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Jerry R. Nedelman Ekaterina Gibiansky Francis L. S. Tse Christine Babiuk 《Journal of pharmacokinetics and pharmacodynamics》1993,21(3):323-334
Five major objectives for pharmacokinetic investigations in support of toxicity studies are identified as follows: Assess whether animals exhibited measurable blood concentrations in a dose-dependent manner; estimate average area under the concentration- time curve (AUC)and maximal concentration (C
max
)for each treatment group; elucidate general patterns in the concentration-time (CxT)profile, and summarize relationships between CxTand treatment group; determine CxTdependence on day into study; and judge interanimal variability and identify any animals with unusual concentration response. Such objectives are generally addressed in rodent toxicity studies by including satellite animals in the study. Satellite animals are extra animals dosed as per protocol but not subjected to toxicological and pathological observations and tests. Instead, they are used exclusively for the evaluation of pharmacokinetic characteristics of the test compound. In this paper, methods are described for achieving the five listed pharmacokinetic objectives in rodent toxicity studies without the use of satellite animals. A rat toxicity study is presented as an example. 相似文献
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Aleksey Bychkov Vyacheslav Koptev Varvara Zaharova Polina Reshetnikova Elena Trofimova Elena Bychkova Ekaterina Podgorbunskikh Oleg Lomovsky 《Nutrients》2022,14(10)
This study presents findings on the biological action of an integrated supplement containing the following components involved in osteogenesis and mineralization: vitamin D and silicon in the bioavailable and soluble form. A hypothesis that these components potentiate one another’s action and make calcium absorption by the body more efficient was tested. Biological tests of the effect of vitamin D and silicon chelates on bone fracture healing and bone turnover were conducted using ICR mice and albino Wistar rats. Radiographic and biochemical studies show that the supplement simultaneously containing silicon chelates and vitamin D stimulates bone tissue regeneration upon mechanical defects and accelerates differentiation of osteogenic cells, regeneration of spongy and compact bones, and restoration of bone structure due to activation of osteoblast performance. Bone structure restoration was accompanied by less damage to skeletal bones, apparently due to better absorption of calcium from food. The studied supplement has a similar effect when used to manage physiologically induced decalcification, thus holding potential for the treatment of osteomalacia during pregnancy or occupational diseases (e.g., for managing bone decalcification in astronauts). 相似文献
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Abnormalities of the executive control network in multiple sclerosis phenotypes: An fMRI effective connectivity study 下载免费PDF全文
Ekaterina Dobryakova Maria Assunta Rocca Paola Valsasina Angelo Ghezzi Bruno Colombo Vittorio Martinelli Giancarlo Comi John DeLuca Massimo Filippi 《Human brain mapping》2016,37(6):2293-2304
The Stroop interference task is a cognitively demanding task of executive control, a cognitive ability that is often impaired in patients with multiple sclerosis (MS). The aim of this study was to compare effective connectivity patterns within a network of brain regions involved in the Stroop task performance between MS patients with three disease clinical phenotypes [relapsing‐remitting (RRMS), benign (BMS), and secondary progressive (SPMS)] and healthy subjects. Effective connectivity analysis was performed on Stroop task data using a novel method based on causal Bayes networks. Compared with controls, MS phenotypes were slower at performing the task and had reduced performance accuracy during incongruent trials that required increased cognitive control. MS phenotypes also exhibited connectivity abnormalities reflected as weaker shared connections, presence of extra connections (i.e., connections absent in the HC connectivity pattern), connection reversal, and loss. In SPMS and the BMS groups but not in the RRMS group, extra connections were associated with deficits in the Stroop task performance. In the BMS group, the response time associated with correct responses during the congruent condition showed a positive correlation with the left posterior parietal → dorsal anterior cingulate connection. In the SPMS group, performance accuracy during the congruent condition showed a negative correlation with the right insula → left insula connection. No associations between extra connections and behavioral performance measures were observed in the RRMS group. These results suggest that, depending on the phenotype, patients with MS use different strategies when cognitive control demands are high and rely on different network connections. Hum Brain Mapp, 37:2293–2304, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
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Takafumi Yanagisawa Tatsushi Kawada Hadi Mostafaei Reza Sari Motlagh Fahad Quhal Ekaterina Laukhtina Pawel Rajwa Markus von Deimling Alberto Bianchi Maximilian Pallauf Benjamin Pradere Pierre I. Karakiewicz Jun Miki Takahiro Kimura Shahrokh F. Shariat 《BJU international》2023,132(2):132-145