Determination of the absolute configurations of 4-mercapto-2-alkanones using the <Superscript>1</Superscript>H NMR anisotropy method and enzyme-catalyzed kinetic resolution of the corresponding 4-acetylthio-2-alkanones

To determine the capillary gas chromatographic (GC) elution order of the enantiomers of 4-mercapto-2-alkanones, racemic 4-acetylthio-2-alkanones were synthesized and hydrolyzed by lipases to get enantio-enriched 4-mercapto-2-alkanones that were resolved by capillary gas chromatography using a chiral stationary phase. The obtained enantio-enriched 4-mercapto-2-alkanones were esterified with (S)-2-methoxy-2-(1-naphthyl)propionic acid ((S)-MαNP acid), and the HPLC analysis of MαNP thioesters revealed the same isomeric ratios as the chiral GC analysis of the corresponding thiol enantiomers. The diastereoisomeric thioesters obtained were resolved by HPLC, and the absolute configurations were determined on the basis of ¹H NMR anisotropy effects. On the basis of these results, the GC elution order of the enantiomers of 4-mercapto-2-alkanones and of the corresponding 4-acetylthio-2-alkanones could be determined. The combination of enzymatic resolution and MαNP thioesterification proved to be a useful tool to determine the absolute configuration of secondary thiols.     

Examination of the role of oxygen in the photografting of methacrylic acid on a polyethylene film with a mixed solvent consisting of water and organic solvents

The photografting of methacrylic acid (MAA) on a linear low‐density polyethylene film (thickness = 30 μm) under air and nitrogen atmospheres was investigated at 60°C in mixed solvents consisting of water and an organic solvent, with xanthone as a photoinitiator. The organic solvents used were acetone, methanol, tetrahydrofuran, and dioxane. A maximum percentage of grafting occurred at a certain concentration of the organic solvent in the mixed solvent. This was observed for the systems under both air and nitrogen. The grafting reaction under air exhibited an induction period, but the rate of grafting after the period was greater than that under nitrogen. The formation of poly(ethylene peroxide)s by photoirradiation seemed to be a factor for the accelerated photografting under air. On the basis of attenuated total reflection infrared spectroscopy and scanning electron microscopy of the grafted film, the MAA‐grafted chains of the sample prepared under air tended to penetrate more deeply inside the film than those of the sample prepared under nitrogen. The resulting grafted films exhibited a pH‐responsive character: the grafted films shrank in an acidic medium but swelled in alkaline medium. This was evaluated from measurements of dimensional changes in the grafted films. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 992–998, 2003     

Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats

Metabolic syndrome is associated with an increased risk of colorectal cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Lepr^fa/IzmDmcr (SHRSP-ZF) diabetic/hypertensive rats. Male 6-week-old SHRSP, SHRSP-ZF, and control non-diabetic/normotensive Wister Kyoto/Izm (WKY) rats were given 2 weekly intraperitoneal injections of AOM (20 mg/kg body weight). Two weeks after the last injection of AOM, the SHRSP and SHRSP-ZF rats became hypertensive compared to the control WKY rats. Serum levels of angiotensin-II, the active product of the renin-angiotensin system, were elevated in both SHRSP and SHRSP-ZF rats, but only the SHRSP-ZF rats developed insulin resistance, dyslipidemia, and hyperleptinemia and exhibited an increase in adipose tissue. The development of AOM-induced colonic preneoplastic lesions and aberrant crypts foci, was significantly accelerated in both SHRSP and SHRSP-ZF hypertensive rats, compared to WKY normotensive rats. Furthermore, induction of oxidative stress and exacerbation of inflammation were observed in the colonic mucosa and systemically in SHRSP and SHRSP-ZF rats. Our findings suggest that hypertension plays a role in the early stage of colorectal carcinogenesis by inducing oxidative stress and chronic inflammation, which might be associated with activation of the renin-angiotensin system.     

Novel Fabrication of High-Quality ZrO2 Ceramic Thin Films from Aqueous Solution

We report on the direct deposition of high-quality ZrO₂ thin films on various kinds of substrates by the liquid phase deposition method. After reaction for 24 h, thin films formed on various kinds of substrates, and the obtained thin film was comprised of densely packed nano-sized particles. The film annealed at 500°C showed a tetragonal phase at room temperature and this phenomenon has been discussed from the viewpoint of crystallite size effect. The result of optical transmittance measurement revealed that high transparency, more than 70% transmittance, has been achieved for the film after annealing at 900°C.     

Picoliter volume glass tube array fabricated by Si electrochemical etching process

Fabrication process for picoliter volume SiO₂ glass tube array partially embedded in Si wafer was developed. As a template for the glass tubes, macropore array was formed at the surface of n-Si(1 0 0) wafer by photo-assisted electrochemical etching process. The area-selective formation of the array was achieved by applying Au/Cr micropatterns formed at the back-side surface of the substrate as the shade mask, which controls the illumination condition to optimize the etching reaction conditions. Subsequently, surface of the macropores was wet-thermally oxidized to form glass layer, and the bulk Si region was removed by alkaline etching, remaining the “glass tubes”. As a result of complete removal of the bulk Si, released glass tubes were obtained. By partial removal of the bulk Si part, the glass tubes were exposed, fixed in the remaining Si substrate in the form of well-ordered array. It was confirmed that the depth, the exposed region and the wall thickness of each glass tube were controllable by adjusting the parameters such as the duration of the Si electrochemical etching, the alkaline etching and the wet-thermal oxidation, respectively. In order to demonstrate microreaction in the glass tube, aqueous rhodamine B solution was injected into the tubes and excitation light was irradiated to them. As a result, the fluorescence of rhodamine B was clearly detected, confirming the applicability of the glass tubes for various kinds of devices and systems such as microreactors.     

Cerebral Hyperperfusion after Revascularization Inhibits Development of Cerebral Ischemic Lesions Due to Artery-to-Artery Emboli during Carotid Exposure in Endarterectomy for Patients with Preoperative Cerebral Hemodynamic Insufficiency: Revisiting the “Impaired Clearance of Emboli” Concept

The purpose of the present study was to determine whether cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during exposure of the carotid arteries in carotid endarterectomy (CEA). In patients undergoing CEA for internal carotid artery stenosis (≥70%), cerebral blood flow (CBF) was measured using single-photon emission computed tomography (SPECT) before and immediately after CEA. Microembolic signals (MES) were identified using transcranial Doppler during carotid exposure. Diffusion-weighted magnetic resonance imaging (DWI) was performed within 24 h after surgery. Of 32 patients with a combination of reduced cerebrovascular reactivity to acetazolamide on preoperative brain perfusion SPECT and MES during carotid exposure, 14 (44%) showed cerebral hyperperfusion (defined as postoperative CBF increase ≥100% compared with preoperative values), and 16 (50%) developed DWI-characterized postoperative cerebral ischemic lesions. Postoperative cerebral hyperperfusion was significantly associated with the absence of DWI-characterized postoperative cerebral ischemic lesions (95% confidence interval, 0.001–0.179; p = 0.0009). These data suggest that cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during carotid exposure in CEA, supporting the “impaired clearance of emboli” concept. Blood pressure elevation following carotid declamping would be effective when embolism not accompanied by cerebral hyperperfusion occurs during CEA.     

C57BL/KsJ-db/db-Apc Mice Exhibit an Increased Incidence of Intestinal Neoplasms

The numbers of obese people and diabetic patients are ever increasing. Obesity and diabetes are high-risk conditions for chronic diseases, including certain types of cancer, such as colorectal cancer (CRC). The aim of this study was to develop a novel animal model in order to clarify the pathobiology of CRC development in obese and diabetic patients. We developed an animal model of obesity and colorectal cancer by breeding the C57BL/KsJ-db/db (db/db) mouse, an animal model of obesity and type II diabetes, and the C57BL/6J-Apc(Min/+) (Min/+) mouse, a model of familial adenomatous polyposis. At 15 weeks of age, the N9 backcross generation of C57BL/KsJ-db/db-Apc(Min/+) (db/db-Min/+) mice developed an increased incidence and multiplicity of adenomas in the intestinal tract when compared to the db/m-Min/+ and m/m-Min/+ mice. Blood biochemical profile showed significant increases in insulin (8.3-fold to 11.7-fold), cholesterol (1.2-fold to 1.7-fold), and triglyceride (1.2-fold to 1.3-fold) in the db/db-Min/+ mice, when compared to those of the db/m-Min/+ and m/m-Min/+ mice. Increases (1.4-fold to 2.6-fold) in RNA levels of insulin-like growth factor (IGF)-1, IRF-1R, and IGF-2 were also observed in the db/db- Min/+ mice. These results suggested that the IGFs, as well as hyperlipidemia and hyperinsulinemia, promoted adenoma formation in the db/db-Min/+ mice. Our results thus suggested that the db/db-Min/+ mice should be invaluable for studies on the pathogenesis of CRC in obese and diabetes patients and the therapy and prevention of CRC in these patients.     

Nile blue adsorbed onto silica gel modified with niobium oxide for electrocatalytic oxidation of NADH

A study of modified carbon paste electrode employing Nile blue (NB) adsorbed on silica gel modified with niobium oxide (SN) for electrocatalytic oxidation of reduced nicotinamide adenine dinucleotide (NADH) is described. The adsorbed organic dye on SN was used to prepare a modified carbon paste electrode to investigate its electrochemical properties. The formal potential (E°′) of the adsorbed NB (−230 mV vs. saturated calomel electrode, SCE) showed a shift of 70 mV towards a more positive potential value, compared to NB dissolved in aqueous solution. In solutions with pH between 6.0 and 8.0 did stability and E°′ remained almost constant. However, for a solution pH lower than 6.0 the E°′ was affected by the acidity of the contacting solution, shifting the E°′ towards more positive values. For the solution pHs between 6.0 and 8.0 the electrocatalytic activity remained almost constant. A linear response range for NADH between 1.0×10⁻⁵ and 5.2×10⁻⁴ mol l⁻¹, at pH 7.0, was observed for the electrode, with an applied potential of −200 mV versus SCE. The formation of an intermediate charge transfer (CT) complex was proposed to the CT reaction between NADH and adsorbed NB. The heterogeneous electron transfer rate, k_obs, was 1400 M⁻¹ s⁻¹ and the apparent Michaelis-Menten constant, was 0.21 mM at pH 7.0 evaluated from rotating disk electrode (RDE) experiments with an electrode coverage of about 5.2×10⁻⁹ mol cm⁻². The increase in the reaction rate between NADH and the immobilized NB compared to those obtained with dissolved NB was assigned to the shift of the E°′ towards more positive values.