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21.
Christian Webhofer Philipp Gormanns Stefan Reckow Maria Lebar Giuseppina Maccarrone Tonia Ludwig Benno Pütz John M. Asara Florian Holsboer Inge Sillaber Walter Zieglgänsberger Christoph W. Turck 《Journal of psychiatric research》2013
Most of the commonly used antidepressants block monoamine reuptake transporters to enhance serotonergic or noradrenergic neurotransmission. Effects besides or downstream of monoamine reuptake inhibition are poorly understood and yet presumably important for the drugs' mode of action. In the present study we aimed at identifying hippocampal cellular pathway alterations in DBA/2 mice using paroxetine as a representative Selective Serotonin Reuptake Inhibitor (SSRI). Furthermore we identified biomarker candidates for the assessment of antidepressant treatment effects in plasma. Hippocampal protein levels were compared between chronic paroxetine- and vehicle-treated animals using in vivo15N metabolic labeling combined with mass spectrometry. We also studied the time course of metabolite level changes in hippocampus and plasma using a targeted polar metabolomics profiling platform. In silico pathway analyses revealed profound alterations related to hippocampal energy metabolism. Glycolytic metabolite levels acutely increased while Krebs cycle metabolite levels decreased upon chronic treatment. Changes in energy metabolism were influenced by altered glycogen metabolism rather than by altered glycolytic or Krebs cycle enzyme levels. Increased energy levels were reflected by an increased ATP/ADP ratio and by increased ratios of high-to-low energy purines and pyrimidines. In the course of our analyses we also identified myo-inositol as a biomarker candidate for the assessment of antidepressant treatment effects in the periphery. This study defines the cellular response to paroxetine treatment at the proteome and metabolome levels in the hippocampus of DBA/2 mice and suggests novel SSRI modes of action that warrant consideration in antidepressant development efforts. 相似文献
22.
Michiel Kleinnijenhuis Valerio Zerbi Benno Küsters Cornelis H. Slump Markus Barth Anne-Marie van Cappellen van Walsum 《Cortex; a journal devoted to the study of the nervous system and behavior》2013
One of the most prominent characteristics of the human neocortex is its laminated structure. The first person to observe this was Francesco Gennari in the second half the 18th century: in the middle of the depth of primary visual cortex, myelinated fibres are so abundant that he could observe them with bare eyes as a white line. Because of its saliency, the stria of Gennari has a rich history in cyto- and myeloarchitectural research as well as in magnetic resonance (MR) microscopy. In the present paper we show for the first time the layered structure of the human neocortex with ex vivo diffusion weighted imaging (DWI). To achieve the necessary spatial and angular resolution, primary visual cortex samples were scanned on an 11.7 T small-animal MR system to characterize the diffusion properties of the cortical laminae and the stria of Gennari in particular. The results demonstrated that fractional anisotropy varied over cortical depth, showing reduced anisotropy in the stria of Gennari, the inner band of Baillarger and the deepest layer of the cortex. Orientation density functions showed multiple components in the stria of Gennari and deeper layers of the cortex. Potential applications of layer-specific diffusion imaging include characterization of clinical abnormalities, cortical mapping and (intra)cortical tractography. We conclude that future high-resolution in vivo cortical DWI investigations should take into account the layer-specificity of the diffusion properties. 相似文献
23.
Khawar Ambreen Eppard Elisabeth Roesch Frank Ahmadzadehfar Hojjat Kürpig Stefan Meisenheimer Michael Gaertner Florian. C. Essler Markus Bundschuh Ralph. A. 《Annals of nuclear medicine》2019,33(6):404-413
Annals of Nuclear Medicine - Pre-clinical studies with gallium-68 zoledronate ([68Ga]Ga-DOTAZOL) have proposed it to be a potent bisphosphonate for PET/CT diagnosis of bone diseases and diagnostic... 相似文献
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Depp CA Moore DJ Sitzer D Palmer BW Eyler LT Roesch S Lebowitz BD Jeste DV 《Journal of affective disorders》2007,101(1-3):201-209
BACKGROUND: The frequency, pattern, and correlates of neurocognitive impairment in older patients with bipolar disorder have received little study. We examined neurocognitive abilities in middle-aged and older adults with bipolar disorder to groups with schizophrenia or normal subjects, as well as the relation of neurocognition to clinical characteristics. METHOD: We administered a battery of neurocognitive and clinical measures to older (45-85 years) outpatients with bipolar disorder (n=67), schizophrenia (n=150), and normal comparison subjects (n=85). Within the bipolar group, we assessed the association between neurocognitive performance and psychiatric symptoms, quality of life, and medication status. RESULTS: The group with bipolar disorder differed on nearly all neuropsychological tests compared to normal subjects, with medium effect sizes. Bipolar patients as impaired as those with schizophrenia on half of the tests administered, and performed better on the remaining tests, with small effect sizes. Neurocognitive deficits in bipolar disorder group related to lower quality of life, but not to psychiatric symptom severity or duration of illness. LIMITATIONS: Samples were outpatients with mild-moderate symptoms, and findings may not generalize to acutely ill populations. We lacked data on illness history to examine the cumulative impact of psychopathology. CONCLUSIONS: Among clinically stable middle-aged and older outpatients, bipolar disorder was associated with substantial neurocognitive impairment, with a pattern that was somewhat distinct from that found in schizophrenia. Deficits in the bipolar group were not related to severity or duration of psychiatric symptoms, but were related to quality of life. Bipolar disorder often involve disabling and enduring cognitive impairments in older outpatients. 相似文献
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Eduardo A. Figueiredo Leonor Casilla Loyola Paulo S. Belangero Ândrea Kely Campos Ribeiro-dos-Santos Sidney Emanuel Batista Santos Carina Cohen Andre Wajnsztejn Adrielle Martins de Oliveira Marília C. Smith Alberto de Castro Pochini Carlos V. Andreoli Benno Ejnisman Moises Cohen Mariana F. Leal 《Journal of orthopaedic research》2020,38(1):192-201
Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full-thickness tears of the supraspinatus (Nfemales = 130; Nmales = 81) and 567 age-matched controls (Nfemales = 317; Nmales = 250). Multivariate logistic regressions were carried out with age, gender, genetic ancestry (based on the analysis of 61 biallelic short insertion/deletion polymorphisms), and common co-morbidities (diabetes, dyslipidemia, and smoking habits) as covariates. We observed that carriers of the rare allele of both studied variants of TGFB1, as well as their G/A (rs1800470/rs1800469) haplotype, were less susceptible to RCT (p < 0.05). In contrast, carriers of the G allele of MMP9 rs17576 (p = 0.014) or G/G haplotype (rs17576/rs17577; p < 0.001) had an increased risk for tendon tears. The presence of the T allele of MMP2 rs2285053 (p = 0.033), the T allele of MMP3 rs679620 (p = 0.024), and the TT-genotype of TIMP2 rs2277698 (p = 0.01) was associated with susceptibility to tears, especially in females. In males, the A allele of COL5A1 rs3196378 (p = 0.032) and the G allele of TGFBR1 rs1590 (p = 0.039) were independent risk factors for RCT. The C/T COL5A1 (rs3196378/rs11103544) haplotype was associated with a reduced risk of tears in males (p = 0.03). In conclusion, we identified the genetic variants associated with RCT susceptibility, thereby reinforcing the role of genes involved in the structure and homeostasis of the ECM of tendons in disease development. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:192–201, 2020 相似文献
29.
Ryosuke Matsuura Chieh-Wen Lo Satoshi Wada Junichi Somei Heihachiro Ochiai Takeharu Murakami Norihito Saito Takayo Ogawa Atsushi Shinjo Yoshimi Benno Masaru Nakagawa Masami Takei Yoko Aida 《Viruses》2021,13(5)
SARS-CoV-2 is the causative agent of COVID-19, which is a global pandemic. SARS-CoV-2 is transmitted rapidly via contaminated surfaces and aerosols, emphasizing the importance of environmental disinfection to block the spread of virus. Ultraviolet C radiation and chemical compounds are effective for SARS-CoV-2 disinfection, but can only be applied in the absence of humans due to their toxicities. Therefore, development of disinfectants that can be applied in working spaces without evacuating people is needed. Here we showed that TiO2-mediated photocatalytic reaction inactivates SARS-CoV-2 in a time-dependent manner and decreases its infectivity by 99.9% after 20 min and 120 min of treatment in aerosol and liquid, respectively. The mechanistic effects of TiO2 photocatalyst on SARS-CoV-2 virion included decreased total observed virion count, increased virion size, and reduced particle surface spike structure, as determined by transmission electron microscopy. Damage to viral proteins and genome was further confirmed by western blotting and RT-qPCR, respectively. The multi-antiviral effects of TiO2-mediated photocatalytic reaction implies universal disinfection potential for different infectious agents. Notably, TiO2 has no adverse effects on human health, and therefore, TiO2-induced photocatalytic reaction is suitable for disinfection of SARS-CoV-2 and other emerging infectious disease-causing agents in human habitation. 相似文献
30.
Matthias Christgen MD PhD Oleg Gluz MD Nadia Harbeck MD Ronald E. Kates PhD Mieke Raap MD Henriette Christgen Michael Clemens MD Wolfram Malter MD Benno Nuding MD Bahriye Aktas MD Sherko Kuemmel MD Toralf Reimer MD Andrea Stefek MD Petra Krabisch MD Marianne Just MD Doris Augustin MD Monika Graeser MD Frederick Baehner MD Rachel Wuerstlein MD Ulrike Nitz MD Hans Kreipe MD the West German Study Group PlanB Investigators 《Cancer》2020,126(22):4847-4858