Evaluation of renovated double J stents using ureter models with and without stenosis.

PURPOSE: Commercial double J stents (DJS) have a uniform shape regardless of the specific nature of various ureteral diseases. We tested renovated DJS and compared them with conventional DJS using ureter models. METHODS: One straight ureter model included stenosis at the distal ureter near the ureterovesical junction and the other did not. We used conventional DJS and renovated 5- and 6-Fr soft DJS for ureter stones and 6-, 7-, and 8.5-Fr hard DJS for tumors. The DJS comprised holes in the upper, middle, or lower one-third of the shaft (length, 24 cm; 2-cm-diameter coils at both ends). More holes were created along the shaft based on the ureteral disease location. Conventional DJS had holes spaced 1 cm apart along the shaft. Renovated DJS had holes spaced 1 cm apart along the shaft with 0.5-cm intervals on the upper, middle, or lower one-third of the shaft. Urine flow was evaluated. RESULTS: As the DJS diameter increased, the flow rate decreased. The flow rates of DJS with holes in the lower shaft were relatively lower than those of conventional DJS and DJS with holes in the upper and middle shafts. In the ureter model without stenosis, 6-, 7-, and 8.5-Fr renovated stents exhibited significantly higher flow rates than conventional stents. In the ureter model with stenosis, 5-, 6-, 7-, and 8.5-Fr renovated stents did not exhibit significantly higher flow rates than conventional stents. CONCLUSION: Renovated stents and conventional stents did not exhibit significant differences in urine flow with stenosis.

Optimal thrombin injection method for the treatment of femoral artery pseudoaneurysm.

BACKGROUND: Iatrogenic femoral artery pseudoaneurysm (IFP) incidence is increasing with increase in diagnostic and therapeutic angiography, and so, the less invasive percutaneous thrombin injection (PTI) is the most widely used treatment. Moreover, studies that minimize PTI complications and highlight therapeutic effects are lacking. OBJECTIVES: This study performed in vitro thrombosis modeling of pseudoaneurysms and analyzed thrombosis within and thromboembolism outside the sac during thrombin injection. METHODS: We evaluated PTI in terms of thrombin injection location (at the junction of the IFP sac and neck, the center, and the dome, located farthest from the neck of the sac), thrombin injection time (5 and 8 seconds), and blood flow rate (ranging from 210 mL/min to 300 mL/min). Porcine blood was used as the working fluid in this study. RESULTS: Thrombin injection at the junction of the IFP sac and the pseudoaneurysm neck led to less thrombosis within the sac but substantial thrombi consistently outside the sac, whereas thrombin injected at the sac center mostly led to complete thrombosis within the sac, preventing further blood flow into the sac and reducing likelihood of thrombi outside the sac. A longer thrombin injection time enhanced the therapeutic effect and decreased the possibility of thromboembolism. Thromboembolism occurred more frequently at flow rates of >240 mL/min. CONCLUSION: The thrombin injection site in a pseudoaneurysm significantly influences thrombogenesis within and thromboembolism outside the sac. Thus, slow and deliberate injection of thrombin into the center of the sac could potentially reduce complications and enhance treatment efficacy.

Effect of Dialysis on Aryl Hydrocarbon Receptor Transactivating Activity in Patients with Chronic Kidney Disease.

PURPOSE: Elevated aryl hydrocarbon receptor (AhR) transactivating (AHRT) activity and uremia in chronic kidney disease (CKD) may interact with each other, further complicating the disease course. In this study, we prospectively estimated serum AHRT activity using a highly sensitive cell-based AhR-dependent luciferase activity assay in CKD patients and compared differences therein according to treatment modality. MATERIALS AND METHODS: Patients undergoing peritoneal dialysis (PD) (n=22) and hemodialysis (HD) (n=38) and patients with pre-dialysis CKD stage IV or V (n=28) were included. AHRT activity and intracellular adenosine triphosphate (ATP) levels were measured. We performed a correlation analysis for AHRT activity, ATP levels, and various clinical parameters. RESULTS: AHRT activity and intracellular ATP levels were inversely correlated and differed according to treatment modalities. AHRT activity was higher in non-dialysis CKD patients than in patients undergoing dialysis and was higher in patients undergoing HD, compared to PD. AHRT activity decreased after HD treatment in HD patients. ATP levels were higher in healthy controls than in patients with pre-dialysis CKD and PD and were further decreased in patients with HD. We noted significant correlations between multiple clinical parameters associated with cardiovascular risk factors and AHRT activity. CONCLUSION: AHRT activity was elevated in CKD patients, while dialysis treatment reduced AHRT activity. Further studies are warranted to specify AHRT activity and to evaluate the precise roles thereof in patients with CKD.

Analysis of Syndecan-2 Methylation in Bowel Lavage Fluid for the Detection of Colorectal Neoplasm.

Background/Aims: Syndecan-2 (SDC2) methylation was previously reported as a sensitive serologic biomarker for the early detection of colorectal cancer (CRC). The purpose of this study was to investigate whether SDC2 methylation is detectable in precancerous lesions and to determine the feasibility of using SDC2 methylation for the detection of CRC and precancerous lesions in bowel lavage fluid (BLF). Methods: A total of 190 BLF samples were collected from the rectum at the beginning of colonoscopy from patients with colorectal neoplasm and healthy normal individuals. Fourteen polypectomy specimens were obtained during colonoscopy. A bisulfite pyrosequencing assay and quantitative methylation-specific polymerase chain reaction were conducted to measure SDC2 methylation in tissues and BLF DNA. Results: SDC2 methylation was positive in 100% of villous adenoma (VA) and high-grade dysplasia, and hyperplastic polyp samples; 88.9% of tubular adenoma samples; and 0% of normal mucosa samples. In the BLF DNA test for SDC2 methylation, the sensitivity for detecting CRC and VA was 80.0% and 64.7%, respectively, at a specificity of 88.9%. The BLF of patients with multiple tubular adenomas, single tubular adenoma and hyperplastic polyps showed 62.8%, 26.7% and 28.6% rates of methylation-positive SDC2, respectively. Conclusions: Our results demonstrated that SDC2 methylation was a frequent event in precancerous lesions and showed high potential in BLF for detecting patients with colorectal neoplasm.

Determination of optimized oxygen partial pressure to maximize the liver regenerative potential of the secretome obtained from adipose-derived stem cells.

BACKGROUND: A hypoxic-preconditioned secretome from stem cells reportedly promotes the functional and regenerative capacity of the liver more effectively than a control secretome. However, the optimum oxygen partial pressure (pO2) in the cell culture system that maximizes the therapeutic potential of the secretome has not yet been determined. METHODS: We first determined the cellular alterations in adipose tissue-derived stem cells (ASCs) cultured under different pO2 (21%, 10%, 5%, and 1%). Subsequently, partially hepatectomized mice were injected with the secretome of ASCs cultured under different pO2, and then sera and liver specimens were obtained for analyses. RESULTS: Of all AML12 cells cultured under different pO2, the AML12 cells cultured under 1% pO2 showed the highest mRNA expression of proliferation-associated markers (IL-6, HGF, and VEGF). In the cell proliferation assay, the AML12 cells cultured with the secretome of 1% pO2 showed the highest cell proliferation, followed by the cells cultured with the secretome of 21%, 10%, and 5% pO2, in that order. When injected into the partially hepatectomized mice, the 1% pO2 secretome most significantly increased the number of Ki67-positive cells, reduced serum levels of proinflammatory mediators (IL-6 and TNF-α), and reduced serum levels of liver transaminases. In addition, analysis of the liver specimens indicated that injection with the 1% pO2 secretome maximized the expression of the intermediate molecules of the PIP3/Akt and IL-6/STAT3 signaling pathways, all of which are known to promote liver regeneration. CONCLUSIONS: The data of this study suggest that the secretome of ASCs cultured under 1% pO2 has the highest liver reparative and regenerative potential of all the secretomes tested here.

One-pot multicomponent coupling methods for the synthesis of diastereo- and enantioenriched (Z)-trisubstituted allylic alcohols.

(Z)-trisubstituted allylic alcohols are widespread structural motifs in natural products and biologically active compounds but are difficult to directly prepare. Introduced herein is a general one-pot multicomponent coupling method for the synthesis of (Z)-alpha,alpha,beta-trisubstituted allylic alcohols. (Z)-trisubstituted vinylzinc reagents are formed in situ by initial hydroboration of 1-bromo-1-alkynes. Addition of dialkylzinc reagents induces a 1,2-metalate rearrangement that is followed by a boron-to-zinc transmetalation. The resulting vinylzinc reagents add to a variety of prochiral aldehydes to produce racemic (Z)-trisubstituted allylic alcohols. When enantioenriched aldehyde substrates are employed, (Z)-trisubstituted allylic alcohols are isolated with high dr (>20:1 in many cases). For example, vinylation of enantioenriched benzyl-protected alpha- and beta-hydroxy propanal derivatives furnished the expected anti-Felkin addition products via chelation control. Surprisingly, silyl-protected alpha-hydroxy aldehydes also afford anti-Felkin addition products. A protocol for the catalytic asymmetric addition of (Z)-trisubstituted vinylzinc reagents to prochiral aldehydes with a (-)-MIB-based catalyst has also been developed. Several additives were investigated as inhibitors of the Lewis acidic alkylzinc halide byproducts, which promote the background reaction to form the racemate. Alpha-ethyl and alpha-cyclohexyl (Z)-trisubstituted allylic alcohols can now be synthesized with excellent levels of enantioselectivity in the presence of diamine inhibitors.

New bimetallic complexes of late transition metals involving pyrazole-bridged bis N-heterocyclic carbene ligands.

Bimetallic Ni, Rh, and Ir complexes of pyrazolate biscarbene containing bulky substituents have been synthesized and characterized by X-ray crystallography; the Ni complex dimerizes to a highly congested L(2)Ni(2) structure, whereas the corresponding Rh and Ir complexes form bimetallic LM(2) structures.

Catalytic asymmetric generation of (Z)-disubstituted allylic alcohols.

A one-pot method for the direct preparation of enantioenriched (Z)-disubstituted allylic alcohols is introduced. Hydroboration of 1-halo-1-alkynes with dicyclohexylborane, reaction with t-BuLi, and transmetalation with dialkylzinc reagents generate (Z)-disubstituted vinylzinc intermediates. In situ reaction of these reagents with aldehydes in the presence of a catalyst derived from (-)-MIB generates (Z)-disubstituted allylic alcohols. It was found that the resulting allylic alcohols were racemic, most likely due to a rapid addition reaction promoted by LiX (X = Br and Cl). To suppress the LiX-promoted reaction, a series of inhibitors were screened. It was found that 20-30 mol % tetraethylethylenediamine inhibited LiCl without inhibiting the chiral zinc-based Lewis acid. In this fashion, (Z)-disubstituted allylic alcohols were obtained with up to 98% ee. The asymmetric (Z)-vinylation could be coupled with tandem diastereoselective epoxidation reactions to provide epoxy alcohols and allylic epoxy alcohols with up to three contiguous stereogenic centers, enabling the rapid construction of complex building blocks with high levels of enantio- and diastereoselectivity.

Direct, stereospecific generation of (Z)-disubstituted allylic alcohols.

A one-pot method to prepare highly functionalized (Z)-disubstituted allylic alcohols is introduced. Hydroboration of a variety of 1-bromo-1-acetylenes with dicyclohexyl borane, reaction with t-BuLi, and transmetalation to zinc generates a (Z)-disubstituted vinylzinc reagent. In situ reaction of this reagent with aldehydes generates (Z)-disubstituted allylic alcohols in high yields (81-97%). Addition to chiral protected alpha- or beta-oxygenated aldehydes proceeds with diastereoselectivities between 6:1 and 18:1. The anti-Felkin product is obtained in most cases.

A green chemistry approach to a more efficient asymmetric catalyst: solvent-free and highly concentrated alkyl additions to ketones.

There is a great demand for development of catalyst systems that are not only efficient and highly enantioselective but are also environmentally benign. Herein we report investigations into the catalytic asymmetric addition of alkyl and functionalized alkyl groups to ketones under highly concentrated and solvent-free conditions. In comparison with standard reaction conditions employing toluene and hexanes, the solvent-free and highly concentrated conditions permit reduction in catalyst loading by a factor of 2- to 40-fold. These new conditions are general and applicable to a variety of ketones and dialkylzinc reagents to provide diverse tertiary alcohols with high enantioselectivities. Using cyclic conjugated enones, we have performed a tandem asymmetric addition/diastereoselective epoxidation using the solvent-free addition conditions followed by introduction of a 5.5 M decane solution of tert-butyl hydroperoxide (TBHP) to generate epoxy alcohols. This one-pot procedure allows access to syn epoxy alcohols with three contiguous stereocenters with excellent enantio- and diastereoselectivities and high yields. Both the solvent-free asymmetric additions and asymmetric addition/diastereoselective epoxidation reactions have been conducted on larger scale (5 g substrate) with 0.5 mol % catalyst loadings. In these procedures, enantioselectivities equal to or better than 92% were obtained with isolated yields of 90%. The solvent-free and highly concentrated conditions are a significant improvement over previous solvent-based protocols. Further, this chemistry represents a rare example of a catalytic asymmetric reaction that is highly enantioselective under more environmentally friendly solvent-free conditions.

Catalytic asymmetric synthesis of hydroxy enol ethers: approach to a two-carbon homologation of aldehydes.

[reaction: see text] Hydroboration of ethoxy acetylene, transmetalation to zinc, and addition to aldehydes in the presence of a chiral amino alcohol ligand (MIB) affords hydroxy enol ethers with high ee. The resultant enantiomerically enriched hydroxy enol ethers were converted to protected hydroxy aldehydes, a useful synthetic building block for the construction of a variety of polyoxygenated natural products. In addition, diastereoselective formation of syn- and anti-1,3-diols was studied.

Catalytic asymmetric addition of alkylzinc and functionalized alkylzinc reagents to ketones.

We describe our full report of the catalytic asymmetric addition of simple and functionalized dialkylzinc reagents to a broad range of saturated ketones and enones. The functionalized organozinc reagents contain esters, silyl ethers, alkyl chlorides, and alkyl bromides. In general, the resulting tertiary alcohol products are isolated with high ee's. With some substrates, yields are low as a result of the formation of aldol byproducts. Most substrates undergo additions with good yields reaching as high as 91%.

Asymmetric addition of alkylzinc reagents to cyclic alpha,beta-unsaturated ketones and a tandem enantioselective addition/diastereoselective epoxidation with dioxygen.

Although over 100 catalysts have been reported to catalyze the asymmetric addition of alkyl groups to aldehydes, these catalysts fail to promote additions to ketones with >90% enantioselectivity. This paper describes the asymmetric 1,2-addition of alkyl groups to conjugated cyclic enones to give allylic alcohols with chiral quaternary centers. The resultant allylic alcohols are converted into epoxy alcohols with excellent diastereoselectivities. Treatment of the epoxy alcohols with BF3.OEt2 induces a semipinacol rearrangement to provide alpha,alpha-dialkyl-beta-hydroxy ketones with all-carbon chiral quaternary centers. We also report a one-pot procedure for the asymmetric addition/diastereoselective epoxidation reaction. Simply exposing the reaction mixture to dioxygen after the asymmetric addition reaction is complete results in epoxidation of the allylic alcohol with high diastereoselectivity.

Synthesis of Chiral C(2)-Symmetric Bisferrocenyldiamines. X-ray Crystal Structure of Ru(2)Cl(2).2CHCl(3) (2 = N1,N2-Bis{(R)-1-[(S)-2-(diphenylphosphino)]ferrocenylethyl}- N1,N2-dimethyl-1,2-ethanediamine).

A new class of chiral C(2)-symmetrical bisferrocenyl diamines, N1,N2-bis[(R)-1-ferrocenylethyl]-N1,N2-dimethyl-1,2-ethanediamine (1) and N1,N2-bis{(R)-1-[(S)-2-(diphenylphosphino)]ferrocenylethyl}-N1,N2-dimethyl-1,2-ethanediamine (2), were prepared from the chiral template (R)-N,N-(dimethylamino)-1-ferrocenylethylamine ((R)-FA). Compound 1 was prepared from the reaction of (R)-FA with MeI followed by nucleophilic substitution with N,N'-dimethylethylenediamine, while 2 was formed from 1 via ortho lithiation followed by electrophilic substitution with chlorodiphenylphosphine. Compound 2 reacts with Ru(DMSO)(4)Cl(2) to give trans-Ru(2)Cl(2) (3) in which the ligand is tetradentate. This complex crystallizes in the orthorhombic system: P2(1)2(1)2(1) (No. 19); a = 11.7230(4) Å, b = 16.5951(6) Å, c = 27.853(1) Å; Z = 4; R = 0.046; R(w) = 0.104. The geometry around the central metal is an octahedron with a pair of chlorine atoms trans to each other. This complex exhibits catalytic activity toward asymmetric cyclopropanation of some olefins and alkyl diazoacetates, giving enantioselectivity up to 95%.