Involvement of the Thalamus, Hippocampus, and Brainstem in Hypsarrhythmia of West Syndrome: Simultaneous Recordings of Electroencephalography and fMRI Study.

BACKGROUND AND PURPOSE: West syndrome is a developmental and epileptic encephalopathy characterized by epileptic spasms, neurodevelopmental regression, and a specific EEG pattern called hypsarrhythmia. Our aim was to investigate the brain activities related to hypsarrhythmia at onset and focal epileptiform discharges in the remote period in children with West syndrome using simultaneous electroencephalography and fMRI recordings. MATERIALS AND METHODS: Fourteen children with West syndrome underwent simultaneous electroencephalography and fMRI at the onset of West syndrome. Statistically significant blood oxygen level-dependent responses related to hypsarrhythmia were analyzed using an event-related design of 4 hemodynamic response functions with peaks at 3, 5, 7, and 9 seconds after the onset of each event. Six of 14 children had focal epileptiform discharges after treatment and underwent simultaneous electroencephalography and fMRI from 12 to 25 months of age. RESULTS: At onset, positive blood oxygen level-dependent responses were seen in the brainstem (14/14 patients), thalami (13/14), basal ganglia (13/14), and hippocampi (13/14), in addition to multiple cerebral cortices. Group analysis using hemodynamic response functions with peaks at 3, 5, and 7 seconds showed positive blood oxygen level-dependent responses in the brainstem, thalamus, and hippocampus, while positive blood oxygen level-dependent responses in multiple cerebral cortices were seen using hemodynamic response functions with peaks at 5 and 7 seconds. In the remote period, 3 of 6 children had focal epileptiform discharge-related positive blood oxygen level-dependent responses in the thalamus, hippocampus, and brainstem. CONCLUSIONS: Positive blood oxygen level-dependent responses with hypsarrhythmia appeared in the brainstem, thalamus, and hippocampus on earlier hemodynamic response functions than the cerebral cortices, suggesting the propagation of epileptogenic activities from the deep brain structures to the neocortices. Activation of the hippocampus, thalamus, and brainstem was still seen in half of the patients with focal epileptiform discharges after adrenocorticotropic hormone therapy.

Inhibitory effects of Sanguisorba officinalis root extract on HYBID (KIAA1199)-mediated hyaluronan degradation and skin wrinkling.

OBJECTIVES: Hyaluronan (HA), an important constituent of extracellular matrix in the skin, has many biological activities such as hydration that contributes to firmness and bounciness of the skin. We have reported that reduction in HA in the papillary dermis and over-expression of HYBID (HYaluronan Binding protein Involved in hyaluronan Depolymerization, alias KIAA1199 or CEMIP), a key molecule for HA degradation in skin fibroblasts, are implicated in facial skin wrinkling in Japanese and Caucasian women. However, little or no information is available for substances which inhibit the HYBID-mediated HA degradation. METHODS: Inhibition of Sanguisorba officinalis root extract and ziyuglycoside I, one of the components of Sanguisorba officinalis root extract, to the HYBID-mediated HA degradation was assessed by size-exclusion chromatography of HA depolymerized by stable transfectants of HYBID in HEK293 cells (HYBID/HEK293 cells) or normal human skin fibroblasts (Detroit 551 cells and NHDF-Ad cells). The HYBID mRNA and protein expression was examined by quantitative real-time PCR and immunoblotting in the skin fibroblasts treated with Sanguisorba officinalis root extract, and size distribution of newly produced HA was evaluated by preparing metabolically radiolabelled HA. A double-blind, randomized and placebo-controlled study was carried out in the 21 healthy Japanese women, who were topically treated with the formulation containing Sanguisorba officinalis root extract or the placebo on each side of the face including crow's foot area. RESULTS: Sanguisorba officinalis root extract, but not ziyuglycoside I, abolished HYBID-mediated HA degradation by HYBID/HEK293 cells. Sanguisorba officinalis root extract also inhibited HYBID-mediated HA degradation in skin fibroblasts by down-regulating HYBID mRNA and protein expression. Although control untreated skin fibroblasts produced polydispersed HA, the cells treated with Sanguisorba officinalis root extract produced only high-molecular-weight HA. Treatment with Sanguisorba officinalis root extract-formulated lotion significantly improved skin elasticity, and reduced skin wrinkling scores at the outer eye corner compared with the placebo formulation. CONCLUSION: Sanguisorba officinalis root extract showed an anti-HYBID-mediated HA degradation activity and anti-wrinkle activity on human facial skin, which is accompanied by the improvement in elasticity. Our study provides the possibility of a new strategy to inhibit HYBID-mediated HA degradation for anti-wrinkle care.

OBJECTIFS: l'acide hyaluronique (AH), un composant important de la matrice extracellulaire de la peau, assure de nombreuses activités biologiques, telles que l'hydratation qui contribue à la fermeté et l'élasticité de la peau. Nous avons rapporté que la réduction d'AH dans le derme papillaire et une surexpression de la protéine de liaison de l'AH impliquée dans la dépolymérisation de l'AH (HYBID, alias KIAA1199 ou CEMIP), une molécule clé de la dégradation de l'AH des fibroblastes cutanés, sont impliquées dans la formation des rides au niveau de la peau du visage chez les femmes d'origine japonaise et caucasienne. Cependant, peu ou aucune information n'est disponible concernant les substances qui inhibent la dégradation de l'AH provoquée par la protéine HYBID. MÉTHODES: l'inhibition de l'extrait de racine de la pimprenelle (Sanguisorba officinalis) et du ziyuglycoside I, l'un des composants de l'extrait de racine de Sanguisorba officinalis, sur la dégradation de l'AH provoquée par la protéine HYBID a été évaluée à l'aide d'une chromatographie par exclusion stérique de l'AH dépolymérisé par des transfectants stables de la protéine HYBID dans les cellules HEK293 (cellules HYBID/HEK293) ou les fibroblastes cutanés humains normaux (lignée cellulaire Detroit 551 et cellules des fibroblastes du derme humain chez l'adulte). L'expression de l'ARNm et de la protéine HYBID a été examinée par PCR quantitative en temps réel et par immuno-empreinte des fibroblastes cutanés traités avec de l'extrait de racine de Sanguisorba officinalis, et l'attribution des tailles des nouveaux échantillons produits de l'AH a été évaluée par préparation d'AH radiomarqué métaboliquement. Une étude en double aveugle, randomisée et contrôlée par placebo a été menée auprès des 21 femmes japonaises en bonne santé, qui ont été traitées localement avec la formulation élaborée à partir d'extraits de racine de Sanguisorba officinalis ou un placebo, sur chaque côté du visage, notamment sur la zone à pattes d'oie. RÉSULTATS: l'extrait de racine de Sanguisorba officinalis a permis d'arrêter la dégradation de l'AH provoquée par la protéine HYBID par les cellules HYBID/HEK293, mais ce n'était pas le cas du ziyuglycoside I. L'extrait de racine de Sanguisorba officinalis a également inhibé la dégradation de l'AH provoquée par la protéine HYBID des fibroblastes cutanés en diminuant l'expression de l'ARNm et des protéines HYBID. Bien que les fibroblastes cutanés témoins non traités aient produit de l'AH polydispersé, les cellules traitées aux extraits de racine de Sanguisorba officinalis ont produit uniquement de l'AH de haut poids moléculaire. Le traitement par lotion formulée à partir d'extraits de racine de Sanguisorba officinalis a amélioré de manière significative l'élasticité de la peau et réduit les scores de vieillissement du coin extérieur de la peau autour des yeux, par rapport à la formulation placebo. CONCLUSION: l'extrait de racine de Sanguisorba officinalis a démontré une action anti-dégradation de l'AH provoquée par la protéine HYBID et une activité antirides au niveau de la peau du visage humain, s'accompagnant d'une amélioration de l'élasticité. Notre étude fournit la possibilité d'une nouvelle stratégie pour inhiber la dégradation de l'AH provoquée par la protéine HYBID dans le cadre des soins antirides.

Relationship between the phenylephrine test and eyelid droop after aponeurotic repair with the use of an epinephrine-containing local anaesthetic.

PurposeTo analyse the relationship between the results of the phenylephrine test and postoperative eyelid droop in transcutaneous aponeurotic repair using epinephrine-containing local anaesthetic for aponeurotic blepharoptosis.Patients and methodsWe retrospectively reviewed the medical records of 66 eyelids from 40 patients who underwent transcutaneous aponeurotic repair. A positive phenylephrine test result was defined as an increase in margin reflex distance-1 (MRD-1) ≥0.5 mm after application of phenylephrine eye drops. The patients were divided into a positive phenylephrine response group (Group A, 16 patients) and a negative phenylephrine response group (Group B, 24 patients). The ΔMRD-1 was calculated by subtracting the 3-month postoperative value from the intraoperative value. Patient age, sex, pre- and intraoperative MRD-1s, levator function, and phenylephrine response were investigated as factors potentially influencing the ΔMRD-1. The relationship between these factors and ΔMRD-1 was analysed using single and multiple regression analysis.ResultsThe ΔMRD-1 in Group A (0.68±0.52 mm) was significantly greater than that in Group B (0.17±0.56 mm; P=0.004). A moderate correlation was found between phenylephrine response and ΔMRD-1 in the total patient group (YΔMRD-1=0.441 Xphenylephrine+0.358; r=0.462; r2=0.213; P=0.002).ConclusionsAlthough the ΔMRD-1 in Group B was quite small, the ΔMRD-1 in Group A was considerable, and there was a moderate positive correlation between phenylephrine response and the ΔMRD-1 overall. This indicates that the degree of postoperative eyelid droop can be estimated by the phenylephrine test results in transcutaneous aponeurotic repair.

Safety of UFT/LV and S-1 as adjuvant therapy for stage III colon cancer in phase III trial: ACTS-CC trial.

BACKGROUND: The Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) is a phase III trial designed to validate the non-inferiority of S-1 to UFT/leucovorin (LV) as postoperative adjuvant chemotherapy for stage III colon cancer. We report the results of a planned safety analysis. METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive UFT/LV (UFT, 300 mg m(-2) per day as tegafur; LV, 75 mg per day on days 1-28, every 35 days, 5 courses) or S-1 (80, 100, or 120 mg per day on days 1-28, every 42 days, 4 courses). Treatment status and safety were evaluated. RESULTS: Of 1535 enrolled patients, a total of 1504 (756 allocated to S-1 and 748 to UFT/LV) were analysed. The completion rate of protocol treatment was 77% in the S-1 group and 73% in the UFT/LV group. The overall incidence of adverse events (AEs) were 80% in S-1 and 74% in UFT/LV. Stomatitis, anorexia, hyperpigmentation, and haematological toxicities were common in S-1, whereas increased alanine aminotransferase and aspartate aminotransferase were common in UFT/LV. The incidences of grade 3 AEs were 16% and 14%, respectively. CONCLUSION: Although AE profiles differed between the groups, feasibility of the protocol treatment was good. Both S-1 and UFT/LV could be safely used as adjuvant chemotherapy.

Supplementation of the diet of dairy cows with trehalose results in milk with low lipid peroxide and high antioxidant content.

The objective of this study was to investigate the effect of dietary supplementation with the disaccharides trehalose and cellobiose on antioxidant activity in rumen fluid, blood, and milk of dairy cows. Nine Holstein dairy cows housed in a free-stall barn were divided into 3 groups, with each group receiving a different dietary treatment (a control diet, a 1% trehalose-supplemented diet, or a 1% cellobiose-supplemented diet) following a 3x3 Latin square design. Feed intake and milk production increased in cows receiving the trehalose-supplemented diet compared with those receiving the control and cellobiose-supplemented diets. The total protozoa numbers in the rumen fluid of cows fed trehalose- or cellobiose-supplemented diets were greater than those of the control group. The C18:0 and C18:1 fatty acid content was increased in the milk of cows fed the trehalose-supplemented diet compared with that of the control group, and the C18:3n-3 fatty acid content in the milk of cows fed the cellobiose-supplemented diet was less than that of the control group. Plasma biochemical parameters were unchanged among the different treatments. In rumen fluid, 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and superoxide dismutase activity were increased 2h after feeding in cows receiving the cellobiose-supplemented diet compared with the control group, and the concentration of thiobarbituric acid reactive substances in the rumen fluid of cows fed the cellobiose-supplemented diet was decreased. In contrast, the values of these parameters measured in the milk of cows fed the cellobiose-supplemented diet were no different from those of control cows. Dietary supplementation with trehalose did, however, bring about an improvement of the oxidative status of milk and blood in these animals compared with controls. These results provide the first evidence supporting the use of dietary disaccharides to decrease lipid peroxide levels and increase the antioxidant content of dairy cow milk. The findings suggest that disaccharides, particularly trehalose, might be useful as supplements for reducing oxidative stress and improving the quality of milk for human consumption, as well as possibly impairing the processes that give rise to lipid oxidation odor in dairy cow milk.

Two routes for pollen entering indoors: ventilation and clothes.

BACKGROUND: The route by which pollen enters dwellings has not been clarified. OBJECTIVE: To evaluate the amount of pollen entering dwellings by ventilation and adhesion to textile products. METHODS: The amount of pollen clinging to fabrics (clothes, laundry, and futon bedding) out of doors was measured by quantification of Japanese cedar pollen antigen Cry j 1. The effect of air ventilation on the amount of pollen indoors was also investigated using several neighboring unoccupied apartments with an identical layout while controlling the ventilation conditions. RESULTS: The amount of pollen adhering to futons was especially high. More than half of the pollen on futons or laundry remained on the surface, even after being brushed off by hand or shaken off. Vacuuming laundry and futons after airing out would be an effective way to decrease the amount of indoor pollen. A large amount of pollen entered dwellings through air ducts when the windows were closed and the ventilation fans working. Since most pollen that entered by ventilation remained near the windows, cleaning carefully and frequently near windows could reduce the amount of pollen indoors. CONCLUSIONS: To decrease the amount of pollen indoors, special attention must be paid to textile products and ventilation systems during the pollen season.

Formulation and evaluation of lactoferrin bioadhesive tablets.

For the treatment of chronic inflammation in the oral cavity, we attempted to develop bioadhesive tablets of bovine lactoferrin (B-LF) which has antibacterial properties and immune regulatory functions. B-LF tablets containing pectin, tamarind gum or carboxymethylcellulose (CMC) were prepared by direct compression. Tablets consisting of B-LF, pectin and xylitol passed through 60- or 100-mesh sieves were also prepared. The tablets containing CMC had insufficient bioadhesive force. Although the tablets containing tamarind gum showed the longest residence time in the oral cavity, an unpleasant taste gradually developed. The tablets containing pectin showed the highest value of bioadhesive force and the taste was acceptable. The characteristics of the B-LF tablets were improved by adding an appropriate amount of xylitol and using the ingredients sieved by a 100-mesh sieve. The therapeutic effect was evaluated by using rats with an ulcer on the oral mucosa. In the present study, swelling on the periphery of the ulcer was observed after administration of the B-LF tablets, and then the ulcer has reduced overall.

Fat-tailed gene flow in the dioecious canopy tree species Fraxinus mandshurica var. japonica revealed by microsatellites.

Pollen flow, seed dispersal and individual reproductive success can be simultaneously estimated from the genotypes of adults and offspring using stochastic models. Using four polymorphic microsatellite loci, gene flow of the wind-pollinated and wind-seed-dispersed dioecious tree species, Fraxinus mandshurica var. japonica, was quantified in a riparian forest, in northern Japan. In a 10.5-ha plot, 74 female adults, 76 male adults and 292 current-year seedlings were mapped and genotyped, together with 200 seeds. To estimate dispersal kernels of pollen and seeds, we applied normal, exponential power, Weibull, bivariate t-distribution kernels, and two-component models consisting of two normal distribution functions, one with a small and one with a large variance. A two-component pollen flow model with a small contribution (26.1%) from short-distance dispersal (sigma = 7.2 m), and the rest from long-distance flow (sigma = 209.9 m), was chosen for the best-fitting model. The average distance that integrated pollen flows inside and outside the study plot was estimated to be 196.8 m. Tree size and flowering intensity affected reproduction, and there appeared to be critical values that distinguished reproductively successful and unsuccessful adults. In contrast, the gene flow model that estimated both pollen and seed dispersal from established seedlings resulted in extensive seed dispersal, and the expected spatial genetic structures did not satisfactorily fit with the observations, even for the selected model. Our results advanced small-scale individual-based parentage analysis for quantifying fat-tailed gene flow in wind-mediated species, but also clarified its limitations and suggested future possibilities for gene flow studies.

[Successful off-pump coronary artery bypass for a patient with aplastic anemia].

We report a 61-year-old man with aplastic anemia who underwent successful off-pump coronary artery bypass (OPCAB) after being admitted for angina pectoris. Coronary angiography showed severe stenosis of the left main coronary artery. Preoperative WBC was 2,200/microl, neutrophil 704/microl, Hb 8.1g/dl, and PLT 16,000/microl. We conducted OPCAB on double vessels using left internal thoracic and radial artery grafts. Thirty units of platelets were transfused intraoperatively with little perioperaive hemorrhage. Because of high grade fever, we injected 150 microg granulocyte colony-stimulating factor (G-CSF) every 3 days postoperatively to prevent major infection. The combination of appropriate perioperative management and OPCAB yielded an effective result for a patient with severe hematological disorders causing pancytopenia.

Design and construction of resonant cavity applicator for brain tumor hyperthermia treatment without contact.

A re-entrant type resonant cavity applicator for brain tumor hyperthermia treatment is presented. In this method, a human brain is placed between the gap of the inner re-entrant cylinders without contact. This cavity has a window for insertion of the human head. Here, first, to design and construct a resonant cavity applicator, the results of the temperature distribution inside an agar phantom and electromagnetic field leaked from the attached window to the environment by the computer simulation were presented. Second, The developed resonant cavity and inner electrode, which were made of an aluminum alloy, were presented. Third, the experimental heating result of the agar phantom was presented. In the experiment, the center region of the agar phantom is heated to 42 degrees C. The leaked electric field strength at the position of 10 cm away from the center of the window was less than that of 10% of the center of the agar phantom. It was found that the developed resonant cavity applicator was applicable to both deep and regional brain hyperthermia treatment.

Influence of low-frequency massage device on transdermal absorption of ionic materials.

The influence of a low-frequency massage device on transdermal absorption of sodium benzoate, ketoprofen and diclofenac sodium was investigated in rats. Electrode pads spread with a hydroxypropyl cellulose gel containing the drug model were placed on excised skin in vitro. The transdermal permeation studies were carried out in the treatment group with the pulse applied through electrode pads spread with the gel, the pretreatment group with the gel applied after the application of the pulse and in the control group in which the gel was applied without the pulse. In vivo, transdermal absorption of ketoprofen was examined in the same groups used for the in vitro study. The pharmacokinetics of ketoprofen in plasma after intravenous injection was also studied. The treatment group showed higher cumulative permeated amounts of the drug models than the control in vitro. However, the enhancing effect was not observed in the pretreatment group. In vivo, the plasma ketoprofen level increased temporarily after the pulse was applied and then increased gradually as compared with the control. Since the distribution of ketoprofen from the central to the peripheral compartment was enhanced by the pulse in the injection study, enhancement of the biodistribution of ketoprofen by the low-frequency pulse was suggested.

Molecular characterization of a 10-kDa buckwheat molecule reactive to allergic patients' IgE.

BACKGROUND: Using the sera from buckwheat (BW)-allergic patients, several putative causative molecules were reported. However, few molecules were determined on the molecular structure. We demonstrated in 2000 that the major allergen with 24 kDa (BW24KD) is a legumin-like storage protein. OBJECTIVE: The aim of this study was to isolate and characterize further a major allergen with 10 kDa by molecular cloning. METHODS AND RESULTS: Buckwheat allergens were identified by immunoblotting analysis using sera from 14 allergic and two nonallergic individuals. We identified a protein with 10 kDa (BW10KD) that reacted with immunoglobulin E (IgE) more strongly than with IgG and IgA in 57% of the allergic patients but not with IgE in nonallergic individuals. Analyses were performed by N-terminal amino acid sequencing and molecular cloning. Physiological significance was assessed by an immunoblotting experiment showing that the reactivity of an allergic patient's serum IgE to BW10KD was competitively inhibited by natural BW extracts. CONCLUSION: Molecular cloning experiments indicated that BW10KD as a BW allergen was a member of the 2S-albumin multigene family.

Manipulated mouse embryos as bioassay system for water quality control.

Mouse pronuclear stage embryos with intact slit zona pellucida (manipulated) were cultured in vitro until the hatched blastocyst stage in simplex optimized medium with higher K+ concentration (KSOM) prepared with three different water types: tap, deionized reverse osmosis (D-O) water and Milli-Q system (M-Q) water. The culture media were supplemented with or without protein and ethylenediaminetetraacetic acid (EDTA, disodium salt). The rates of hatched blastocysts were significantly affected (p < 0.01) by micromanipulation, protein supplement and water source. The water source has no influence (p > 0.05) on development in EDTA-supplemented protein-free culture media, whereas in EDTA- and protein-free culture media, the water quality significantly (p < 0.001) affected the rates of development, with higher rates in media prepared with M-Q water. The micromanipulated embryos showed higher sensitivity to the water quality (p < 0.01). It worth mentioning that the rates of hatched blastocysts in protein-free culture media were very low (0-7.5%). Furthermore, the three different water types were analysed by measuring the electrical conductivity, inorganic ions, total organic carbon and endotoxins to evaluate the purity. M-Q water showed the lowest levels of inorganic ion, total organic carbon and endotoxin concentrations. We concluded that manipulated mouse embryos are good system to evaluate the quality of water used in biological system.

Successful treatment of chromomycosis using carbon dioxide laser associated with topical heat applications.

A 59-year-old Japanese man presented with a slightly elevated, pruritic, erythematous plaque on his left buttock measuring 5 x 5 cm in diameter. The man had a history of chromomycosis, dating 6 years prior to the current consultation, for which he had been treated with oral terbinafine. Diagnosis of a recurrence of chromomycosis of the skin due to infection by Foncecaea pedrosoi was made after careful analysis of the clinical features, skin biopsy, KOH mounts, and fungal culture results. We administered topical heat therapy followed by treatment with CO2 laser to eradicate the unresponsive remnants of the lesion. The operative site re-epithelized within 10 weeks, and 1 year after the treatment there was no evidence of recurrence. For a recalcitrant case of chromomycosis, as in this case, the use of CO2 laser combined with topical heat therapy may be a new therapeutic modality.

Transduction of thymidine phosphorylase cDNA facilitates efficacy of cytosine deaminase/5-FC gene therapy for malignant brain tumor.

The in vivo gene delivery of E. coli cytosine deaminase (cd) cDNA and systemic 5-fluorocytosine (5-FC) administration have been studied extensively because of their clinical relevance to cancer gene therapy. This approach has the potent advantage of a stronger bystander effect compared to the previous thymidine kinase suicide gene system of the herpes simplex virus. However, 5-fluorouracil (5-FU), an active metabolite in cd with 5-FC therapy, is not always effective for every type of tumor since the enzymes responsible for further drug metabolism vary significantly in each tissue. In this study, we aimed to increase the sensitivity of 5-FU by transduction of thymidine phosphorylase (dThdPase) cDNA into brain tumor cells. After retroviral transfer of the cDNA, we obtained 9L murine gliosarcoma cells showing stable expression of the target enzyme (9L-dThdPase). The growth of the cells was identical to wild type (9L-WT) or control-vector transfected (9L-Neo) cells in vitro. Sensitivity to 5-FU was increased in 9L-dThdPase cells. After the adenoviral delivery of cytosine deaminase gene into these cells, 9L-dThdPase cells also demonstrated an increased sensitivity to 5-FC. Moreover, we showed that transduction of dThdPase cDNA prolongs the survival of animals bearing intracerebral tumors after experimental in vivo cytosine deaminase gene therapy. These results suggest that transduction of thymidine phosphorylase may be a beneficial approach to increasing the efficacy of cd/5-FC suicide gene therapy in certain types of tumor.

Dietary mold oil rich in gamma linolenic acid increases insulin-dependent glucose utilization in isolated rat adipocytes.

Effects of dietary fats differing in fatty acid composition on insulin-stimulated glucose metabolism in adipocytes isolated from rat white adipose tissue were compared. Rats were fed experimental diets containing various fats differing in fatty acid composition for 7 days. In the first experiment, rats were fed palm oil mainly consisting of palmitic (45.3%) and oleic acids (39.1%) or safflower oil rich in linoleic acid (71.6%). In the second trial, rats were fed palm oil, or a fat mixture rich in linoleic acid or mold oil rich in gamma-linolenic acid. Contents of fatty acids except for linoleic and gamma-linolenic acid were comparable between the fat mixture and mold oil. The former was devoid of gamma-linolenic acid and contained 42.0% linoleic acid, while the latter contained 25.9% gamma-linolenic and 15.7% linoleic acids. In the first experiment, the insulin-dependent increase in glucose oxidation and incorporation into lipids was higher in rats fed safflower oil compared to those fed palm oil. In the second experiment, the insulin-dependent increase in glucose oxidation and incorporation into lipids was higher in rats fed the fat mixture and mold oil than in those fed palm oil. However, the extent of the increase in these parameters was much greater in rats fed mold oil than in those fed the fat mixture. Therefore, dietary gamma-linolenic acid compared to linoleic acid increases glucose metabolism in response to insulin stimuli in isolated rat adipocytes.

Low density lipoprotein receptor-related protein is required for macrophage-mediated oxidation of low density lipoprotein by 12/15-lipoxygenase.

The oxidative modification of low density lipoprotein (LDL) has been implicated in the early stage of atherosclerosis through multiple potential pathways, and 12/15-lipoxygenase is suggested to be involved in this oxidation process. We demonstrated previously that the 12/15-lipoxygenase overexpressed in mouse macrophage-like J774A.1 cells was required for the cell-mediated LDL oxidation. However, the mechanism of the oxidation of extracellular LDL by the intracellular 12/15-lipoxygenase has not yet been elucidated. In the present study, we found that not only the LDL receptor but also LDL receptor-related protein (LRP), both of which are cell surface native LDL-binding receptors, were down-regulated by the preincubation of the cells with cholesterol or LDL and up-regulated by lipoprotein-deficient serum. Moreover, 12/15-lipoxygenase-expressing cell-mediated LDL oxidation was decreased by the preincubation of the cells with LDL or cholesterol and increased by the preincubation with lipoprotein-deficient serum. Heparin-binding protein 44, an antagonist of the LDL receptor family, also suppressed the cell-mediated LDL oxidation in a dose-dependent manner. The cell-mediated LDL oxidation was dose-dependently blocked by an anti-LRP antibody but not by an anti-LDL receptor antibody. Furthermore, antisense oligodeoxyribonucleotides against LRP reduced the cell-mediated LDL oxidation under the conditions in which the expression of LRP was decreased. The results taken together indicate that LRP was involved essentially for the cell-mediated LDL oxidation by 12/15-lipoxygenase expressed in J774A.1 cells, suggesting an important pathophysiological role of this receptor-enzyme system as the initial trigger of the progression of atherosclerosis.

Flexural strength of a glass-infiltrated alumina dental ceramic incorporated with silicon carbide whiskers.

PURPOSE: The addition of silicon carbide whiskers has been known to reinforce ceramics. This study compared the flexural strength of a glass-infiltrated alumina dental ceramic with various amounts of silicon carbide whiskers incorporated into the alumina matrix. MATERIALS AND METHODS: Three groups with a total of 30 specimens were included: glass-infiltrated alumina dental ceramic with 0, 0.125, and 0.25 wt% silicon carbide whiskers. The flexural strength was measured using a three-point bending test, and the data were analyzed with one-way analysis of variance. Scanning electron microscopy was used to examine the fracture surfaces of all three materials. RESULTS: There were no significant differences in the flexural strength among the three groups. Glass-infiltrated alumina dental ceramic failed predominantly by transgranular fracture and to a lesser degree by intergranular fracture. CONCLUSION: The addition of silicon carbide whiskers did not change the flexural strength of glass-infiltrated alumina dental ceramic.

In vivo selection of Pseudomonas Aeruginosa with decreased susceptibilities to fluoroquinolones during fluoroquinolone treatment of urinary tract infection.

OBJECTIVES: To present a case of fluoroquinolone treatment failure in urinary tract infection caused by Pseudomonas aeruginosa, accompanied by in vivo selection of the post-treatment isolate that showed decreased susceptibilities to fluoroquinolones, and to report fluoroquinolone resistance mechanisms in the post-treatment isolate. METHODS: A patient with urinary tract infection was treated with a suboptimal dose of a fluorinated quinolone, gatifloxacin. P. aeruginosa strains were isolated before and after fluoroquinolone treatment. The pretreatment and post-treatment isolates were examined for relatedness by arbitrarily primed polymerase chain reaction. For these isolates, the minimum inhibitory concentration of antimicrobial agents was determined and mutations in the target genes (gyrA and parC) and regulatory genes (mexR and nfxB) for drug efflux pumps were analyzed. RESULTS: Failure of fluoroquinolone treatment of urinary tract infection was observed. The post-treatment isolate, which was assumed to be isogenic to the pretreatment isolate, exhibited fourfold to 16-fold increases in the MIC of fluoroquinolones. In this isolate, a new mutation, not observed in the pretreatment isolate, was found only in the gyrA gene, resulting in an amino acid change of aspartic acid to asparagine in codon 87 of GyrA. CONCLUSIONS: The P. aeruginosa isolate that was initially susceptible to fluoroquinolones showed decreased susceptibility to fluoroquinolones after treatment with a suboptimal dose of one fluoroquinolone. In the post-treatment isolate, the alteration of GyrA would be responsible for the decreased susceptibility to fluoroquinolones. We should be aware that inappropriate use of fluoroquinolones could select such a strain harboring a quinolone resistance-associated alteration of DNA gyrase.