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We aim to elucidate the chemical damage structure in poly(allyl diglycol carbonate), PADC, exposed to UV photons with a wavelength of 222 nm using FT-IR spectrometric method. The number density of carbonyl (C˭O) in PADC, which composes carbonate ester, is hardly affected by the UV photons below the critical fluence of 3.0 × 1019 photons/cm2. The number density of carbonyl decreases only above the critical fluence, while those of ether and C-O-C in carbonate ester are monotonically cleaved. These findings corroborate the previous result using 28 MeV electron beams, in which the carbonate ester is lost only above the critical fluence of 1.6 × 1015 electrons/cm2, where the overlapping of electron tracks becomes significant. We extend the conventional track overlapping model to clarify the spatial distribution of point-like defects after the UV exposure. The discrete damage is seen at the critical condition, based on the extended track overlapping model.

Objective: SGLT2 inhibitors (SGLT2i) were examined for their effects on nighttime sympathetic nerve activity in type 2 diabetic patients. Methods: A total of 15 type 2 diabetic outpatients with poor glycemic and body weight control despite conventional antidiabetic therapy (HbA1c, 7.7 ± 1.1%; BMI, 27.6 ± 3.8 kg/m2) were given dapagliflozin (Dapa) 5 mg/day for 3 months. Patients were compared before and 3 months after Dapa treatment for Low frequency/High frequency (LF/HF) ratios at 5-minute intervals as index of sympathetic verve activity through spectrum analysis of heart rate variability, blood pressure (BP) variability at 30-minute intervals, glucose variability at 5-minute intervals using concurrent Holter electrocardiogram, ambulatory blood pressure monitoring, and continuous glucose monitoring. Blood samples were drawn from these patients after 30 minutes of bed rest before and 3 months after Dapa treatment to measure their plasma catecholamine values. Outcome measures of the study included the area under the curve for LF/HF ratios (AUC-LF/HF ratio), mean BP values during sleep, extent of nighttime BP dip, and mean glucose/SD of glucose values during sleep. Results: HbA1c and body weight were significantly decreased with Dapa. Again, the nighttime AUC-LF/HF ratio and plasma noradrenalin values, as well as the heart rate, systolic BP (SBP) and diastolic BP (DBP) values during the same hours, were significantly decreased, and the extent of nighttime BP dip was also significantly increased, in those achieving weight reductions with Dapa. In contrast, these findings were not observed in 3 patients failing to achieve weight reductions with Dapa. Conclusions: Study results suggest that reductions in sympathetic nerve activity associated with the SGLT2i treatment may be closely associated with SGLT2i-mediated weight reductions. Disclosure T. Onishi: None. Y. Shioda: None. Y. Mori: None.

International audience; The detection threshold of poly(allyl dyglycol carbonate), PADC, for C ions is determined as 55 eV/nm in stopping power, which is significantly higher than that for proton and He ions. The stopping power is not a universal parameter for expressing the detection threshold of PADC. A new physical parameter of Radial Electron Fluence around Ion Tracks, REFIT, is proposed to describe the detection threshold of PADC. It is defined as the number density of electrons passing through the surface of a cylinder of a certain radius that is co-axial with the trajectory. Furthermore, preliminary calculations are presently being performed using the Monte Carlo simulation code of Geant4-DNA. The values of the REFIT at the detection thresholds for each ion are of the same order. Several issues affecting implementation of the REFIT paramter are discussed. These include the effects of impact parameter relating to the initial locations of secondary electrons, the effects of electron attachment below the cut off energy of 7.4 eV and the necessity of a more physically realistic medium than water for Monte Carlo simultaions.

G values of the losses of typical functional groups in PET films along boron ion tracks have been determined using FT-IR spectrometry. G value for the loss of aromatic-ring clearly increases above 270 eV/nm. Those of ester and ethylene increase around the slightly lower stopping power of 250 eV/nm. The detection thresholds are defined by determining the original points from which the evolution of etch pit starts along the latent track, when the chemical etching was progressing starting from the front surface of each incident ion trajectory. The thresholds for B, C, N, O, Ar and Kr ions have been determined for other kind of PET sheets. Values of the sensitivity at the thresholds are fairly higher at heavy ions with smaller atomic number.

Objective: We investigated the relationship between enhanced efficacy of incretin-related drugs with add-on SGLT2 inhibitor therapy in type 2 diabetic patients and their background characteristics. Patients and Methods: 1) Add-on SGLT2i therapy was given to a total of 15 type 2 diabetic patients with insufficient glycemic control despite conventional therapy including DPP-4i for 2 months in an outpatient setting. 2) Likewise, add-on SGLT2i therapy was given to a total of 17 type 2 diabetic patients with insufficient glycemic control despite conventional therapy including GLP-1RA for 3 months in an outpatient setting. In both groups, the glycemic variability (GV) was compared before and after add-on SGLT2i therapy by using CGM. GV indices evaluated included the difference before and after SGLT2i therapy in SD of 24-hour glucose values (ΔSD), the 24-hour total GV area (ΔSQ), and MAGE (ΔMAGE). Both groups were further divided according to the GV results by over 50th %tile and under 50th %tile into high-responders (n = 8 and 9) and low-responders (n = 7 and 8). Results: 1) Effect of add-on SGLT2i therapy on reductions in GV in those receiving DPP-4i: High-responders were shown to be associated with significantly higher mean glucose values, SD, SQ and MAGE than low-responders at baseline (P < 0.05). 2) Effect of add-on SGLT2i therapy on reductions in GV in those receiving GLP-1RA: high-responders were shown to be associated with significantly lower BMI, as well as significantly higher SD and SQ than low-responders at baseline (P < 0.05). Conclusions: With 2-month SGLT2i therapy as add-on to DPP-4i, reductions were seen in GV among patients with higher mean glucose and greater GV at baseline, suggesting a role for add-on SGLT2i therapy particularly in those with poor glycemic control. In contrast, with 3-month SGLT2i therapy as add-on to GLP-1RA, reductions were seen in GV among those with less severe obesity and greater GV at baseline. Disclosure T. Onishi: None. Y. Shioda: None. Y. Mori: None.

We propose an adaptive point-spread spherical wave synthesis method based on the point-source hologram technique for fast hologram pattern generation. The calculation time of the hologram generation is reduced by decreasing the number of reconstructed point sources composing an object. A larger point source is reconstructed in the area where an object can be partially expressed by low resolution. The point-spread is adjusted corresponding to the spatial frequency of an object. The effectiveness of the proposed method is confirmed by a computer simulation using two-dimensional images.

A series of FT-IR spectrometric studies has been performed to understand the latent track structure in poly(allyl diglycol carbonate), PADC, which were exposed to proton beams with energies of 20, 30 and 70 MeV. These energies are too high to register etchable tracks in PADC. Chemical damage parameters, such as damage density, effective track core radius and radiation chemical yields, for losses of ether bond, carbonate ester bond and CH groups in PADC are evaluated as a function of the stopping power, which were compared to the previous results for 5.7 MeV proton and heavy ions, between He and Xe. Graphs of the chemical damage parameters are given at the wide stopping powers ranging from 1 to 12,000 keV/μm. The decreasing behaviors of the ether and carbonate ester bonds are on the almost identical trends with those of the heavy ions. On the contrary to this, the reducing behavior of CH groups is similar to that of the gamma rays. Different dependence of the chemical damage parameters for the loss of CH groups is found on the stopping powers between the both sides of the detection threshold as an etched track detector.

Modified structure along ion tracks in poly(allyl diglycol carbonate), PADC, films exposed to protons and heavy ions, He, C, Ne, Ar, Fe, and Xe, in air has been examined by means of FT-IR spectroscopy, covering the stopping power ranging from 10 to 12,000 keV/μm. The damage density for the loss of CH groups and the amount of formed OH groups along each tracks are estimated and compared to the previous results on the ether and the carbonate ester bonds. The CH groups are lost in the center region of the track core with other functional groups and the OH groups are created as new end-points of the polymer network. We obtained the molar absorption coefficient for OH of water absorbed in PADC films as 9.7 × 103 M−1 cm−1. It has been assumed that the coefficient is applicable to the OH groups on the polymer. The amount of OH groups are almost equivalent to the damage density of the ether bonds.

A first attempt is made to mix the radial dose model with a simple radio-oxidation kinetic to simulate the G values for carbonate ester bond scissions in PADC induced by different ions from proton to Xenon with LET ranging from 10 to 1.20 × 10 4 keV μm −1 . Even if some discrepancies exist between experimental and simulated data, this work tends to prove that O 2 concentration in PADC rules the observed experimental LET dependence on carbonate ester bond scission in PADC irradiated in air.

A speckle reduction method based on a spherical waves synthesis with low-coherence digital holography for hologram generation is proposed. An object information is experimentally obtained from a number of recorded low-coherence digital holograms. A hologram is generated by synthesizing the fields of spherical waves with the obtained information. The performance of the proposed method as hologram generation from a distribution contained spike noises like speckles is confirmed. The image quality is evaluated by the speckle contrast of the reconstructed image.

A low-carbohydrate/high-monounsaturated fatty acid liquid diet (LC/HMD) was investigated for its role in long-term glycemic control in tube-fed type 2 diabetes patients who require insulin therapy.The study included 10 type 2 diabetes patients requiring insulin therapy who were being tube-fed with a high-carbohydrate liquid diet (HCD). With stable glucose control maintained, these patients were monitored for glucose levels for 4 consecutive days by using continuous glucose monitoring (CGM). The patients were continued on HCD during the first 2 days and were switched to an LC/HMD during the final 2 days. The patients were then continued on the LC/HMD, and seven of the 10 patients were monitored for glucose levels for 2 consecutive days by using CGM after 3 months of feeding with the LC/HMD. Insulin regimens used included basal-bolus insulin in five of these seven patients and intermediate-acting insulin in two patients.Based on CGM data, the indices for glucose variability, such as SDs of 288 glucose levels for 24 h, total area for the range of glucose variability, mean amplitude of glycemic excursions, and 24-h mean glucose levels were significantly decreased 3 months after switching from the HCD to the LC/HMD. Additionally, despite the significant decrease in required insulin dose, the hemoglobin A1c (HbA1c) values were significantly decreased 3 months after switching.Study results demonstrated that the LC/HMD not only narrowed the range of glucose variability, but also decreased the required insulin dose and HbA1c values in diabetes patients on tube feeding who required insulin therapy, suggesting the LC/HMD may be useful in long-term glycemic control in these patients.

In an attempt to utilize felled palm trunks, we found that they contain a large quantity of sap, and that abundant glucose and other fermentable sugars exist in the sap. In this study, we developed a prototype system for compressing the sap from oil palm trunks; it is composed of a rotary lathe, a shredder, and a compressing mill. A high compression efficiency of the mill was maintained (a sap recovery of ∼80%) by properly preparing the trunks, which included peeling the bark and the outer layer of the trunks. In addition, a higher compression efficiency was obtained with a relatively slow rotation of the mill. Consequently, the net energy ratio (NER) reached 4.8 when the sugar concentration in the sap was 79 kg m −3 . This is the first paper about new developed systems for sap compressed from oil palm trunk.

Cassava pulp containing 60% starch and 20% cellulose is a promising renewable source for bioethanol. The starch granule was observed to tightly bind cellulose fiber. To achieve an efficient degradation for cassava pulp, saccharification tests without pre-gelatinization treatment were carried out using combination of commercial α-amylase with cellulosome from Clostridium thermocellum S14 and β-glucosidase (rCglT) from Thermoanaerobacter brockii. The saccharification rate for cassava pulp was shown 59% of dry matter. To obtain maximum saccharification rate, glucoamylase (GA) from C. thermocellum S14 was supplemented to the combination. The result showed gradual increase in the saccharification rate to 74% (dry matter). Supplementation of GA to the combination of commercial α-amylase, cellulosome and rCglT is powerful method for efficient saccharification of cassava pulp without pretreatment.

In order to understand the vacuum effects on the sensitivity of PADC detectors from the viewpoint of molecule structural modification along nuclear tracks, a series of FT-IR spectrometric studies has been made for PADC films exposed to He and C ions at energies below 6 MeV/n, as well as to gamma rays from an intense Co-60 source, under the both conditions of in air and in vacuum. The radiation chemical yields for the losses of ether and carbonate ester bonds are hardly affected by the environmental conditions in the cases of He and C ion irradiations. For gamma ray, the yields are about half in vacuum compared to those in air. The formation of OH groups is fairly suppressed in vacuum in all cases. Recombination of free radicals resulted in modified polymeric network formation would be enhanced in heavy ion irradiations rather than in that of gamma irradiations.

Chemical ester bond scission induced by incoming ions in polyethylene terephthalate (PET), bisphenol A polycarbonate (PC), polyallyl diglycol carbonate (PADC), have been systematically determined by FT-IR transmission measurements. The studied ions (H, He, C, Ne, I, Ar, Fe, Kr, Xe) have LET ranging from 10 to 10 000 keV μm −1 . We discuss the opportunity to simulate the experimental chemical cross section obtained with an approach based on the dose deposited by the secondary electrons removed by the incoming ion. Such an approach has been already successfully applied for LR115.

Track registration properties in polyimide films, KAPTON, for heavy ions have been examined by means of FT-IR spectrometry and the chemical etching in sodium hypochlorite solution. The effective track core size for the loss of C O and C–N–C composing imide bonds, and diphenyl ethers of C–O–C have been evaluated under the irradiations by Ne, Fe and Xe ions at energies less than 6 MeV/n. On the other hand, the etching property of the polyimide films has been examined in the sodium hypochlorite solution at temperature of 55 °C. Before the etchings, the films were exposed to H, C, Ne, Fe and Xe ions, at incident energies below 6 MeV/n. The etch pits are found only on the films exposed to Fe and Xe ions, indicating significant difference on the etch pit size between them. This implies that the polyimide film has charge or energy resolution for these relatively heavy ions. The threshold level of the etchable track registration is inferred to be around 2500 keV/μm. The effective track core radius at this stopping power for the loss of diphenyl ether is 1.6 nm, which is equivalent to the length between the adjacent diphenyl ether bonds in the polyimide chains. Breakings at two adjacent diphenyl ethers in radial direction of latent tracks may produce etchable tracks in KAPTON.

For efficient utilization of both starchy and cellulosic materials, oil palm trunk was separated into parenchyma (PA) and vascular bundle (VB). High solid-state simultaneous saccharification and fermentation (HSS-SSF) using 30% (w/v) PA, containing 46.7% (w/w) starch, supplemented with amylases and Saccharomyces cerevisiae K3, produced 6.1% (w/v) ethanol. Subsequent alkali-pretreatment using sodium hydroxide was carried out with starch-free PA (sfPA) and VB. Enzymatic digestibility of 5% (w/v) pretreated sfPA and VB was 92% and 97%, respectively, using 18 FPU of commercial cellulase supplemented with 10 U of Novozyme-188 per gram of substrate. Likewise, HSS-SSF using 30% (w/v) alkali-pretreated sfPA and VB, with cellulases and yeast, resulted in high ethanol production (8.2% and 8.5% (w/v), respectively). These results show that HSS-SSF using separated PA and VB is a useful fermentation strategy, without loss of starchy and cellulosic materials, for oil palm trunk.

As a feasibility study, gas chromatography–mass spectrometry (GC–MS) and matrix-assisted laser desorption ionization–mass spectrometry (MALDI–MS) have been applied to analyze etch products of CR-39 plastic (one of the most frequently used solid states nuclear track detector) for the understanding of track formation and etching mechanisms by heavy ion irradiation. The etch products of irradiated CR-39 dissolved in sodium hydroxide solution (NaOH) contain radiation-induced fragments. For the GC–MS analysis, we found peaks of diethylene glycol (DEG) and a small but a definitive peak of ethylene glycol (EG) in the etch products from CR-39 irradiated by 60 MeV N ion beams. The etch products of unirradiated CR-39 showed a clear peak of DEG, but no other significant peaks were found. DEG is known to be released from the CR-39 molecule as a fragment by alkaline hydrolysis reaction of the polymer. We postulate that EG was formed as a result of the breaking of the ether bond (C–O–C) of the DEG part of the CR-39 polymer by the irradiation. The mass distribution of polyallylalcohol was obtained from the etch products from irradiated and unirradiated CR-39 samples by MALDI–MS analysis. Polyallylalcohol, with the repeating mass interval of m/z = 58 Da (dalton) between m/z = 800 and 3500, was expected to be produced from CR-39 by alkaline hydrolysis. We used IAA as a matrix to assist the ionization of organic analyte in MALDI–MS analysis and found that peaks from IAA covered mass spectrum in the lower m/z region making difficult to identify CR-39 fragment peaks which were also be seen in the same region. The mass spectrometry analysis using GC–MS and MALDI–MS will be powerful tools to investigate the radiation-induced polymeric fragments and helping to understand the track formation mechanism in CR-39 by heavy ions.

Clostridium thermocellum is known to produce the cellulosomes with efficient plant cell wall degradation ability. To bring out the maximum cellulolytic ability of the cellulosomes, it is necessary to eliminate the end product inhibition by cellobiose. Combinations of β-glucosidases from thermophilic anaerobic bacteria and Aspergillus niger and C. thermocellum S14 cellulosomes were evaluated for optimization of cellulose degradation. β-Glucosidase (CglT) from Thermoanaerobacter brockii, in combination with cellulosomes, exhibited remarkable saccharification ability for microcrystalline cellulose. When rice straw, soaked in 28% aqueous ammonia for 7 days at 60 °C, was hydrolyzed by an enzyme loading combination of 2 mg cellulosome and 10 units CglT per g glucan, 91% of glucan was hydrolyzed to glucose, indicating roughly1/10 the enzyme load of a Trichoderma reesei cellulase (Celluclast 1.5L) and Novozyme-188 combination is enough for the combination of C. thermocellum S14 cellulosomes and CglT to achieve the same level of saccharification of rice straw.

Chemical modification along ion tracks in PADC films has been studied by means of FT-IR spectrometry, which was exposed to proton and heavy ions of He, C, Ne, Ar, Fe, Kr and Xe with energies around the Bragg peaks. This study covers a wide region of the stopping power ranging from 10 to 10,000 keV/μm. Removal cross sections for the loss of ether and carbonate ester bonds are assessed for each ion, as a function of the stopping power. Chemical damage parameters like the damage density, the effective track core radius and the radiation chemical yields, G values (scissions/100 eV), for each bond are also derived. We have found anomalous dependence of these parameters on the stopping power. The G value for the loss of carbonate ester bond decreased from 20 for proton down to 5 for C and Ne ions, and then increased with atomic number of heavy ions up to 8 for Xe ion. Radial dose distribution for each ion has been also calculated. Results are discussed from the viewpoint of polymeric structure of PADC that consists of two parts with different radio-sensitivities.

The number of patients with both hypertension and obesity has been increasing in Japan. Many of these patients may also have insulin resistance. Telmisartan, an angiotensin II receptor blocker (ARB), selectively activates peroxisome proliferatoractivated receptor (PPAR)-gamma, and this effect is considered to markedly improve insulin resistance in obese patients with hypertension. We compared the antihypertensive and insulin resistance-improving effects of telmisartan with those of candesartan and valsartan in this patient population. Twenty-eight elderly patients with an average body mass index (BMI) of 27.1 kg/m2 were enrolled in this 6-month study. Patients were randomly selected to either switch from candesartan or valsartan to telmisartan or to continue with their current ARB. A 75 g oral glucose tolerance test (OGTT) was performed before and after switching, and the effect of telmisartan on the insulin response to glucose loading was investigated. There was no significant difference in blood pressure between the two groups after drug administration, but glucose tolerance significantly improved in the telmisartan group. The hyperinsulin response to glucose loading also significantly improved in those taking telmisartan, as well as homeostasis model assessment of insulin resistance (HOMA-IR). These changes were not observed in the control group. In patients with hypertension and obesity showing insulin resistance, treatment with telmisartan significantly improved the hyperinsulin response to glucose loading. Telmisartan may therefore be beneficial in these patients.

Angiotensin II type 1 receptor (AT1 receptor) blockers (ARBs) are one of the most popular anti-hypertensive agents. Control of blood pressure (BP) by ARBs is now a therapeutic target for the organ protection in patients with hypertension. Recent meta-analysis demonstrated the possibility that telmisartan was the strongest ARB for the reduction of BP in patients with essential hypertension. However, which molecular interactions of telmisartan with the AT1 receptor could explain its strongest BP lowering activity remains unclear. To address the issue, we constructed models for the interaction between commonly used ARBs and AT1 receptor and compared the docking model of telmisartan with that of other ARBs. Telmisartan has a unique binding mode to the AT1 receptor due to its distal benzimidazole portion. This unique portion could explain the highest molecular lipophilicity, the greatest volume distribution and the strongest binding affinity of telmisartan to AT1 receptor. Furthermore, telmisartan was found to firmly bind to the AT1 receptor through the unique "delta lock" structure. Our present study suggests that due to its "delta lock" structure, telmisartan may be superior to other ARBs in halting cardiovascular disease in patients with hypertension.

Oil palm trees are replanted at an interval of approximately 25 years because of decreased oil productivity of old trees. Consequently the felled trunks are the enormous amount of biomass resources in the palm oil producing countries such as Malaysia and Indonesia. In this report, we found that the felled oil palm trunk contains large quantity of sap, which accounts for approximately 70% of the whole trunk weight, and that sugars existing in the sap increased remarkably during storage after logging. Total sugar in the sap increased from 83 mg ml−1 to 153 mg ml−1, the concentration comparable to that of sugar cane juice, after 30 days of storage, followed by the gradual decrease. The sugars contained in the sap were glucose, sucrose, fructose and galactose, all of which are fermentable by ordinary industrial yeast strains. The results indicate that old oil palm trunk becomes a promising source of sugars by proper aging after logging and, thus, its sap can be a good feedstock for bioethanol.

Cassava ( Manihot esculenta Crantz) pulp, produced in large amounts as a by-product of starch manufacturing, is a major biomass resource in Southeast Asian countries. It contains abundant starch (approximately 60%) and cellulose fiber (approximately 20%). To effectively utilize the cassava pulp, an attempt was made to convert its components to ethanol using a sake-brewing yeast displaying glucoamylase on the cell surface. Saccharomyces cerevisiae Kyokai no. 7 (strain K7) displaying Rhizopus oryzae glucoamylase, designated strain K7G, was constructed using the C-terminal-half region of α-agglutinin. A sample of cassava pulp was pretreated with a hydrothermal reaction (140 °C for 1 h), followed by treatment with a Trichoderma reesei cellulase to hydrolyze the cellulose in the sample. The K7G strain fermented starch and glucose in pretreated samples without addition of amylolytic enzymes, and produced ethanol in 91% and 80% of theoretical yield from 5% and 10% cassava pulp, respectively.

The fading of carbon dioxide treatment on PADC detectors after alpha-particle irradiations has been confirmed to relate to the diffusion loss of carbon dioxide. Diffusion coefficient of carbon dioxide in the film is found to be D = 1.1 × 10 −9 cm 2 /s at room temperature. The effect of the post-irradiation treatment has strong relation with the dissolving process of carbon dioxide into the etching solution through the renewing surface of the detector during etching. Absorbed carbon dioxide can modify the network structure of PADC with higher permeability for etching solution.

This study examined production of α-glucosidase inhibitors by Bacillus subtilis B2 in Luria-Bertani (LB) fermentation with okara, soy powder, starch or pectin as additional source of carbon and nitrogen. All the fermentation broths of B. subtilis B2 exhibited gradual increase in α-glucosidase inhibitory activity during the fermentation process with or without supplemented source of carbon or nitrogen. Addition of okara into the LB medium greatly enhanced the strength (nearly twice as much of that without okara supplement) of α-glucosidase inhibitory activity of fermentation broth. The α-glucosidase inhibitory activity of B. subtilis B2 fermentation broth was positively correlated (p0.05) with the bacterial populations grown in LB medium containing okara. Glucose and sucrose were not detected in LB medium during the entire fermentation process and were both reduced drastically in media containing okara, soy powder, starch or pectin after 6days of fermentation. The fermented LB medium containing okara by B. subtilis B2 possessed very strong α-glucosidase inhibitory activity and contained little glucose and sucrose, suggesting that fermentation of B. subtilis B2 in LB added with okara might be considered as a strategy for preparing functional foods for diabetic patients.

The crystal structure and solid-state photoreaction of sorbamides and 2,4-hexadienyl carbamates with various N-substituents have been investigated. One-dimensional (1D) hydrogen bond chains with a repeating distance of 5 A were observed in their crystals, due to the strong intermolecular interaction between the CO and N−H groups in the amide and carbamate moieties. We have revealed that N-benzylsorbamide and 2,4-hexadienyl N-(1-naphthyl)carbamate have a molecular stacking structure appropriate for the occurring [2+2] photodimerization and topochemical polymerization, respectively. The former sorbamide derivative gave a cyclodimer with an asymmetric structure, which was determined by NMR spectroscopy, under UV irradiation in the crystalline state. The γ-radiation of the latter carbamate derivative gave a polymer that is insoluble in any solvent. The polymer structure was determined by powder X-ray diffraction and IR spectroscopy. The reactivity in the solid-state photoreaction was discussed on the basis of...

We report the polymerization mechanism and kinetics of muconic esters as the 1,3-diene monomers during solid-state polymerization via a crystal-to-crystal transformation. We have revealed a change in the structure of the muconate crystals accompanying the shrinking and expanding of the lattice lengths, on the basis of the X-ray single-crystal structure analysis of the monomers and polymers as well as a change in the transient structure monitored by powder X-ray diffraction during the continuous X-ray radiation. The polymerization rate is closely related to the molecular stacking distance in the monomer crystals because the polymer chain skeletons have the same conformational structure in the crystals. A lattice length in the direction along which a polymer chain is produced decreases during the transformation from monomer to polymer crystals when monomer molecules are arranged in a columnar assembly with a stacking distance greater than the fiber period of the resulting polymer, and vice versa. A strain i...

The solid-state photoreactions of fluorine-substituted benzyl (Z,Z)- and (E,E)-muconates have been investigated. The reaction of 16 derivatives was carried out under UV- and γ-ray radiations, and t...

Angiotensin II receptor blockers as a class are reported to act as insulin sensitizers. Of these, telmisartan has been shown to have additional unique peroxisome proliferator-activated receptor-gamma-mediated, insulin-sensitizing properties. In this study, investigators explored the effects of telmisartan on glycemic control and lipid metabolism in hypertensive patients with type 2 diabetes who had switched to telmisartan from another angiotensin II receptor blocker. The study subjects were 42 hypertensive outpatients with type 2 diabetes who were being treated with candesartan 8 mg/d and who agreed to switch to treatment with telmisartan 40 mg/d. Relevant laboratory variables were measured 6 mo before treatment switching, at the time of switching, and 6 mo after switching. No significant differences were noted in blood pressure, body mass index, or glycosylated hemoglobin among subjects before and after therapy was switched. No adverse reactions such as edema or hepatic toxicity were noted. No significant changes in fasting plasma glucose, fasting insulin, HOMA-R (insulin resistance as measured by the homeostasis model), preheparin lipoprotein lipase mass, high-density lipoprotein cholesterol, and free fatty acids were noted. Triglyceride levels were significantly decreased, however, and adiponectin levels were significantly increased (8.1+/-3.1 microg/mL at switching; 8.6+/-3.0 microg/mL 6 mo after switching; P.01) after the switch to telmisartan therapy. Study results show that telmisartan did not affect glycemic control, but it improved lipid metabolism and adiponectin production in patients with type 2 diabetes, suggesting that AT(1)-receptor antagonism and selective peroxisome proliferator-activated receptor-gamma activation by telmisartan combine to account for observed effects on lipid metabolism and adiponectin production.

To elucidate the role of visceral fat accumulation in the metabolic syndrome, differences in the pathology of the metabolic syndrome with or without visceral fat accumulation were investigated. A total of 472 prediabetic Japanese men (mean age, 47.5±7.2 yr) with impaired fasting glycemia (IFG) levels of 110–125 mg/dL were eligible for participation in the study. The study subjects were divided into the following four groups, and intergroup comparisons were made: group I without visceral fat area [VFA]≥100 cm2 but presenting with fewer than two other risk factors (i.e., TG≥150 mg/dL, HDL-C

We investigated the role of hypoadiponectinemia in the metabolic syndrome (MS), as well as its association with post-glucose challenge hyper-free fatty acidemia in the clinical setting. The study subjects comprised 177 corporate employees shown to have a fasting plasma glucose (FPG) level of 125 mg/dL or less in a 75 g OGTT in the corporation's healthcare center. When divided into those who met the Japanese criteria for the metabolic syndrome (MS group; n = 45) and those who did not (Non-MS group; n = 132), the MS group was shown to have significantly lower adiponectin levels than the Non-MS group, and tended to show higher high-sensitivity C-reactive protein (CRP) values than the Non-MS group, while not achieving statistical significance. The MS group showed higher baseline glucose levels; higher baseline, 30-, 60-, and 120-min post-challenge insulin levels; higher 30-, 60-, and 120-min post-challenge free fatty acid levels than the Non-MS group. Additionally, there was a significant, negative correlation between adiponectin levels, area under the free fatty acid curve, and area under the insulin curve at OGTT (r = -0.24, p0.01; r = -0.21, p0.01, respectively). When the patients were divided by adiponectin level into four groups to examine the number of risk factors for MS detected per patient and the incidence of MS, the lower the adiponectin level, the more risk factors were found per patient, with 68% of patients with an adiponectin level of less than 4 microg/mL found to have MS. In those with an adiponectin level of less than 4 microg/mL, BMI values, uric acid levels, HOMA-R values, and the number of risk factors for MS involved per patient were shown to be higher than in those with an adiponectin level of 4 microg/mL or greater. Furthermore, the following risk factors for MS were more frequently found in those with an adiponectin level of less than 4 microg/mL than in those with an adiponectin level of 4 microg/mL or greater: VFAor = 100 cm2 (OR 12.8, p0.001); TGor = 150 mg/dL (OR 3.2, p0.05); HDLC40 mg/dL (OR 1.9, p = 0.29); BPor = 130/85 mmHg (OR 2.2, p = 0.15); and FPGor = 110 mg/dL (OR 1.9, p = 0.29). Again, the incidence of MS (OR 7.6, p0.001) by the ATPIII criteria, as well as that by the Japanese criteria (OR 8.6, p0.001), was found to be higher in those with an adiponectin level of less than 4 microg/mL than in those with an adiponectin level of 4 microg/mL or greater. Our study results suggest that adiponectin is closely associated with the multiple risk factors that go to make up the MS, suggesting a role for hypoadiponectinemia as a surrogate marker for the MS and further appear to suggest that post-challenge hyper-free fatty acidemia may account in part for hypoadiponectinemia in the MS.

Impaired glucose tolerance (IGT) represents a prediabetic state positioned somewhere between normal glucose tolerance and diabetes, which is also assumed to make individuals in this state highly susceptible to atherosclerotic disease. IGT also accounts for a highly heterogeneous population, with the condition varying from individual to individual. In this study, we stratified subjects with IGT by their insulin response and compare the pathology of IGT when it is associated with high or low insulin response to gain insight into the diverse pathology of IGT. Of the male corporate employees who underwent 75 g OGTT at the corporation's healthcare center, 150 individuals diagnosed with IGT (isolated IGT, combined IGT and IFG) comprised our study subjects. The study subjects were stratified into four quartiles by percentile AUC for insulin, and those in the 25th or less percentile were defined as the low insulin response group (n = 37), vs those in the 76th or greater percentile defined as the high insulin response group (n = 38), and these groups were compared. There was no significant difference observed between the two groups in regard to post-OGTT glucose response and area under the glucose curve. However, the high insulin response group was associated with higher BMI, subcutanesous fat area, uric acid levels, HOMA-beta cell values, and delta insulin/delta glucose (30 min) than the low insulin response group. The number of risk factors for the metabolic syndrome detected (as defined by the ATPIII diagnostic criteria) per subject was 2.84 +/- 0.17 and 2.08 +/- 0.20, respectively, in the high insulin response group and in the low insulin response group, with the number significantly (p0.05) higher in the high insulin response group. Furthermore, the incidence of the metabolic syndrome as defined by the ATPIII diagnostic criteria was 63.2% (24/38) in the high insulin response group vs 32.4% (12/27) in the low insulin response group, with the incidence significantly (p0.01) higher in the high insulin response group. Likewise, the incidence of the metabolic syndrome as defined by the Japanese diagnostic criteria was found to be significantly (p0.05) higher in the high insulin response group at 50% (19/38) compared to 27.0% (10/37) in the low insulin response group. Our study findings suggest that IGT subjects with high insulin response and those with low insulin response vary greatly in regard to the number of atherosclerotic risk factors complicated and the frequency with which they are associated with the metabolic syndrome. It is also shown in middle-aged Japanese males that of the two forms of IGT, IGT with high insulin response is more closely linked to the pathogenesis of atherosclerotic cardiovascular disease.

To investigate the relationship between insulin resistance, postprandial hyperglycemia, postprandial hyperlipidemia, and oxidative stress in type 2 diabetes, changes in postprandial glucose, triglyceride, and nitrotyrosine levels vs baseline after diet loading were examined in type 2 diabetic patients given pioglitazone (PG) or glibenclamide (GB). Twenty-four outpatients with type 2 diabetes treated with oral PG for 6 mo (BMI, 26.3 +/- 0.9; HbA1c, 8.2 +/- 0.2%) and 10 type 2 diabetic patients treated with GB (BMI, 27.4 +/- 1.6; HbA1c, 8.1 +/- 0.2%) at our institutions were compared. These patients were given meal tolerance tests (MTT; each consisting of energy 400 kcal, protein 8.7 g, fat 22.4 g, carbohydrate 41 g) before and 6 mo after administration of either agent. PG produced a significant decrease in FPG, HbA1c, HOMA-R, and TG levels in the subjects compared to baseline. In contrast, GB significantly decreased FPG and HbA1c levels, while not affecting HOMA-R and TG values. While PG produced a significant increase in LPL, HDL-cholesterol, and adiponectin levels, GB did not affect these values. At MTT 6 mo after PG administration, insulin levels before and 4 h after MTT, free fatty acid (FFA) levels 1, 2, and 4 h after MTT, glucose, TG, and RLP-TG levels before and 1, 2, 4, and 6 h after MTT were significantly decreased compared to baseline. At MTT 6 mo after GB administration, while a significant decrease in fasting and 2 h, postprandial glucose values compared to baseline MTT levels was observed, fasting and postprandial TG and RLP-TG levels remained unchanged compared to baseline. After 6 mo of PG and GB administration, serum nitrotyrosine levels before and after MTT were significantly decreased compared to baseline in both groups, while the decrease in nitrotyrosine levels before and after MTT was more marked in the subjects given PG. Our study results suggest that PG suppresses increases in postprandial glucose and TG levels, and improves insulin resistance; and, in addition, that PG may have a favorable impact on oxidative stress in type 2 diabetic patients.

Our study evaluated the relationship between the pathologic changes associated with atherosclerosis, as primarily represented by postprandial remnant-like lipoproteins and carotid intima-media thickness (IMT), in type 2 diabetic patients. Meal tolerance tests (MTT) were performed in 68 patients with type 2 diabetes. The subjects were divided by pre-meal and 2-h postprandial triglyceride (TG) levels into the normotriglyceridemia (NTG) group; the postprandial hypertriglyceridemia (PHTG) group; and the fasting hypertriglyceridemia (FHTG) group. HOMA-R values were significantly higher in the FHTG group than in the NTG group, with the plasma pre-heparin LPL mass and serum adiponectin levels in the FHTG and PHTG groups significantly lower than in the NTG group. One- and two hour postprandial RLP-TG levels were significantly higher in the PHTG group than in the NTG group, while there was no significant difference in postprandial glucose levels between the two groups. The IMT values were significantly higher in both the FHTG and PHTG groups than in the NTG group. Logistics regression analysis of the 1- and 2-h RLP-TG values using IMT as an induced variable showed the odds ratio for high IMT values to be 5.17 (p0.05) for the 1-h RLP-TG values and 3.01 (p = 0.105) for the 2-h RLP-TG values. Our study results suggest that delayed TG metabolism leading to the retention of remnants in type 2 diabetic patients appears to be closely associated with atherosclerosis, and that postprandial hyperlipidemia is an independent risk factor for the early onset of atherosclerosis.

Objective: Short-term hypoglycemic effects of single-dose voglibose and nateglinide were compared after sucrose loading in spontaneously diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Materials and Methods: After a 17-h fasting period, the animals received 0.06 mg/kg of voglibose (VOG group, n=6), 50 mg/kg of nateglinide (NAT group, n=6), or 0.5% methyl cellulose (control group, n=6), immediately followed by 2.5 g/kg of sucrose. Results: Compared to control group values, glucose levels after sucrose loading were significantly decreased in the portal blood in the VOG group and in the peripheral blood in the NAT and VOG groups. The portal glucose AUC0−120 min was significantly lower in the VOG group than in the control and NAT groups, whereas the peripheral glucose AUC0−120 min was significantly lower in the VOG and NAT groups than in the control group. Portal insulin levels in the VOG group were significantly decreased compared to the control group. However, portal insulin levels in the NAT group were acutely increased, peaking 15 min after sucrose loading. Portal FFA levels were decreased in the NAT group 15, 30, and 60 min after sucrose loading; no FFA reductions were seen in the VOG group. Conclusions: Although both drugs produced similar hypoglycemic effects after sucrose loading in the peripheral blood, these drugs generated vastly different results in portal blood. Reduced FFA in the portal blood, observed after single administration of nateglinide, may have a favorable impact not only on glucose metabolism but also on lipid metabolism.