Visualization of newly deposited tau in neurofibrillary tangles and neuropil threads

Neurofibrillary tangles (NFTs) and neuropil threads (NTs), the major hallmark of Alzheimer disease (AD), are composed of the microtubule-associated protein tau that has undergone posttranslational modifications, including deamidation and isomerization on asparaginyl or aspartyl residues. Because such modifications represent protein aging, we generated 2 antibodies, TM4, specific for Asp-387 of tau, and iD387, specific for isoAsp-387 of tau, to investigate the evolution of NFTs and NTs. On Western blots of Sarkosyl-insoluble fractions, TM4 strongly labeled paired helical filament-tau (PHF-tau), whereas iD387 preferentially labeled PHF smear. Thus, it is reasonable to postulate that TM4-labeled tau (unmodified tau species) represents more recent deposition, and iD387-labeled tau (modified tau species) represents earlier deposition. Unexpectedly, TM4 immunostained even highly evolved NFTs, suggesting that deposition of newly produced tau continues until neuronal death. iD387 labeled the whole profile of NFTs up to distal dendritic branches, whereas TM4 staining was localized to particular portions of NFTs in proximal dendrites and neuronal perikarya. In NTs, TM4 preferentially labeled the outer portion, whereas iD387 intensely labeled the core portion. Based on TM4-positive NFT counts and total NFT counts, we speculate that NFTs in the human hippocampus are produced at a constant rate irrespective of the disease stage.     

Effects of fasting and refeeding on jejunal morphology and cellular activity in rats in relation to depletion of body stores

BACKGROUND: Intestinal mucosa atrophy following a period of starvation characterized by the mobilization of fat stores for energy expenditure (phase II) worsen after a long fast marked by an increase in protein catabolism (phase III). However, the morphology of the jejunum is completely restored after 3 days of refeeding. The aim of this study was to determine the mechanisms involved in the rapid jejunal restoration following the critical phase III. METHODS: Jejunal structure was observed through conventional and environmental scanning electron microscopy, whilst cellular dynamics were studied using classical optic microscopy tools and immunohistochemistry. RESULTS: Mucosal structural atrophy during fasting proved to worsen over the two phases. During phase II, apoptosis is still present at the tip of the villi, the number of mitosis in crypts showed a 30% decrease and a transient drop in cell migration is observed. During phase III, however, an 85% rise in mitosis was noticed along with an increase in cell migration and the disappearance of apoptotic cells at the villus tips. This increased cell renewal continues after food ingestion. CONCLUSIONS: Starved rats appeared to be in a phase of energy sparing in phase II, with depressed cellular events in the intestinal mucosa. In phase III, however, the preservation of functional cells and the early increase in crypt cell proliferation should prepare the mucosa to refeeding and could explain why jejunal repairs are complete after 3 days of refeeding following either phase II or phase III.     

CXCR4 expression in vitreoretinal membranes

BACKGROUND/AIM: Proliferative vitreoretinopathy (PVR) and macular pucker (MP) vitreoretinal membranes are caused by abnormal cell migration. By their role in chemotactism, chemokine receptors represent good candidates to sustain this process. The authors thus investigated the expression of one of them, CXCR4, in these pathologies. METHODS: Three PVR and four MP membranes were surgically removed and processed for immunochemical studies with antibodies for CXCR4, cytokeratins or smooth muscle actin. RESULTS: CXCR4 expression was found in all membranes. There was no relation between severity of PVR or MP and presence of CXCR4. In addition, there was no difference in CXCR4 expression between MP and PVR. CONCLUSION: CXCR4 is expressed in PVR and MP. Further experiments are needed to test if CXCR4 and other chemokine receptors are implicated in vitreoretinal membrane formation.     

Anti-obesity action of Salix matsudana leaves (Part 2). Isolation of anti-obesity effectors from polyphenol fractions of Salix matsudana

Previously, it was reported that polyphenol fractions prepared from the leaves of Salix matsudana reduced the elevation of the rat plasma triacylglycerol level at 3 and 4 h after oral administration of a lipid emulsion containing corn oil, at a dose of 570 mg/kg. Moreover, body weights at 2-9 weeks and the fi nal parametrial adipose tissue weights were significantly lower in mice fed the high-fat diet with 5% polyphenol fractions of S. matsudana leaves than in those fed the high-fat diet alone. The polyphenol fractions of S. matsudana leaves also significantly reduced the hepatic total cholesterol content, which was elevated in mice fed the high-fat diet alone. In addition, the polyphenol fractions of S. matsudana leaves inhibited palmitic acid uptake into brush border membrane vesicles prepared from rat jejunum and alpha-amylase activity, and their fractions enhanced norepinephrine-induced lipolysis in fat cells. To clarify the active substances inhibiting the palmitic acid uptake into small intestinal brush border membrane, the alpha-amylase activity or enhancing the norepinephrine-induced lipolyis in fat cells, the isolation of the active substances from polyphenol fraction was attempted using the above three assay systems. Compounds 1, 2 and 3 were isolated from the polyphenol fractions and identified as apigenin-7-O-d-glucoside, luteolin-7-O-d-glucoside and chrysoeriol-7-O-d-glucoside, respectively. Among three flavonoids, apigenin-7-O-d-glucoside inhibited alpha-amylase activity, and luteolin-7-O-d-glucoside and chrysoeriol-7-O-d-glucoside inhibited palmitic acid uptake into small intestinal brush border membrane. Furthermore, three flavonoid glucosides enhanced norepinephrine-induced lipolysis in fat cells.     

Chorioamnionitis caused by Serratia marcescens in a non-immunocompromised host

A 26 year old pregnant woman with antithrombin III deficiency developed recurrent septicaemia with Serratia marcescens. In spite of the administration of antibiotics, high grade fever persisted. She subsequently manifested lower abdominal pain, and spontaneous abortion occurred. After the abortion, she became completely afebrile. The amnion was turbid, and microscopic examination of the placenta showed haemorrhage and massive infiltration of neutrophils, suggestive of infectious chorioamnionitis. Pulsed field gel electrophoresis showed that isolates from the blood, urine, and vaginal discharge were genetically identical. Intravenous pyelography revealed that she had a bilateral completed double ureter. It was thought that a urinary tract anomaly caused infection with S marcescens, and the pathogen spread to the chorioamnion via the bloodstream. This is the first report of chorioamnionitis caused by S marcescens in a non-immunocompromised host. In addition, these findings indicate that the chorioamnion can serve as a site for persistent infection in normal pregnancies.     

Gender-dependent differences in the incidence of ochratoxin A-induced neural tube defects in the Pdn/Pdn mouse

Genetic polydactyly/arhinencephaly mouse embryo, Pdn/Pdn , exhibits suppression of Gli3 gene expression. Ochratoxin A (OTA) is a teratogen that causes neural tube defects (NTD) in mice. We investigated gender-dependent differences in the incidence of NTD induced by OTA in the Pdn/Pdn mouse. After administering 2 mg/kg OTA to Pdn /+ female mice, mated with Pdn /+ males, on day 7.5 of gestation, we examined the genotypes, sex and NTD of fetuses on day 18. Non-treated Pdn / Pdn had a 15.8% risk of NTD, and all NTD fetuses were female. When Pdn / Pdn embryos were exposed to OTA, the incidence of NTD increased to 16 (51.6%) of 31 Pdn / Pdn fetuses, and 10 (71.4%) of 14 male Pdn / Pdn fetuses exhibited NTD. From these results, it was speculated that NTD in OTA-treated male Pdn / Pdn were due to the synergistic effect between depressed Gli3 and altered sex-correlated gene expression from OTA treatment. After treatment with OTA, the embryos were recovered on day 9 and gene expressions, which were correlated with Gli3 , telencephalic morphogenesis, formation of gonadal anlage, and gender-dependent differentiation were investigated. From real-time polymerase chain reaction analysis results, it was suggested that the manifestation of NTD in the male OTA-treated Pdn/Pdn might be due to the complicated altered gene expressions among Gli3, Wnt7b, Wnt8b , Fez1 , Barx1, Lim1, Dmrt1, Igf1 , Fog2, Dax1 and Sox9, and in particular, upregulation and gender-dependent difference in Barx1 and gender-dependent difference in Sox9 gene expressions might be noteworthy findings.     

Effects of Red Ginseng extract on ultraviolet B-irradiated skin change in C57BL mice

Red Ginseng (the roots of Panax ginseng C.A. Meyer) is used clinically in China, Korea and Japan for various diseases, including atherosclerosis, hypertension and stress etc. Although Red Ginseng roots have traditionally been thought to have antiageing effects, the basis for this hearsay is unclear. This study examined the effects of Red Ginseng extract on ultraviolet B (UVB)-irradiated skin ageing in mice. Oral administration of Red Ginseng extract (20 or 60 mg/kg, twice daily) prevented UVB-irradiated skin damage (increases of skin thickness and pigmentation, and reduction of skin elasticity). Furthermore, Red Ginseng extract inhibited the increases of epidermis and corium thickness induced by UVB irradiation. Red Ginseng extract inhibited the increase of skin TGF-beta1 content induced by UVB irradiation. These findings suggest that the protective action of Red Ginseng extract against UVB-irradiated skin ageing may be due partly to an inhibition of the increase of skin TGF-beta1 induced by UVB irradiation. In conclusion, the oral administration of Red Ginseng extract may be useful as a health supplement for protection against photoageing.     

Using educational games to promote the seeking of a pharmacist and to teach key medication use messages: Results from an inner city health party

BackgroundLow health literacy affects 80–90 million Americans with low-income, minority populations being more vulnerable to this condition. One method of addressing limited literacy that may be particularly well accepted within vulnerable populations is the use of educational board games in order to emphasize seeking health information from reliable sources such as pharmacists.ObjectiveThe research objective was to determine if the use of educational board games could impact community pharmacy patron intentions to seek pharmacist advice in an urban, minority, economically-disadvantaged population.MethodsFour medication-related educational games were played at an urban community pharmacy under the leadership of pharmacy students in the setting of a health party. Game messages, design, and evaluation processes were uniquely guided by community members' input. A verbally administered questionnaire measured game impact via knowledge and perception questions with responses compared between a non-randomly allocated intervention group and a control group.ResultsNinety-nine adults were included in the intervention (or game) group and 94 adults were in the control group. Game participants were significantly more likely than the control group to indicate they would seek pharmacist medication advice in the future.ConclusionEducational board games played in the setting of a health party can be a fun and effective way to convey selected health messages within an urban, minority, economically disadvantaged population. Community input into game development and layering multiple strategies for overcoming health literacy barriers were essential components of this initiative.     

In Vivo and In Vitro Treatment With Edaravone Promotes Proliferation of Neural Progenitor Cells Generated Following Neuronal Loss in the Mouse Dentate Gyrus

Edaravone is clinically used in Japan for treatment of patients with acute cerebral infarction. To clarify the effect of edaravone on neurogenesis in the hippocampus following neuronal injury in the hippocampal dentate gyrus, we investigated the effect of in vitro and in vivo treatment with edaravone on the proliferation of neural stem/progenitor cells prepared from the mouse dentate gyrus damaged by trimethyltin (TMT). Histological assessment revealed the presence of large number of nestin(+) cells in the dentate gyrus on days 3 – 5 post-TMT treatment. We prepared cells from the dentate gyrus of naïve, TMT-treated mice or TMT/edaravone-treated mice. The cells obtained from the dentate gyrus of TMT-treated animals were capable of BrdU incorporation and neurosphere formation when cultured in the presence of growth factors. The TMT-treated group had a larger number of nestin(+) cells and nestin(+)GFAP(+) cells than the naïve one. Under the culture condition used, sustained exposure of the cells from the damaged dentate gyrus to edaravone at 10^?11 and 10^?8 M promoted the proliferation of nestin(+) cells. The systemic in vivo treatment with edaravone for 2 days produced a significant increase in the number of nestin(+) cells among the cells prepared from the dentate gyrus on day 4 post-TMT treatment, and as well as one in the number of neurospheres formed from these cells in the culture. Taken together, our data indicated that edaravone had the ability to promote the proliferation of neural stem/progenitor cells generated following neuronal damage in the dentate gyrus.     

Antitumor actions of a chromone glucoside cnidimoside A isolated from <Emphasis Type="Italic">Cnidium japonicum</Emphasis>

In a series of studies on the search for new antitumor and antimetastatic substances from the natural medicinal plants of the Umbelliferae family, we previously reported that chalcone derivatives isolated from Angelica keisekei roots have antitumor and antimetastatic activities. In the present study, we examined the effects of a chromone glucoside cnidimoside A isolated from Cnidium japonicum whole plants on tumor growth and tumor metastasis in colon 26-bearing mice. Cnidimoside A (50 mg/kg, twice daily) significantly inhibited tumor growth and final tumor weight compared to the growth in vehicle-treated colon 26-bearing mice (control). Furthermore, the number of mice with abdominal invasion of tumors was also reduced by orally administered cnidimoside A (50 mg/kg, twice daily). In this study, the CD8⁺ T Cell- and interferon (IFN)-γ-positive cell numbers in the small intestine in the colon 26-bearing mice were significantly reduced compared with those in the normal mice, but the natural killer (NK)-positive cell number did not differ significantly between the normal and colon 26-bearing mice. The CD8⁺ T-, NK and IFN-γ-positive cell numbers in the small intestine were significantly increased by orally administered cnidimoside A (50 mg/kg, twice daily) compared to those in vehicle-treated colon 26-bearing mice. In conclusion, it seems likely that the antitumor and antimetastatic actions of cnidimoside A may be partly associated with the stimulation of immune response in the small intestine.