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Effects of the Phosphatase Inhibitors Calyculin A and Okadaic Acid on Acetylcholine Synthesis and Content of Rat Hippocampal Formation 总被引:2,自引:2,他引:0
Abstract: The biochemical mechanisms involved in the regulation of acetylcholine (ACh) turnover are poorly understood. In the experiments reported here, we examined whether inhibition of the serine/threonine phosphatases 1 and 2A by calyculin A or okadaic acid alters ACh synthesis by rat hippocampal preparations. With hippocampal slices, calyculin A (50 n M ) and okadaic acid (50 n M ) reduced significantly ( p < 0.01) the synthesis of [3 H]ACh from [3 H]choline. Both calyculin A and okadaic acid produced significant depletion of endogenous tissue ACh in a concentration-dependent manner ( p < 0.01). This depletion was not the result of a drug-induced increase of spontaneous ACh release, which was not changed significantly ( p > 0.7) by either drug. Choline acetyltransferase (ChAT) activity from tissue exposed to calyculin A or okadaic acid was reduced in a concentration-dependent manner ( p < 0.05), but these phosphatase inhibitors did not act directly on ChAT in vitro; i.e., enzymatic activity was not altered significantly ( p > 0.4) in the presence of calyculin A or okadaic acid. Both high-affinity and low-affinity [3 H]choline uptake by hippocampal synaptosomes were reduced significantly in a concentration-dependent manner in the presence of calyculin A or okadaic acid; these agents reduced V max values for high- and low-affinity choline uptake ( p < 0.01) with no significant change in K m values ( p > 0.1), indicating a noncompetitive inhibition. Taken together, these data suggest that phosphatase activity plays a role in presynaptic central cholinergic nerve terminal function, in particular in the modulation of ACh synthesis. 相似文献
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Ulf Dittmer Wolfgang Lüke Christiane Stahl-Hennig Cheick Coulibaly Harald Petry Walter Bodemer Gerhard Hunsmann Gerald Voss 《Journal of medical primatology》1994,23(5):298-303
Both naive and vaccinated macaques acquired a virus-specific proliferative helper T-cell reactivity in response to infection with the nonpathogenic human immunodeficiency virus type 2 (HIV-2). In contrast, macaques infected with the pathogenic simian immunodeficiency virus of the macaque strain (SIVmac) did not develop a helper T-cell response. Furthermore, a vaccine-induced preexisting T-cell reactivity was abrogated after SIVmac infection in vaccine failures. These differences may reflect the different pathogenicity of the two closely related viruses. 相似文献
4.
Sieghart Sopper Susanne Hemm Jürgen Meixensberger Cheik Coulibaly Christiane Stahl-Hennig Gerhard Hunsmann Bernhard Fleckenstein Volker ter Meulen Rüdiger Drries 《Journal of medical primatology》1993,22(2-3):138-146
Paired sera and CSF samples were collected from SIVmac-infected macaques. Animals infected with SIVmac251 maintained low gag and high env-specific antibody levels in plasma. Increasing env-specific antibody titers in CSF were associated in one animal with strong intrathecal synthesis. SIVmac239-infected monkeys revealed high antibody titers of gag and env-specificity, in one animal accompanied by weak intrathecal synthesis of virus-specific antibodies. In all animals, the CD4/CD8 ratio in CSF decreased faster compared to blood. 相似文献
5.
Exorista (=Tachina) larvarum (L.) (Diptera, Tachinidae), a polyphagous parasitoid that attacksLymantria dispar L. andHyphantria cunea (Drury), was rearedin vitro from egg to adult on four tissue culture media-based diets (TMM-FH, SCHNEIDER'S, EX-CELL 400, and SF-900). The kind of tissue
culture media in the diets did not influence the adult yield (34 to 55%) and puparium weight (26–27 mg). Adult yield and the
puparium weight ofE. larvarum developed on TNM-FH and SCHNEIDER'S-based diets containing different amounts ofGalleria mellonella pupal extract (PE) (0, 1.25, 2.5 and 5%), were lower on diets without PE. In diets without PE development times from oviposition
to adult emergence, were shorter on TNM-FH (19 days) than on SCHNEIDER'S-based diet (25–26 days). The adults that developed
on artificial diets were able to parasitize the factitious hostG. mellonella and produce viable progeny. The results demonstrate thatE. larvarum is the most promising parasitoid ever studied forin vitro mass production. 相似文献
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Alphonse Ouédraogo Alfred B. Tiono Désiré Kargougou Jean Baptiste Yaro Esperance Ouédraogo Youssouf Kaboré David Kangoye Edith C. Bougouma Adama Gansane Noelie Henri Amidou Diarra Souleymane Sanon Issiaka Soulama Amadou T. Konate Nora L. Watson Valerie Brown Jenny Hendriks Maria Grazia Pau Isabella Versteege Edison Wiesken Jerald Sadoff Issa Nebie Sodiomon B. Sirima 《PloS one》2013,8(11)
Background
Ad35.CS.01 is a pre-erythrocytic malaria candidate vaccine. It is a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite (CS) surface antigen inserted in a replication deficient Adenovirus 35 backbone. A Phase 1a trial has been conducted in the USA in naïve adults and showed that the vaccine was safe. The aim of this study is to assess the safety and immunogenicity of ascending dosages in sub Saharan Africa.Methods
A double blind, randomized, controlled, dose escalation, phase Ib trial was conducted in a rural area of Balonghin, the Saponé health district (Burkina Faso). Forty-eight healthy adults aged 18-45 years were randomized into 4 cohorts of 12 to receive three vaccine doses (day 0, 28 and 84) of 109, 1010, 5X1010, 1011 vp of Ad35.CS.01 or normal saline by intra muscular injection. Subjects were monitored carefully during the 14 days following each vaccination for non serious adverse events. Severe and serious adverse events were collected throughout the participant study duration (12 months from the first vaccination). Humoral and cellular immune responses were measured on study days 0, 28, 56, 84, 112 and 140.Results
Of the forty-eight subjects enrolled, forty-four (91.7%) received all three scheduled vaccine doses. Local reactions, all of mild severity, occurred in thirteen (27.1%) subjects. Severe (grade 3) laboratory abnormalities occurred in five (10.4%) subjects. One serious adverse event was reported and attributed to infection judged unrelated to vaccine. The vaccine induced both antibody titers and CD8 T cells producing IFNγ and TNFα with specificity to CS while eliciting modest neutralizing antibody responses against Ad35.Conclusion
Study vaccine Ad35.CS.01 at four different dose levels was well-tolerated and modestly immunogenic in this population. These results suggest that Ad35.CS.01 should be further investigated for preliminary efficacy in human challenge models and as part of heterologous prime-boost vaccination strategies.Trial Registration
ClinicalTrials.gov NCT01018459 http://clinicaltrials.gov/ct2/show/NCT01018459 相似文献10.
Silvia M. Ayub-Ferreira Sandrigo Mangini Victor S. Issa Fátima D. Cruz Fernando Bacal Guilherme V. Guimar?es Paulo R. Chizzola Germano E. Concei??o-Souza Fabiana G. Marcondes-Braga Edimar A. Bocchi 《PLoS neglected tropical diseases》2013,7(4)