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71.
Aruoma OI Moncaster JA Walsh DT Gentleman SM Ke B Liang YF Higa T Jen LS 《Free radical research》2003,37(1):91-97
Injection of the glutamate agonist N-methyl-D-aspartate (NMDA) into the vitreous body of rats resulted in severe degeneration of neurons in the retina, with a loss of 81% of ganglion cells and 43% of non-ganglion cells. The cocktail EM-X is a novel antioxidant drink derived from ferment of unpolished rice, papaya and sea-weeds with effective microorganisms (EM-X). In animals treated with an intraperitoneal injection of EM-X, the loss of ganglion cells was reduced to 55% and that of non-ganglion cells to 34% when compared to untreated NMDA-injected retinas. Cell degeneration resulting from NMDA excitotoxicity, is thought to be mediated via oxidative stress mechanisms. The neuroprotective effect of the EM-X in this system is therefore likely to be due, at least in part, to its flavonoids, saponins, vitamin E and ascorbic content. 相似文献
72.
Ichikawa M 《Zoological science》2003,20(6):687-695
When female mice are mated, they form a memory of the pheromonal signal of the male with which they mated. Our research objective was to determine the neural mechanisms underlying learning and memory by employing a convenient model of pheromone-induced olfactory memory (pheromonal memory). Formation of pheromonal memory depends on the association between mating and exposure to pheromones. Synaptic plasticity involving this memory occurs in the accessory olfactory bulb (AOB), depending on vaginocervical stimulation at mating. The vaginocervical stimulation at mating reduces the dendrodendritic feedback inhibition of principal neurons (mitral/tufted (MT) cells) in the AOB and enhances their cell activity. The enhancement of activity induces on these plastic changes in dendrodendritic synapses, which in turn enhance GABA-mediated inhibition of MT cell activity. This "self-inhibition" of MT cells activity in response to pheromonal signals of the partner can disrupt its signals at the AOB thereby preventing the signals from reaching the central brain. The formation and maintenance of pheromonal memory is based on this inhibition mechanism. 相似文献
73.
Compston J 《Hormone research》2003,60(Z3):77-79
Osteoporosis is a common and serious complication of glucocorticoid therapy, resulting in increased risk of fragility fractures. Recent studies indicate that fracture risk is increased even at low doses of glucocorticoids and that this increased risk is seen soon after the commencement of glucocorticoid therapy. Both increased bone resorption and reduced bone formation contribute to bone loss, which affects cortical and cancellous sites. A number of interventions have been shown to prevent glucocorticoid-induced bone loss, although the strongest evidence exists for the bisphosphonates etidronate, alendronate and risedronate. Primary prevention of bone loss should be considered in all high-risk individuals taking oral glucocorticoids for 3 months or more, for example those aged 65 years or over or those with a previous fragility fracture. In other glucocorticoid-treated individuals, the decision to treat should be based on bone densitometry. 相似文献
74.
Lester S. Johnson John F. Presley Juliet C. Park Timothy E. McGraw 《Journal of cellular physiology》1994,158(1):29-38
A mutant Chinese hamster ovary cell line with nonconditional kinetic defects in receptor internalization and recycling was isolated, based on selection for resistance to a transferrin-diphtheria toxin conjugate and screening for aberrant receptor trafficking. The 12-4 cell line internalizes transferrin at ~75% of the parental rate and recyles transferrin back to the cell surface at ~55% of the parental rate. Internalization of low density lipoprotein is also reduced to ~70% of the parental cell rate, demonstrating that the mutant phenotype affects the trafficking of multiple receptors. Characterization of somatic cell hybrids indicated that the 12-4 phenotype is recessive, and complementation analysis determined that the 12-4 cell line is a member of the End2 complementation group. End2 mutants have previously been described as defective in endosomal acidification but have not been known to be defective in receptor trafficking. We have found similar defects in another End2 mutant cell line, suggesting that slowed receptor trafficking is characteristic of End2 mutants. Interestingly, transferrin receptor recycling and internalization are also slowed in another complementation group of mutants, End1, that is also defective in endosomal acidification. This study demonstrates altered receptor trafficking in End1 and End2 cell lines, a novel aspect of the mutant phenotypes. These findings provide evidence, based on a cellular genetic approach, that proper endosome acidification is necessary for maintenance of normal receptor recycling. © 1994 Wiley-Liss, Inc. 相似文献
75.
76.
Gloria Omosa-Manyonyi Juliet Mpendo Eugene Ruzagira William Kilembe Elwyn Chomba Fran?ois Roman Patricia Bourguignon Marguerite Koutsoukos Alix Collard Gerald Voss Dagna Laufer Gwynn Stevens Peter Hayes Lorna Clark Emmanuel Cormier Len Dally Burc Barin Jim Ackland Kristen Syvertsen Devika Zachariah Kamaal Anas Eddy Sayeed Angela Lombardo Jill Gilmour Josephine Cox Patricia Fast Frances Priddy 《PloS one》2015,10(5)
Background
Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN) may lead to a unique immune profile, inducing both strong T-cell and antibody responses.Methods
In a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured.Results
The vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-γ ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration.Conclusion
Co-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses.Trial Registration
ClinicalTrials.gov NCT01264445 相似文献77.
MethodsTo investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet.ResultsRYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance. 相似文献
78.
Haruka Momose Takuo Mizukami Madoka Kuramitsu Kazuya Takizawa Atsuko Masumi Kumiko Araki Keiko Furuhata Kazunari Yamaguchi Isao Hamaguchi 《PloS one》2015,10(4)
We have previously identified 17 biomarker genes which were upregulated by whole virion influenza vaccines, and reported that gene expression profiles of these biomarker genes had a good correlation with conventional animal safety tests checking body weight and leukocyte counts. In this study, we have shown that conventional animal tests showed varied and no dose-dependent results in serially diluted bulk materials of influenza HA vaccines. In contrast, dose dependency was clearly shown in the expression profiles of biomarker genes, demonstrating higher sensitivity of gene expression analysis than the current animal safety tests of influenza vaccines. The introduction of branched DNA based-concurrent expression analysis could simplify the complexity of multiple gene expression approach, and could shorten the test period from 7 days to 3 days. Furthermore, upregulation of 10 genes, Zbp1, Mx2, Irf7, Lgals9, Ifi47, Tapbp, Timp1, Trafd1, Psmb9, and Tap2, was seen upon virosomal-adjuvanted vaccine treatment, indicating that these biomarkers could be useful for the safety control of virosomal-adjuvanted vaccines. In summary, profiling biomarker gene expression could be a useful, rapid, and highly sensitive method of animal safety testing compared with conventional methods, and could be used to evaluate the safety of various types of influenza vaccines, including adjuvanted vaccine. 相似文献
79.
80.
Katrina J. Curtis Katie A. O’Brien Rebecca J. Tanner Juliet I. Polkey Magdalena Minnion Martin Feelisch Michael I. Polkey Lindsay M. Edwards Nicholas S. Hopkinson 《PloS one》2015,10(12)