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To investigate the anatomical and functional changes in areas containing paravascular abnormalities (PVA) in eyes with epiretinal membrane (ERM) after surgery. Twenty-eight eyes with concurrent idiopathic ERM and PVA were enrolled in this prospective study. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and areas of PVA in the superficial and deep capillary levels detected on en face optical coherence tomography were measured preoperatively and 1, 3, and 6 months postoperatively. Retinal sensitivity in selected PVA lesions was evaluated by microperimetry preoperatively and 1 and 6 months postoperatively. The areas of PVA at the superficial capillary level before and 1, 3, and 6 months after surgery measured 1.65 ± 1.27, 0.44 ± 0.62, 0.40 ± 0.64, and 0.38 ± 0.62 mm2, respectively, while those at the deep capillary level measured 0.27 ± 0.57, 0.10 ± 0.26, 0.09 ± 0.29, and 0.05 ± 0.15 mm2, respectively. The areas of PVA in the superficial and deep capillary levels were significantly smaller postoperatively (all p

Summary Fluid loss is significant for the standard fracturing fluids without adding solid materials. One method to reduce fluid loss is to add silica flour, although it reduces fracture conductivity. Other methods are to use wall-building polymers. However, the fluid loss is still significant, and complete removal of wall-building materials is not possible, even with breakers. We found that powder, granular, and fibrous materials made of polyglycolic acid (PGA) or polylactic acid (PLA) are very suitable for fluid-loss agents because PGA is stronger than steel and PLA is as strong as rock, although they dissolve as liquid acids after applications. Fluid-loss tests are conducted with the standard American Petroleum Institute slot tester and filtrate-loss tester, mixing powders, grains, and fiber, all made of PGA or PLA in fracturing polymer fluids. The ratio of grains, powder, and fiber is optimized to minimize fluid loss for porous media and fractured porous media. Then, the changes of particle size are measured under heated conditions. Fracture-simulation studies are also conducted with a 3D fracture-boundary element model to compare the fluid efficiency of the fracturing fluids with and without the PLA and PGA particles. The results show that the capability of preventing fluid loss and plugging microcracks is maintained for the porous filters and small slots within a reasonable time period. For short-term applications less than 3 hours, both PGA and PLA fluid-loss agents are stable when the temperature is less than 212°F. Mixing these materials often provides more-efficient properties to reduce fluid loss and to bridge microcracks. No residues are left after experiments if the fracturing fluid is kept heated for 24 hours. The amount of the PGA and PLA fluid-loss agents required to reduce the fluid loss is not significant. Hence, their field applications are feasible, judging the cost and the benefit. The advantage in using these materials is that they turn from solid to liquid after applications so that no formation damage and no proppant-conductivity damage occur. The fluid loss is also significantly reduced with the powder particles. In addition, because the PGA and PLA materials are degradable, solids with arbitrary sizes and shapes may be used as long as they control fluid loss and plug fine fractures. Their applications are not only limited to reducing fluid loss, but one may also use them for engineering fracture design to enhance the fracture conductivity.

Background The precise pathologic mechanisms underlying human thoracic aortic aneurysms (TAAs) remain uncertain, except that matrix metalloproteinase-9 (MMP-9) is considered a key enzyme for the degradation of extracellular matrix in aneurysm walls. The aim of this study was to elucidate the significance of the angiotensin II (AngII) pathway to MMP-9 production in human TAA walls. Methods and results We examined the activation of Smad2, a common downstream molecule of AngII and transforming growth factor β (TGF-β) pathways, and the expression of MMP-9 in human nonsyndromic TAA walls. We observed significant increases in Smad2 activation and MMP-9 expression, associated with disruption of elastic lamellae. Using human TAA walls in ex vivo culture, we investigated whether AngII and/or TGF-β pathways are essential for MMP-9 production. Unexpectedly, TGF-β receptor inhibitor had no effect on MMP-9 production. We used PD98059, an inhibitor of extracellular signal–regulated kinase (ERK) activation, and demonstrated that PD98059 dramatically reduced MMP-9 production with attenuation of Smad2 activation. Moreover, exogenous AngII resulted in increases in Smad2 activation and MMP-9 production, in an ERK-dependent manner. Conclusion Our findings indicate that the AngII/ERK pathway has an important role in the production of MMP-9 in human nonsyndromic TAA walls.

We sought to examine the effect of resveratrol (3,4',5-trihydroxy-trans-stilbene), a plant-derived polyphenolic compound, on the development of abdominal aortic aneurysm (AAA).AAA was induced in mice by periaortic application of CaCl(2). NaCl (0.9%)-applied mice were used as a sham group. Mice were treated with intraperitoneal injection of PBS (Sham/CON, AAA/CON, n=30 for each) or resveratrol (100 mg/kg/day) (AAA/RSVT, n=30). Six weeks after the operation, aortic tissue was excised for further examinations.Aortic diameter was enlarged in AAA/CON compared with Sham/CON. Resveratrol treatment reduced the aneurysm size and inflammatory cell infiltration in the aortic wall compared with AAA/CON. Elastica Van Gieson staining showed destruction of the wavy morphology of the elastic lamellae in AAA/CON, while it was preserved in AAA/RSVT. The increased mRNA expression of monocyte chemotactic protein-1, tumor necrosis factor-α, intercellular adhesion molecule-1, CD68, vascular endothelial growth factor-A, p47, glutathione peroxidase (GPX)1 and GPX3 were attenuated by resveratrol treatment (all p0.05). Administration of resveratrol decreased protein expression of phospho-p65 in AAA. The increased 8-hydroxy-2'-deoxyguanosine-positive cell count and 4-hydroxy-2-nonenal-positive cell count in AAA were also reduced by resveratrol treatment. Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was lower in AAA/RSVT compared with AAA/CON (both p0.05). Compared with AAA/CON, Mac-2(+) macrophages and CD31(+) vessels in the aortic wall were decreased in AAA/RSVT (both p0.05).Treatment with resveratrol in mice prevented the development of CaCl(2)-induced AAA, in association with reduced inflammation, oxidative stress, neoangiogenesis, and extracellular matrix disruption. These findings suggest therapeutic potential of resveratrol for AAA.

The effects of nilvadipine on intimal thickness in expanded poly-tetrafluoroethylene grafts were examined in 21 rabbits undergoing infrarenal aorta reconstruction. Seven rabbits received commercial rabbit chow (control group), seven, a regular diet supplemented with 1% cholesterol (cholesterol group); and seven, the cholesterol diet with 98.9% pure nilvadipine 1 mg/kg/day (nilvadipine group). Grafts were harvested 3 months after surgery for histologic examination. Intimal thickness at the proximal and distal anastomosis was, respectively, 225±76 and 273±110 m in the control group, 525±236 and 600±250 m in the cholesterol group, and 284±94 and 241±86 m in the nilvadipine group. Intimal thickness in the cholesterol group was significantly greater than in the nilvadipine group (p

A synthetic pseudo-ceramide (SLE66) has been shown to improve dryness/itching of human skin. The objective of this study was to investigate metabolism, genotoxicity and cytotoxicity of SLE66. Pharmacokinetic profile of [14C]-SLE66 was investigated following oral or transdermal administration to Sprague-Dawley rats. The plasma radioactivity following oral administration (1000 mg SLE66/kg) reached maximum (Cmax--39.77 µg eq/ml) at 4 h and then declined with apparent elimination half-life of 23.6 h. Following transdermal application of [14C]-SLE66 (1000 mg/kg) or as prescription formulation (8%; 160 mg/kg) to normal skin-rats, no radioactivity was noted in plasma, while in damaged skin-rats, trace amount of plasma radioactivity was detected for up to 8 h. The radioactivity excreted in urine, feces, and expiratory air collected for up to 24 h accounted for 5.7, 84.8, and 0.6%, respectively. In the cytotoxicity experiments, SLE66 did not cause toxicity in human skin model. In the genotoxicity studies, SLE66 was not mutagenic in Ames assay and chromosomal aberration assay. These results suggest that following oral administration a small amount of SLE66 is absorbed and excreted in urine, while no absorption was noted after transdermal application to normal skin and SLE66 does not cause cytotoxicity or genotoxicity.

AF64A, a specific cholinergic neurotoxin, was injected into the basal nuclei of rats. The injected sites were the bilateral nucleus basalis of Meynert (NBM) and the medial septal nucleus (MSN), well known to be the nuclei of origin of the two major cholinergic pathways. The remote effects of injection were estimated by the regional choline acetyltransferase (CAT) activity in the frontal cortex, striatum and hippocampus. The injection of AF64A (1 nmol in 1 microliter) produced a reduction in the CAT activity in each projected site: NBM lesions in the frontal cortex and MSN lesions in the hippocampus after one and three weeks. Twelve weeks after the injection, the reduced CAT activity had returned to normal levels. This neurochemical effect shows plasticity and recovery with time. The injections of small amounts of AF64A (0.2 and 0.1 nmol in 1 microliter) produced no chemical changes after one week.

Toll-like receptor 4 (TLR4) and angiotensin II (AngII) induce vascular remodeling through the production of reactive oxygen species (ROS). AngII has also been shown to increase antioxidant enzyme extracellular superoxide dismutase (ecSOD). However, the roles of TLR4 in Ang II-induced ROS production, vascular remodeling and hypertension remain unknown. Mice lacking TLR4 function showed significant inhibition of vascular remodeling in response to chronic AngII infusion, with no impact on blood pressure. The increases in ROS level and NADPH oxidase activity in response to AngII infusion were markedly blunted in TLR4-deficient mice. Similar effects were observed in wild-type (WT) mice treated with a sub-depressor dose of the AT1 receptor antagonist irbesartan, which had no effects on TLR4-deficient mice. Intriguingly, the AngII infusion-induced increases in ecSOD activity and expression were rather enhanced in TLR4-deficient mice compared with WT mice, whereas the expression of the proinflammatory chemokine MCP-1 was decreased. Importantly, AngII-induced vascular remodeling was positively correlated with NADPH oxidase activity, ROS levels and MCP-1 expression levels. Notably, chronic norepinephrine infusion, which elevates blood pressure without increasing ROS production, did not induce significant vascular remodeling in WT mice. Taken together, these findings suggest that ROS elevation is required for accelerating vascular remodeling but not for hypertensive effects in this model. We demonstrated that TLR4 plays a pivotal role in regulating AngII-induced vascular ROS levels by inhibiting the expression and activity of the antioxidant enzyme ecSOD, as well as by activating NADPH oxidase, which enhances inflammation to facilitate the progression of vascular remodeling.

We previously developed two new MRI phantoms (called the CAG phantom and the CAGN phantom), with T1 and T2 relaxation times equivalent to those of any human tissue at 1.5 T. The conductivity of the CAGN phantom is equivalent to that of most types of human tissue in the frequency range of 1 to 130 MHz. In this paper, the relaxation times of human tissues are summarized, and the composition of the corresponding phantoms are provided in table form. The ingredients of these phantoms are carrageenan as the gelling agent, GdCl3 as a T1 modifier, agarose as a T2 modifier, NaCl (CAGN phantom only) as a conductivity modifier, NaN3 as an antiseptic, and distilled water. The phantoms have T1 values of 202-1904 ms and T2 values of 38-423 ms when the concentrations of GdCl3 and agarose are varied from 0-140 micromol/kg, and 0%-1.6%, respectively, and the CAGN phantom has a conductivity of 0.27-1.26 S/m when the NaCl concentration is varied from 0%-0.7%. These phantoms have sufficient strength to replicate a torso without the use of reinforcing agents, and can be cut by a knife into any shape. We anticipate the CAGN phantom to be highly useful and practical for MRI and hyperthermia-related research.

The authors developed a phantom, designated as the CAGN phantom, compatible for MRI and hyperthermia that is useful in the fundamental studies of non-invasive MR thermometry. The ingredients of this phantom are carrageenan, GdCl3 as a T1 modifier, agarose as a T2 modifier, NaCl as a conductivity modifier, NaN3 as an antiseptic and distilled water. Another phantom that was developed, the CAG phantom, has relaxation times that are adjustable to those of any human tissue. To use this phantom for electromagnetic heating, NaCl was added to change the conductivity of the phantom and clarified the relationship between the conductivity and NaCl concentration. This study examined the relationship between relaxation times and NaCl concentration of the CAGN phantom. The results showed that both T1 and T2 values were affected by NaCl and the experimental results led to the empirical formulae expressing the relationship between the relaxation rates (1/T1, 1/T2) and the concentrations of GdCl3, agarose and NaCl. The appropriate concentrations of T1 and T2 modifiers were calculated from these empirical formulae when making a specified phantom that has the required relaxation times and NaCl concentration.

A phantom has previously been developed containing carrageenan, agarose and gadolinium chloride (called CAG phantom) for MRI with 1.5 T. T(1) and T(2) relaxation times of this phantom are independently changeable by varying concentrations of relaxation-time modifiers to simulate relaxation times of the various types of human tissues. The CAG phantom has a T(1) value of 202-1904 ms and a T(2) value of 38-423 ms, when the GdCl(3) concentration is varied from 0-140 micromol/kg and the agarose concentration is varied from 0-1.6%. A new phantom has now been developed (called CAGN phantom), made by adding an electric conductive agent, NaCl, to the CAG phantom for use in the areas of MRI and hyperthermia research. Dielectric properties of the CAGN phantom were measured and the results of experiments were expressed by the Cole-Cole equation in the frequency range of 5-130 MHz. The relationship between the conductivity of the CAGN phantom and the concentration of NaCl was expressed by a linear function in the frequency range of 1-130 MHz. The linear function involves a parameter of frequency and, when the frequency is 10 MHz, the conductivity of the CAGN phantom can be changed from 0.27-1.26 Sm(-1) by increasing the NaCl concentration from 0-0.7%. The CAGN phantom developed can be employed in basic experiments for non-invasive temperature measurement using MRI and as a loading phantom for MRI with up to 3 T.

A new tissue-equivalent MRI phantom based on carrageenan gel was developed. Carrageenan gel is an ideal solidifying agent for making large, strong phantoms in a wide variety of shapes. GdCl(3) was added as a T(1) modifier and agarose as a T(2) modifier. The relaxation times of a very large number of samples were estimated using 1.5-T clinical MRI equipment. The developed phantom was found to have a T(1) value of 202-1904 ms and a T(2) value of 38-423 ms when the GdCl(3) concentration was varied from 0-140 mumol/kg and the agarose concentration was varied from 0-1.6% in a carrageenan concentration that was fixed at 3%. The range of measured relaxation times covered those of all types of human tissue. Empirical formulas linking the relaxation time with the concentration of the modifier were established to enable the accurate and easy calculation of the modifier concentration needed to achieve the required relaxation times. This enables the creation of a phantom having an arbitrary combination of T(1) and T(2) values and which is capable of retaining its shape.

Fluid-loss is significant for the standard fracturing-fluids without adding solid materials. One method to reduce fluid-loss is to add silica flour, although it reduces fracture conductivity. Other methods are to use wall building polymers. However, the fluid-loss is still significant and complete removal of wall building materials are not possible even with breakers. We found that powder, granular and fibrous materials made of Polyglycolic Acid (PGA) or Polylactic Acid (PLA) are very suitable for fluid-loss agents since they are as strong as rock, while they dissolve as liquid acids after applications. Fluid-loss tests are conducted using the standard API slot tester and filtrate loss tester, mixing powders, grains and fiber, all made of PGA or PLA in frac polymer fluids. Ratio of grains, powder and fiber is optimized to minimize fluid-loss for porous media and fractured porous media. Then, the changes of particle size are measured under heated conditions. Fracture simulation studies are also conducted using a 3D fracture boundary element model to compare the fluid efficiency of the fracturing fluids with and without the PLA and PGA particles. The results show that the capability of preventing fluid-loss and plugging micro-cracks is maintained for the porous filters and small slots within reasonable time period. For short term applications less than 3 hours, both PGA and PLA fluid-loss agents are stable when the temperature is less than 212 °F. Mixing these materials often provides more efficient properties to reduce fluid-loss and to bridge micro-cracks. No residues are left after experiments if the fracturing fluid is kept being heated for 24 hours. The amount of the PGA and PLA fluid-loss agents required to reduce the fluid-loss is not significant. Hence, their field applications are feasible judging the cost and the benefit. The advantage in using these materials is that they turn from solid to liquid after applications so that no formation damage and no proppants conductivity damage occurs. The fluid-loss is also significantly reduced with the powder particles. In addition, because the PGA and PLA materials are degradable, solids with arbitrary sizes and shapes may be used as long as they control fluid-loss and plug fine fractures. Their applications are not only limited to reducing fluid-loss but they may be used for engineering fracture design to enhance the fracture conductivity.

Highly congested thiophenes, 3,4-di-tert-butyl-, 3,4-di(1-adamantyl)-, 3,4-dineopentyl-, and 3-(1-adamantyl)-4-tert-butylthiophenes (4a−d), were prepared in satisfactory overall yields by intramolecular reductive coupling of 3-thiapentane-1,5-diones (1a−d) followed by acid-catalyzed dehydration of the resulting thiolane-3,4-diols (2a−d). Experimental procedures of this thiophene synthesis are fully described. Oxidation of the thiophenes 4a−d with m-CPBA gave the corresponding thiophene 1,1-dioxides 13a−d in good yields. The Diels−Alder reactions of 13a−d with phenyl vinyl sulfone gave o-di-tert-butyl-, o-di(1-adamantyl)-, o-dineopentyl-, and o-(1-adamantyl)-tert-butylbenzenes (17a−d) directly in high yields with loss of benzenesulfinic acid and sulfur dioxide. The dioxides 13a−d also underwent Diels−Alder reactions with alkynic dienophiles to give the corresponding benzene derivatives carrying two bulky substituents on adjacent positions. Pyridazines 25b,c, carrying bulky substituents on the 4- and 5-posi...

本研究では,ニンジンの師部,形成層部,ならびに木部の各組織から切断方向の異なる切片を調製し,生理特性やカルス形成速度の相違などを調べることによりカットニンジンの貯蔵性に差異の生じる理由を明らかにしようとした.切断方向にかかわらず,師部と形成層部の切片のCO2排出量とC2H4生成量は切断後10数時間まで増加し,その後は減少した.木部切片のCO2排出量とC2H4生成量は切断直後から実験終了の保持48時間まで増加を示した.形成層部切片のCO2排出量とC2H4生成量の一時的な増加ならびに木部切片が示したCO2排出量とC2H4生成量の保持に伴う経時的な増加は,いずれも縦切り切片の方が輪切り切片より多かった.木部切片における生菌数の増加は師部切片より速く,組織が異なっても縦切り切片における生菌数の増加は輪切り切片より速かった.カルス形成量は形成層部切片で最も多く,師部切片がそれに続き,木部切片におけるカルス形成量が最も少なかった.組織が異なっても輪切り切片のカルス形成量は縦切り切片より多かった.木部から調製した切片は,師部切片より生理活性が高く,微生物の繁殖が速く,カルス形成量が少なかった.また同じ組織から切片を調製するときには,維管束に直角に調製した切片の方が平行に調製した切片よりも生理活性が低く,微生物の繁殖が遅く,カルス形成量が多かった.このような組織間ならびに切断方向による諸特性の相違がカットーンジンの貯蔵性に差異を生じさせるものと思われた.

The C2H4 treatment induced the occurrence of bitterness and the brown pitting injury in partially processed carrot (PPC) during storage at 20 °C.The pitting injury was more apparent in the inner-phloem than in other tissues. Untreated PPC did not show apparent changes of o-diphenols and isocoumarin. The accumulations of o-diphenols and isocoumarin were greatest in outer- and inner-phloem and were followed by the cambium, cortex and xylem of treated PPC. The C2H4 treatment induced the apparent decrease in non-reducing sugar and the increase in reducing sugar of all tissue.

Effects of cultural variety (cultivar, cv) and storage temperatures on the changes of quality in fresh-cut sweet pepper (Capsicum annuum L. var. angulosum Miller) fruit were studied with reference to the physiological and chemical changes. Bell pepper fruits, 'New Ace', green; 'Wonder Bell', red; 'Golden Bell', yellow, were prepared in ring (crosswise cut sections 10 mm in width) and line (lengthwise cut sections 10 mm in width) sections, respectively. They were packaged hermetically in low density polyethylene bags (0.02mm thick) and stored at 1°C, 4°C, 8°C or 20°C. The softening and decay of sections in all cultivars began from the cut surface with these changes being slowest in the green section and fastest in the yellow one during storage at 1°C and 20°C. The deterioration rate was slower in the ring section than in the line one of all cultivars. The increase of CO2 and decrease of O2 concentrations in the package of the yellow section were fastest and were followed by red and green ones, and these changes were faster in the line section than in the ring one of all cultivars. Ascorbic acid (AsA) content showed a minimal change in all sections for the experiment period.The deterioration of sections, the increase of CO2 and C2H2, and the decrease of O2 concentrations were observed during storage at 20°C, but the sections stored at 1°C, 4°C and 8°C did not show significant changes. The contents of AsA and chlorophyll in all sections showed almost no change before decay during storage at all temperatures.

Fresh-cut green bananas (non-C2H4 treated) were prepared in the following four styles : 7cm-long and 1cm-thick sections cut longitudinally (LCS), 1cm-thick crosswise sections cut transversely (0 CCS), and cut obtusely to the transverse at 30° (30 CCS) or 60° (60 CCS). Each section packed in polyethylene bags was stored at 20°C. I. The cut surface area and weight of LCS were the largest, followed by 60 CCS, 30 CCS, and 0 CCS, but no major differences were found in the ratio of the surface area/weight among sections. 2. The color in the peel of all sections changed during 6 days storage. The LCS began to yellow most rapidly, followed by 30 CCS, 60 CCS, and 0 CCS. The concentrations of C2H4 and CO2 in polyethylene (PE) bags were the highest with LSC and those of the CCSs increased with increasing the obtuse angles until day 3. 3. The respiration rate (CO2 production) of the intact green bananas increased slowly during 7 days storage. The respiration rate of LCS increased rapidly, and that of CCSs increased until day 4, the increase being greater in 60 CCS. Ethylene production was not detectable from intact green bananas during 6 days storage. The LCS showed the increase of C2H4 production and the peak of production was on day 2. The 60 CCS showed the peak on day 3 and the C2H4 production rate of the 30 and 0 CCS reached the peak on day 5. The peak of 30 CCS was higher than that of 0 CCS. 4. There were significant linear increase in sugar content and decrease in starch content of pulp in all sections during 6 days storage. The LCS showed these changes most rapidly followed by 60 CCS, 30 CCS, and 0 CCS. 5. It appears that the cutting of green banana fruits induces the activation of physiological and chemical changes, and these changes are associated with cutting direction.

本研究では'清見'果実のこはん症発生に伴うK+漏出量ならびに組織構造の変化を調べた。ごはん症は8℃へ昇温するより20℃に昇温した'清見'に顕著に現礼ポリエチレン包装によって軽減された。20℃へ昇温した果実のK+漏出量は障害発生時に急増し, 増加は8℃へ昇温した場合より多かった。両昇温区とも無包装'清見'のK+漏出量は包装果実の漏出量より多かった。走査型電子顕微鏡による観察では, '清見'のこはん症の陥没は油胞間の表皮から数層内部の柔組織細胞の変形によって引き起こされ, 表皮細胞や油胞の破壊によって陥没するのではないことが明らかとなった。

The occurrence of bitterness, changes in the production of bitter compounds, and sugar contents were measured to determine the effects of ethylene (C2H4) treatment and/or cutting on different tissues (different part of phloem or xylem) of partially processed carrot (PPC) during storage. Carrots (Daucus carota L. var. sativa DC, cv : unknown) were sliced with 1 cm thickness and stored at 20°C with or without C2H4 (100ppm) in air. Phloem or xylem of PPC were divided into three portions (A : part located at 0-1.5mm from cut surface, B : 1.5-3.0 mm, and C : 3.0-5.0), respectively, and the occurrence of bitterness and contents of phenols and sugar in these portions were determined. Neither C2H4-treated nor un-treated PPC showed apparent decay during 3 days of storage, but brown pitting injury on the surface of phloem was markedly associated with C2H4 treatment. This was not so for xylem tissue. The occurrence of bitterness increased apparently in phloem treated with CO2H4 and the xylem was less sensitive than phloem. Bitterness in A was significant and moderate in B and C of phloem. The contents of isocoumarin and phenols, bitter compounds, did not show apparent changes in phloem and xylem of un-treated PPC. The accumulation of these compounds were induced significantly in phloem and moderately in xylem by C2H4 treatment. This increase was greatest in A, followed by B and C in both tissues. An increase in reducing sugar content and a decrease in total sugar content were observed in phloem but not in xylem of C2H4 treated PPC, while neither phloem nor xylem in un-treated PPC showed apparent changes during storage. We conclude that the occurrence of bitterness and the accumulation of bitter compounds in PPC are induced by C2H and cutting and propose the importance of PPC storage without C2H4.

The C2H4 induced the occurrence of bitterness and the pitting injury and the combination of low O2 (4%) and high CO2 (18%) in the atmosphere suppressed these changes apparently in partially processed carrot (PPC).The PPC showed a decrease in the contents of soluble total sugar (TS) and non-reducing sugar (NRS) and the increase of reducing sugar (RS) by C2H4 treatment during holding at 20°C. The low O2 or high CO2 in the atmosphere delayed the decrease of TS and NRS and the increase of RS induced by C2H4 (20ppm) and the combination of low O2 and high CO2 in the atmosphere suppressed these changes apparently during 5 days holding at 20°C.

本研究では, ニンジンの保持に伴う苦味形成やその関連物質の生成に及ぼす組織に対する機械的損傷ならびに保持環境ガス中のエチレン (C2H4) の影響を調べた。機械的損傷を受けたニンジンの苦味形成はC2H4処理によって同一個体内の傷害部で最も顕著に現れ次いで障害を与えなかった師部に現れたが木部での苦味形成は少なく, C2H4処理を行わなかった場合はいずれの部位でも苦味形成は認められなかった。また損傷を受けなかったニンジンでは苦味は形成されなかった。苦味関連物質であるイソクマリン含量は機械的損傷を受けてC2H4処理されたニンジンの傷害部で顕著に増加したが, 健全部の師部や木部での増加は少なかった。損傷を受けなかったニンジンにC2H4処理を行ってもイソクマリン含量の増加は誘導されず, 損傷を受けたがC2H4処理を行わなかったニンジンや損傷を受けずC2H4処理されなかったニンジンではイソクマリンの蓄積はみられなかった。損傷を受けたニンジンをC2H4処理すると, 傷害部でのフェノール物質の蓄積ならびに全糖含量と非還元糖含量の減少および還元糖の増加が誘導された。他の実験区でのこれらの含量変化は少なかった。ニンジンの流通過程における苦味形成は, 保持環境ガス中のC2H4ならびに個体の機械的損傷によって促進されることが明らかとなった。

Angiotensin II (AngII) increases reactive oxygen species (ROS) and induces glomerular sclerosis. Toll-like receptor 4 (TLR4)-mediated inflammation enhances the renal impairment in renal inflammatory diseases. The relationship between TLR4 and AngII-induced glomerular sclerosis is unknown. We

3,4-Dineopentylthiophene ( 4 ) was synthesized in a good overall yield starting from methyl neopentyl ketone. 3,4-Dineopentylthiophene-1,1-dioxide ( 5a ), easily obtainable by oxidation of 4 , undergoes Diels-Alder reactions with a variety of acetylenic dienophiles or their equivalent to furnish aromatic compounds carrying two neopentyl groups on adjacent positions.

Aims Increased angiogenesis, chronic inflammation, and extracellular matrix degradation are the major pathological features of abdominal aortic aneurysm (AAA). We sought to elucidate the role of vascular endothelial growth factor (VEGF)-A, a potent angiogenic and proinflammatory factor, in the development of AAA. Methods and results Human AAA samples showed increased VEGF-A expression, neovascularization, and macrophage infiltration compared with normal aortic walls. AAA was induced in mice by periaortic application of CaCl2. AAA mice were treated with soluble VEGF-A receptor (sFlt)-1 or phosphate-buffered saline and sacrificed 6 weeks after the operation. Treatment with sFlt-1 resulted in reduced aneurysm size, restored wavy structure of the elastic lamellae, reduced Mac-2+ monocytes/macrophages, CD3+ T-lymphocytes, and CD31+ vessels, and attenuated matrix metalloproteinase (MMP)-2 and 9 activity in periaortic tissue of AAA. Increased aortic mRNA expression of monocyte chemotactic protein-1, tumour necrosis factor-α, and intercellular adhesion molecule-1 in AAA was attenuated by sFlt-1 treatment. Conclusion VEGF-A was overexpressed in the aortic wall of human and experimental AAA. Treatment with sFlt-1 inhibited AAA development in mice, in association with reduced neoangiogenesis, infiltration of inflammatory cells, MMP activity, and extracellular matrix degradation. These findings suggest a crucial role of VEGF-A in the development of AAA.

Partially processed carrots were prepared as two styles, lengthwise cut sectionsdivided into eight equal parts (1/8 LCS) and crosswise cut sections with 1cm thickness (1 CCS). These sections and whole carrots were exposed to continuous flow of atmosphere with or without 100ppm ethylene in air at 20°C. In 1/8 LCS and 1 CCS the occurrence of bitterness and astringency, the appearance of brown pitting injury in cut surface, the formation of isocoumarin responsible for bitterness, and rapid increase of phenols were induced by ethylene during 5days storage, whereas, these changes were not noted in whole carrots exposed to ethylene, 1/8 LCS and 1 CCS exposed to air. Partially processed carrots of 1/4 LCS were sealed in low density polyethylene (0.05mm thickness) or polypropylene (0.025mm thickness) bags into which 100ppm ethylene was injected and stored at 20°C. Ethylene did not induce bitterness of carrot in both bags during 10days storage.It is possible that the decrease of O2 concentration and the increase of CO2concentration in bags were responsible for the inhibition of producing bitter compounds by ethylene.

3,4-Dineopentylthiophene ( 4 ) was synthesized in a good overall yield starting from methyl neopentyl ketone. 3,4-Dineopentylthiophene-1,1-dioxide ( 5a ), easily obtainable by oxidation of 4 , undergoes Diels-Alder reactions with a variety of acetylenic dienophiles or their equivalent to furnish aromatic compounds carrying two neopentyl groups on adjacent positions.

SLE66 a synthetic pseudo-ceramide, has been shown to reduce dryness/scaling/itching of human skin. Naturally occurring ceramides have been claimed to play a crucial role in cell proliferation, differentiation, and apoptosis including processes important for embryogenesis. The objective of this study was to evaluate the potential maternal and fetal effects of SLE66. SLE66 was administered orally (gavage) to mated female Crl:CD®(SD)IGS BR rats (25/group) once daily from gestation day 6 through 19, at dose levels of 0 (control), 150, 400 or 1000 mg/kg/day. No treatment-related clinical or internal (macroscopic) findings were noted and all animals survived to the scheduled necropsy on gestation day 20. SLE66 administration did not affect mean maternal body weights, body weight gains, net body weights, net body weight gains, gravid uterine weights, or feed consumption. Similarly, SLE66 administration did not affect intrauterine growth and survival related parameters such as viable fetuses, pre-implantation loss, early and late resorptions, fetal weight and fetal sex. No SLE66-related fetal malformations or developmental variations were noted. Based on the results of this study, a dose level of 1000 mg/kg/day (highest dose used) was considered as the no-observed-adverse-effect level (NOAEL) for both maternal and developmental toxicity.

The aim of the study was to evaluate whether aqueous humor levels of asymmetric dimethylarginine (ADMA) are associated with monocyte chemoattractant protein-1 (MCP-1).Aqueous humor levels of ADMA and MCP-1 were measured by high-performance liquid chromatography (HPLC) and ELISA, respectively, in 31 uveitis samples and nine cataract control samples.Aqueous humor ADMA and MCP-1 levels were significantly higher in infectious or non-infectious uveitis patients than in controls (0.67+/-0.04 nmol/ml vs 0.55+/-0.03 nmol/ml vs 0.43+/-0. 04 nmol/ml (p0.01) and 29.0+/-11.3 ng/ml vs 4.5+/-1.2 ng/ml vs 0.47+/-0.1 ng/ml (p0.01), respectively). A positive correlation between ADMA and MCP-1 levels in aqueous humor was found in control and uveitis patients (r = 0.33, p0.05).The results demonstrated that aqueous humor levels of ADMA were positively associated with MCP-1 in humans. Our present observations suggest that aqueous humor levels of ADMA may be a novel biomarker of inflammation in uveitis.

The type 1 protein phosphatase (PP1) has been reported to be overactivated in the failing heart, leading to a depression in cardiac function. We investigated whether in vivo PP1 inhibition by myocardial gene transfer of inhibitor-2 (INH-2), an endogenous PP1 inhibitor, alleviates heart failure (HF) progression in the cardiomyopathic (CM) hamster, a well-established HF model. Adenoviral INH-2 gene delivery improved % fractional shortening of the left ventricle (LV) accompanied by reduced chamber size at 1 wk. In vivo myocardial INH-2 gene delivery induced an increase in cytosolic PP1 catalytic subunit alpha (PP1Calpha) without inducing the corresponding increase in cytosolic PP1 activity. On the other hand, INH-2 delivery induced a decrease in microsomal PP1Calpha, resulting in a preferential decrease in microsomal PP1 activity, thereby increasing in phospholamban phosphorylation at Ser16. INH-2 gene transfer alleviated brain natriuretic peptide expression, presumably reflecting improved cardiac function. Moreover, adeno-associated virus-mediated INH-2 gene delivery significantly extended the survival time for 3 mo. These results indicate that increased PP1 activity is an exacerbating factor during progression of genetic cardiomyopathy and modulation of PP1 activity by INH-2 provides a potential new treatment for HF without activating protein kinase A signaling in cardiomyocytes.

Although oxidative stress causes activation of c-Jun N-terminal kinase (JNK) and apoptosis in many cell types, how the JNK pathway is connected to the apoptosis pathway is unclear. The molecular mechanism of JNK-mediated apoptosis was investigated in adult rat cardiac myocytes in culture as a model system that is sensitive to oxidative stress. Oxidative stress caused JNK activation, cytochrome c release, and apoptosis without new protein synthesis. Oxidative stress-induced apoptosis was abrogated by dominant negative stress-activated protein kinase/extracellular signal-regulated kinase kinase-1 (SEK1)-mediated inhibition of the JNK pathway, whereas activation of the JNK pathway by constitutively active SEK1 was sufficient to cause apoptosis. Inhibition of caspase-9, an apical caspase in the mitochondrial apoptosis pathway, suppressed oxidative stress-induced apoptosis, whereas inhibition of caspase-8 had no effect, indicating that both the JNK pathway and the mitochondrial apoptosis machinery are central to oxidative stress-induced apoptosis. Both JNK and SEK1 localized on mitochondria where JNK was activated by oxidative stress. Furthermore, active JNK caused the release of apoptogenic factors such as cytochrome c from isolated mitochondria in a cell-free assay. These findings indicate that the JNK pathway is a direct activator of mitochondrial death machinery without other cellular components and provide a molecular linkage from oxidative stress to the mitochondrial apoptosis machinery.

The role of nitric oxide (NO) in microvascular permeability is controversial, in part because the regulation of its endothelial constitutive synthase, eNOS, has been studied in vitro but not in vivo. Our study was designed to detect the morphologic and functional presence of eNOS and to test whether eNOS could be phosphorylated by platelet-activating factor (PAF), an agent that induces hyperpermeability. Immunocytochemistry was applied using human anti-eNOS antibodies in the hamster cheek pouch (hcp). The hcp microvessels demonstrated positive reaction products in the endothelium. The functional presence of eNOS in hcp was investigated by topical application of 10(-7) M PAF to the hcp and by measuring NO production by chemiluminescence. The mean baseline value of NO release was 63.3 +/- 6.9 pmol/ml (mean +/- SE). Application of PAF led to an increase in mean NO release to 120.8 +/- 31.2 pmol/ml (P0.05). In another series of experiments, 10(-7) M PAF was applied topically to hcp preincubated with [(32)P]orthophosphoric acid. Immunoprecipitation and Western blots detected (32)P-labeled bands that migrated with the mobility of positive eNOS indicating phosphorylated eNOS protein. The intensity of the radioactive bands was evaluated by computer-assisted image analysis. Comparison of the net band intensities yielded a mean PAF-treated/control ratio of 1.6 +/- 0.1. Our data demonstrate the morphologic and functional presence of eNOS in the microcirculation. The data also provide evidence that the function of microvascular eNOS is subject to regulation by phosphorylation.

BACKGROUND: The targeting of Ca(2+) cycling has emerged as a potential therapy for the treatment of severe heart failure. These approaches include gene therapy directed at overexpressing sarcoplasmic reticulum (SR) Ca(2+) ATPase, or ablation of phospholamban (PLN) and associated protein phosphatase 1 (PP1) protein complexes. We previously reported that PP1β, one of the PP1 catalytic subunits, predominantly suppresses Ca(2+) uptake in the SR among the three PP1 isoforms, thereby contributing to Ca(2+) downregulation in failing hearts. In the present study, we investigated whether heart-failure-inducible PP1β-inhibition by adeno-associated viral-9 (AAV9) vector mediated gene therapy is beneficial for preventing disease progression in genetic cardiomyopathic mice. METHODS: We created an adeno-associated virus 9 (AAV9) vector encoding PP1β short-hairpin RNA (shRNA) or negative control (NC) shRNA. A heart failure inducible gene expression system was employed using the B-type natriuretic protein (BNP) promoter conjugated to emerald-green fluorescence protein (EmGFP) and the shRNA sequence. AAV9 vectors (AAV9-BNP-EmGFP-PP1βshRNA and AAV9-BNP-EmGFP-NCshRNA) were injected into the tail vein (2×10(11) GC/mouse) of muscle LIM protein deficient mice (MLPKO), followed by serial analysis of echocardiography, hemodynamic measurement, biochemical and histological analysis at 3 months. RESULTS: In the MLPKO mice, BNP promoter activity was shown to be increased by detecting both EmGFP expression and the induced reduction of PP1β by 25% in the myocardium. Inducible PP1βshRNA delivery preferentially ameliorated left ventricular diastolic function and mitigated adverse ventricular remodeling. PLN phosphorylation was significantly augmented in the AAV9-BNP-EmGFP-PP1βshRNA injected hearts compared with the AAV9-BNP-EmGFP-NCshRNA group. Furthermore, BNP production was reduced, and cardiac interstitial fibrosis was abrogated at 3 months. CONCLUSION: Heart failure-inducible molecular targeting of PP1β has potential as a novel therapeutic strategy for heart failure.

Effects of polyoxyethylene (20) sorbitan monooleate (SMOE20) on the acute toxicity of linear alkylbenzenesulfonate (C12LAS) to fish were investigated in red killifish (Orizias latipes) and carp (Cyprinus carpio). By adding polyoxyethylene sorbitan ester to C12LAS solution, the acute toxicity of C12LAS decreased. As a decreasing toxic effect of these nonionic surfactants, the depression of gill damage was histopathologically observed. No significant hematological and blood biochemical differences were observed between two test using a single C12LAS solution and a mixed solution of C 12 LAS SMOE 20 . The addition of SMOE20 to C12LAS decreased the incorporation of C12LAS into blood and each organ except and spleen gall bladder as well as the adsorption of C12LAS to the gill. The farther inward the phenyl position in the alkyl side chain, the lower the adsorption of C12LAS to gill. Since the acute toxicity of LAS phenyl isomers to fish was known to decrease according to the order adsorption, these results suggest that the decreasing toxic effect of SMOE20 on the acute toxicity of C12LAS is due to depression of more toxic C12LAS adsorption on the gill.

C.I. Solvent Red 23, commercial Sudan III, is widely used in cosmetic products. Chemical analyses and guinea pig sensitization tests were carried out to identify its contact allergens. In the Magnusson & Kligman guinea pig maximization test, C.I. Solvent Red 23 showed 20% positive reactions. By conducting chemical analyses with HPLC and GLC, 2-naphthol (82 ppm), azobenzene (48 ppm), Sudan I (570 ppm) and many unknown impurities, as well as the main constituent pigment Sudan III (87%), were found. The chemical structure of one unknown impurity was identified as an isomer of Sudan III. We found that purified Sudan III showed no positive reaction, while the isomer elicited 30% positive reactions, in the same guinea pig test. Furthermore, cross-sensitization with p-phenylenediamine was investigated using the guinea pig test. Animals sensitized with p-phenylenediamine also showed positive elicitation reactions with purified Sudan III. From these results, the contact allergenicity of C.I. Solvent Red 23 is considered to be due to impurities, including the isomer of Sudan III, 1-(o-phenylazophenylazo)-2-naphthol. Positive reactions to Sudan III previously demonstrated in hairdressers are due to cross-sensitivity with p-phenylenediamine.

HLA antisera were fractionated with DEAE cellulose into IgG, IgA, and IgM fractions.Cytotoxic activity was only in the IgG fraction and agglutinating activity was in the IgA and the IgM fractions.

Soluble HLA leukocytic antigens (HLA A2, A9, A10, B40) were sufficiently stable to be detected by the cytotoxicity inhibition test after the storage for more than six months at 10°C or one year at -70°C. The antigenic stability would be advantageous in application for medico-legal practice.

To investigate the quantitative structure-activity relationship (QSARs) for the acute toxicity of fatty acids and their sodium salts to aquatic organisms, red killifish (Oryzias latipes) and gammarus (Hyale plumulosa) were studied upon their sensitivity to a series of the acids and the sodium salts. Studies on red killifish was conducted both under saline and fresh water conditions. Good QSARs of fatty acids were obtained using an zoctanol/water partition coefficient as the single parameter. The log LC50 of fatty acid salts with C8 to C12 carbon chain length was linearly related to a logarithm of the critical micelle concentrations (CMCs).