. RESULTS: During the 12 years of observation, the number of new enrollments gradually increased. CD showed male predominance (33 boys, 15 girls), but more females presented with UC (4 boys, 10 girls). A relevant family history was observed in 3 (4.9%) of the 61 unrelated families. The most common presenting symptom was abdominal pain (67%) in CD and hematochezia (93%) in UC. Growth delay was observed in 10% of CD patients, but not in any of the UC patients. In CD, colonic involvement occurred in 87% of patients, ileal involvement in 87%, and both the small bowel and colon were affected in 75%. With UC, pancolitis occurred in 43% of patients, left-sided colitis in 36%, and proctitis in 21%, including all three patients with appendiceal orifice inflammation. The most frequent disease behavior was inflammatory in 85% of patients, but perianal fistula was noted in 50% of CD patients. CONCLUSION: This study showed that the incidence of pediatric IBD has been rapidly increasing in Korea in recent years. Relevant family history is less prevalent and phenotypic expression differs from what is seen in Western countries.

Synthesis and antimicrobial activity of 7 alpha-amino-23,24-bisnor-5 alpha-cholan-22-ol derivatives.

A series of 7 alpha-aminobisnorsteroids were synthesized and their in vitro antimicrobial activity was evaluated regarding Gram-positive and Gram-negative bacteria. The stereoselective reductive amination of 7-ketosteroid 3 with NH(4)OAc, in the presence of NaBH(3)CN, afforded a high yield of 7 alpha-aminosteroid 4. The 3,7-diaminobisnorsteroids were obtained by the reductive amination of 4 with NH(4)OT(f), Boc-spermidine, and Boc-spermine. 3 alpha,7 alpha-Diaminobisnorsterol dihydrochloride 15 showed the highest antimicrobial activity against Streptococcus pyogenes 308 A with a MIC value of 1.6 microg/mL. Hemolytic activities of the compounds 13-20 were determined. Compound 13 showed MHC value at 100 microg/mL.

Controlled Delivery of Extracellular ROS Based on Hematoporphyrin-Incorporated Polyurethane Film for Enhanced Proliferation of Endothelial Cells.

The principle of photodynamic treatment (PDT) involves the administration of photosensitizer (PS) at diseased tissues, followed by light irradiation to produce reactive oxygen species (ROS). In cells, a moderate increase in ROS plays an important role as signaling molecule to promote cell proliferation, whereas a severe increase of ROS causes cell damage. Previous studies have shown that low levels of ROS stimulate cell growth through PS drugs-treating PDT and nonthermal plasma treatment. However, these methods have side effects which are associated with low tissue selectivity and remaining of PS residues. To overcome such shortcomings, we designed hematoporphyrin-incorporated polyurethane (PU) film induced generation of extracellular ROS with singlet oxygen and free radicals. The film can easily control ROS production rate by regulating several parameters including light dose, PS dose. Also, its use facilitates targeted delivery of ROS to the specific lesion. Our study demonstrated that extracellular ROS could induce the formation of intracellular ROS. In vascular endothelial cells, a moderated increase in intracellular ROS also stimulated cell proliferation and cell cycle progression by accurate control of optimum levels of ROS with hematoporphyrin-incorporated polymer films. This modulation of cellular growth is expected to be an effective strategy for the design of next-generation PDT.

Characterization of the physicochemical properties of KRK-701P.

KRK-701P is a broad-spectrum antibiotic with methicillin-resistant antibacterial activity. The objective of this preformulation study was to determine the physicochemical properties of KRK-701P. The n-octanol-to-water partition coefficients of KRK-701P were 0.448 at pH 4 and 2.546 at pH 8. One crystal form and one amorphous form of KRK-701P were isolated by recrystallization and characterized by differential scanning calorimetry, powder X-ray diffractometry and thermogravimetric analysis. After storage for 1 month at 0% RH (silica gel, 20 °C), 52% RH (saturated solution of Na2Cr2O7.2H2O/20 °C) and 95% RH (saturated solution of Na2HPO4/20 °C), the two forms were not transformed.

Differential diagnosis of colorectal polyps with narrow band imaging colonoscopy without magnification.

BACKGROUND/AIMS: Narrow band imaging (NBI) endoscopy can be used for gross differentiation between the types of colonic polyps. This study was conducted as a retrospective study for estimation of the interobserver and intra-observer agreement of the pit pattern of the mucosal surface and the accuracy of histology prediction. METHODS: A total of 159 patients underwent complete colonoscopy and 219 polyps examined by NBI endoscopy without magnification were assessed. Interobserver and intra-observer agreement were calculated by investigators in each group for determination of the surface pattern and prediction of histology based on the modified Kudo's classification using intraclass correlation coefficient. RESULTS: Interobserver agreement for the surface pit pattern and prediction of polyp type was 0.84 and 0.73 in experienced endoscopists, and 0.86 and 0.62 in trainees, respectively. Intra-observer agreement for the surface pit patterns and prediction of polyp type was 0.81, 0.83, 0.85, 0.83, 0.56, 0.84, 0.51, 0.83, and 0.71; and 0.71, 0.70, 0.82, 0.54, 0.72, 0.37, 0.51, 0.34, and 0.30, respectively. The diagnostic accuracy for prediction of polyp type was 69.4% for experienced endoscopists and 72.9% for trainees. CONCLUSIONS: NBI endoscopy without magnification showed fairly good inter and intra-observer agreement for the pit pattern of the mucosal surface and the accuracy of histology prediction; however, it had some limitation for differentiation of colon polyp histologic type. Training and experience with NBI is needed for improvement of accuracy.

Successful endoscopic mucosal resection of a low esophageal carcinoid tumor.

Esophageal carcinoid tumors remain some of the rarest of all carcinoid tumors, with only several cases previously reported in the literature. The endoscopic mucosal resection of selected carcinoid tumors has been shown to be a valid, safe, and effective method of treatment. Endoscopic ultrasonography is the technique of choice to select patients eligible for endoscopic resection. Here, we report successful endoscopic mucosal resection of a low esophageal carcinoid tumor and review the relevant literature. The present case is the first reported case of esophageal carcinoid tumor in Korea.

Synthesis and antimicrobial activity of 7-fluoro-3-aminosteroids.

A series of 7-fluoro-3-aminosteroids were synthesized and their in vitro antimicrobial activities were evaluated against Gram-positive and Gram-negative bacteria. The nucleophilic fluorination of several 7beta-hydroxysteroids by diethylaminosulfur trifluoride in n-pentane, followed by reductive amination of the resulting 7-fluoro-3-ketosteroids with spermidine in the presence of NaBH(3)CN, afforded 7-fluoro-3-aminosteroids in high yield. Compound 25 showed the highest antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, and Escherichia coli.

A serological survey of Dirofilaria immitis infection in pet dogs of Busan, Korea, and effects of chemoprophylaxis.

The status of Dirofilaria immitis infection was assessed in pet dogs of Busan, Korea, and chemoprophylactic effects of microfilaricidal medication were evaluated. A total of 294 pet dogs older than 6 mo were examined, 217 of which had been maintained indoors, and 77 had been kept outdoors. The SnapR kit and direct microscopic examinations of the peripheral blood were used. The mean overall parasite positive rates were 10.2% and 6.5%, respectively. Outdoor dogs evidenced adult worm infection rate of 31.2% and microfilaria infection rate of 18.2%. The indoor dogs, however, evidenced adult worm infection rate of 2.8% and microfilaria infection rate of 2.3%. The prevalence in males was more than 2 times that of females. The changing pattern of infection rates by age evidenced a gradual increase, from 2- to 6-year-old dogs, after which, a decrease in infection rates was noted. With regard to chemoprophylaxis, the infection rates of complete and incomplete chemoprophylaxis groups were found to be 2-3 times lower than that of the non-chemoprophylaxis group. The results of the present study indicate that the risk of exposure to D. immitis in pet dogs is quite high, particularly in male outdoor dogs, and chemoprophylactic measures were quite effective.

Cloning and expression of trypsin-encoding cDNA from Blattella germanica and its possibility as an allergen.

In this study, the trypsin gene (bgtryp-1) from the German cockroach, Blattella germanica, was cloned via the immunoscreening of patients with allergies to cockroaches. Nucleotide sequence analysis predicted an 863 bp open reading frame which encodes for 257 amino acids. The deduced amino acid sequence exhibited 42-57% homology with the serine protease from dust mites, and consisted of a conserved catalytic domain (GDSGGPLV). bgtryp-1 was determined by both Northern and Southern analysis to be a 0.9 kb, single-copy gene. SDS-PAGE and Western blotting analyses of the recombinant protein (Bgtryp-1) over-expressed in Escherichia coli revealed that the molecular mass of the expressed protein was 35 kDa, and the expressed protein was capable of reacting with the sera of cockroach allergy patients. We also discussed the possibility that trypsin excreted by the digestive system of the German cockroach not only functions as an allergen, but also may perform a vital role in the activation of PAR-2.

Expressed sequence tags analysis of Blattella germanica.

Four hundred and sixty five randomly selected clones from a cDNA library of Blattella germanica were partially sequenced and searched using BLAST as a means of analyzing the transcribed sequences of its genome. A total of 363 expressed sequence tags (ESTs) were generated from 465 clones after editing and trimming the vector and ambiguous sequences. About 42% (154/363) of these clones showed significant homology with other data base registered genes. These new B. germanica genes constituted a broad range of transcripts distributed among ribosomal proteins, energy metabolism, allergens, proteases, protease inhibitors, enzymes, translation, cell signaling pathways, and proteins of unknown function. Eighty clones were not well-matched by database searches, and these represent new B. germanica-specific ESTs. Some genes which drew our attention are discussed. The information obtained increases our understanding of the B. germanica genome.

Infection status of Clonorchis sinensis in residents of Hamyang-gun, Gyeongsangnam-do, Korea.

Oriental liver fluke (Clonorchis sinensis) infection was surveyed among residents of Hamyang-gun, Gyeongsangnam-do, Korea during the period of January 2001 to March 2002. Total 1,041 stool samples were collected from residents who visited Public Health Center and its branches in Hamyang-gun and examined using formalin-ether sedimentation method. The overall egg positive rate was 16%, male showing higher positive rate (21%) than female (10%). The age group of 30 to 50 years had the highest egg positive rate of C. sinensis from 20% to 22%. The positive examinees were treated with praziquantel and educated individually to prevent reinfection. Egg positive rate in this area was decreased when compared with results recorded in the past, however, still remained more than 10%. This study suggests that periodic examination, treatment as well as education of residents should be continued and systematized.

A case of acute gastric anisakiasis provoking severe clinical problems by multiple infection.

Acute gastric anisakiasis with multiple anisakid larvae infection is reported. A 68-year-old woman residing in Busan, Korea, had epigastric pain with severe vomiting about 5 hours after eating raw anchovies. Four nematode larvae penetrating the gastric mucosae in the great curvature of the middle body and fundus were found and removed during gastro-endoscopic examination. Another one thread-like moving larva was found in the great curvature of upper body on the following day. On the basis of their morphology, the worms were identified as the 3rd stage larvae of Anisakis simplex. This case is acute gastric anisakiasis provoking severe clinical problems by the multiple infection and the greatest number of anisakid larvae found in a patient in Korea.

The intestinal parasite infection status of inhabitants in the Roxas city, The Philippines.

We carried out a small-scale survey to investigate the status of intestinal protozoa and helminthes infection of inhabitants in Roxas city, Mindoro, the Philippines. Total 301 stool samples were subjected to the formalin-ether concentration method for the detection of helminth ova and protozoan cysts. The overall positive rate was 64.5%, and that of male and female were 56.6% and 72.5%, respectively. The highest infected helminth was Ascaris lumbricoudes (51.2%), followed by Trichuris trichiura (27.6%), hookworm (8.0%) and Enterobius vermicularis (0.3%). The protozoa infection status revealed that Entamoeba coli was the most frequent (15.0%). Iodoamoeba buetschlii and E. histolytica were found but few. The multiple infection more than two parasites was 29.6%, and double infection with A. lumbricoides and T. trichiura was most common. The intestinal helminth infections were highly prevalent in this area, according to this result, and we concluded that anthelminthic drugs should be given to inhabitants, especially to children of 1 to 15 years-old.

Syntheses of 1beta-methylcarbapenems bearing 5-methyl-4-hydroxypyrrolidinone.

A new series of 1beta-methylcarbapenems 1a-d bearing 5-methyl-4-mercaptopyrrolidinone rings has been prepared and evaluated for in vitro antibacterial activity and pharmacokinetic parameters. Most compounds showed excellent antibacterial activity and high stability to dehydropeptidase-1. We have synthesized optically active 5-methyl-4-hydroxypyrrolidinones from enantiomerically pure aziridine esters.

Egg positive rate of Enterobius vermicularis of primary school children in Geoje island.

The status of pinworm (Enterobius vermicularis) egg positive rate of primary school children in Geoje island was investigated by using adhesive cellotape anal swap method, in September, 2002. Total egg positive rates of E. vermicularis were 9.8% (74/754) and those of male and female were 10.8% and 8.7%, respectively. Among three schools examined, Myeongsa primary school showed the highest egg positive rate (12.6%) followed by Yeoncho [9.8% (26/266)] and Geoje [9.1% (35/385)]. As for the age groups, the 2nd grade had the highest egg positive rate (15.3%), whereas the 5th grade showed the lowest egg positive rate (2.6%). The above result led us to confirm that the egg positive rates of E. vermicularis in primary school children in Geoje island were not significantly different from the those in the whole country including urban and rural areas, showing more than 10%.