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71.
Bernhard Antes Philipp Oberkleiner Andreas Nechansky Oliver H.J. Szolar 《Journal of pharmaceutical and biomedical analysis》2010
In this work, we present a comprehensive evaluation of the Agilent Bioanalyzer, a microfluidics-based electrophoretic device that was used for impurity testing of a monoclonal antibody (mAb). We compared the system to SDS-PAGE, both operated under non-reducing conditions and found a significant improvement of accuracy for the Bioanalyzer. In addition, the latter exhibited a larger assay range and lower limit of quantitation (LOQ) based on a predefined total error limit of ±30%. However, during method qualification applying a three-factor nested design with two operators performing duplicate measurements per day, each on 4 different days, we observed unpredictable recurring quantitative outliers using the chip-based system. In-depth analysis on multiple runs with various chip lots confirmed the above finding and indicated that most likely on-chip dye labeling and/or post-column background fluorescence elimination are not compatible with the large size of the intact antibody as similar findings were observed for myosin used as upper marker for time correction. Interestingly, after reducing the intact antibody into light and heavy chain, we resolved the outlier issue. Eventually, requalification of the micro-fabricated analytical device under reducing conditions revealed only 1 out of 32 quality control samples (QCs) exceeding the ±30% total error limits. 相似文献
72.
Kylie Kavanagh Soraya Sajadian Kurt A. Jenkins Martha D. Wilson J. Jeffery Carr Janice D. Wagner Lawrence L. Rudel 《Nutrition Research》2010
Industrially produced trans-fatty acids (TFAs) consumed in Western diets are incorporated into maternal and fetal tissues and are passed linearly to offspring via breast milk. We hypothesized that TFA exposure in utero and during lactation in infants would promote obesity and poor glycemic control as compared with unmodified fatty acids. We further hypothesized that in utero exposure alone may program for these outcomes in adulthood. To test this hypothesis, we fed female C57/BL6 mice identical Western diets that differed only in cis- or trans-isomers of C18:1 and then aimed to determine whether maternal transfer of TFAs through pregnancy and lactation alters growth, body composition, and glucose metabolism. Mice were unexposed, exposed during pregnancy, during lactation, or throughout pregnancy and lactation to TFA. Body weight and composition (by computed tomography) and glucose metabolism were assessed at weaning and adulthood. Trans-fatty acid exposure through breast milk caused significant early growth retardation (P < .001) and higher fasting glucose (P = .01), but insulin sensitivity was not different. Elevated plasma insulin-like growth factor-1 in mice consuming TFA-enriched milk (P = .02) may contribute to later catch-up growth and leanness and preserved peripheral insulin sensitivity observed in these mice. Mice exposed to TFA in utero underwent rapid early neonatal growth with TFA-free breast milk and had significantly impaired insulin sensitivity (P < .05) and greater abdominal fat (P = .01). We conclude that very early catch-up growth resulted in impaired peripheral insulin sensitivity in this model of diet-related fetal and neonatal programming. Trans-fatty acid surprisingly retarded growth and adiposity while still adversely affecting glucose metabolism. 相似文献
73.
Junzo Kamei Shigeo Miyata Masahiro Ohsawa 《Progress in neuro-psychopharmacology & biological psychiatry》2009
The traditional Japanese Kampo medicine Yokukansan (YKS, Yi-gan san in Chinese) has been demonstrated to improve the behavioral and psychological symptoms of dementia (BPSD), such as anxiety, hallucinations, agitation and irritability. The aim of this study was to elucidate the mechanism of the anxiolytic-like effects of YKS and Chotoko, which is an active component of YKS. Oral treatment with YKS (300 and 1000 mg/kg) significantly increased the number of head-dipping behaviors in mice in the hole-board test. Head-dipping behavior in mice was also significantly increased by treatment with Chotoko (50 and 100 mg/kg, p.o.). In addition, oral treatment with the water-extracted fractions from YKS (YKS-W; 250 and 500 mg/kg, p.o.) and Chotoko (Chotoko-W; 10 and 30 mg/kg) significantly increased the number of head-dipping behaviors in mice. On the other hand, treatment with the methanol-extracted fraction of YKS (YKS-Met; 15 and 30 mg/kg, p.o.) did not affect head-dipping behavior. The total distance and number of rearing behaviors were not affected by treatment with any of these drugs. The increase in the number of head-dipping behaviors by treatment with YKS-W (500 mg/kg, p.o.) and Chotoko-W (30 mg/kg, p.o.) was inhibited by pretreatment with the benzodiazepine receptor antagonist flumazenil (1 mg/kg, i.v.). In the elevated plus-maze test, the percentage of time spent in open arms was increased in YKS (1000 mg, p.o.) treatment. Based on these results, we suggest that YKS produces an anxiolytic-like effect mediated by the benzodiazepine system. Chotoko is an effective component of YKS for producing an anxiolytic-like effect. The effective compound(s) should be contained, at least in part, in the water-soluble fraction of YKS. 相似文献
74.
There is a need for appropriate methods for the analysis of very small samples of continuous repeated measurements. A key feature of such analyses is the role played by the covariance matrix of the repeated observations. When subjects are few it can be difficult to assess the fit of parsimonious structures for this matrix, while the use of an unstructured form may lead to a serious lack of power. The Kenward–Roger adjustment is now widely adopted as a means of providing an appropriate inferences in small samples, but does not perform adequately in very small samples. Adjusted tests based on the empirical sandwich estimator can be constructed that have good nominal properties, but are seriously underpowered. Further, when such data are incomplete, or unbalanced, or non‐saturated mean models are used, exact distributional results do not exist that justify analyses with any sample size. In this paper, a modification of Box's correction applied to a linear model‐based F‐statistic is developed for such small sample settings and is shown to have both the required nominal properties and acceptable power across a range of settings for repeated measurements. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
75.
Sayamwong E. Hammack Ji-Dong Guo Rimi Hazra Joanna Dabrowska Karyn M. Myers Donald G. Rainnie 《Progress in neuro-psychopharmacology & biological psychiatry》2009
Substantial evidence has suggested that the activity of the bed nucleus of the stria terminalis (BNST) mediates many forms of anxiety-like behavior in human and non-human animals. These data have led many investigators to suggest that abnormal processing within this nucleus may underlie anxiety disorders in humans, and effective anxiety treatments may restore normal BNST functioning. Currently some of the most effective treatments for anxiety disorders are drugs that modulate serotonin (5-HT) systems, and several decades of research have suggested that the activation of 5-HT can modulate anxiety-like behavior. Despite these facts, relatively few studies have examined how activity within the BNST is modulated by 5-HT. Here we review our own investigations using in vitro whole-cell patch-clamp electrophysiological methods on brain sections containing the BNST to determine the response of BNST neurons to exogenous 5-HT application. Our data suggest that the response of BNST neurons to 5-HT is complex, displaying both inhibitory and excitatory components, which are mediated by 5-HT1A, 5-HT2A, 5-HT2C and 5-HT7 receptors. Moreover, we have shown that the selective activation of the inhibitory response to 5-HT reduces anxiety-like behavior, and we describe data suggesting that the activation of the excitatory response to 5-HT may be anxiogenic. We propose that in the normal state, the function of 5-HT is to dampen activity within the BNST (and consequent anxiety-like behavior) during exposure to threatening stimuli; however, we suggest that changes in the balance of the function of BNST 5-HT receptor subtypes could alter the response of BNST neurons to favor excitation and produce a pathological state of increased anxiety. 相似文献
76.
Hou G Dick R Abrams GD Brewer GJ 《The Journal of laboratory and clinical medicine》2005,146(5):299-303
Cardiac toxicity is the limiting factor in therapy with doxorubicin, an otherwise useful cancer drug. In this article we detail our study of a mouse model of doxorubicin-induced cardiac toxicity in which, after 4 days' treatment, doxorubicin caused marked increases in plasma concentrations of creatine kinase, lactic dehydrogenase, and troponin I, indicators of cardiac injury; marked increases in the plasma concentrations of tumor necrosis factor-alpha and interleukin-1(beta), both inflammatory cytokines; and a marked increase in the plasma concentration of interleukin-2, an indicator of cytotoxic T-cell activation. Therapy with tetrathiomolybdate, designed to limit copper availability, eliminated almost all of the increases of these six parameters in plasma. The marked protection against cardiac injury by doxorubicin in tetrathiomolybdate-treated animals suggests that tetrathiomolybdate would be of use clinically in helping prevent doxorubicin toxicity in patients. In other preclinical work, it has been shown that tetrathiomolybdate potentiates the chemotherapeutic effect of doxorubicin in cancer, so a double benefit might accrue clinically from the combined use of tetrathiomolybdate and doxorubicin. The mechanism by which tetrathiomolybdate protects against doxorubicin toxicity is of considerable interest. Our working hypothesis, based on the inhibition of interleukin-2 by tetrathiomolybdate as shown here, is that tetrathiomolybdate interrupts the inflammatory cascade at the activated-T-lymphocyte stage. 相似文献
77.
Fabbi P Ghigliotti G Brunelli C Balbi M Spallarossa P Rossettin P Barsotti A Odetti P Garibaldi S 《The Journal of laboratory and clinical medicine》2004,143(2):99-105
Increased oxidative stress is associated with rapid progression of atherosclerosis. In this study we sought to determine whether premature onset of clinical coronary atherosclerosis is associated with increased levels of lipid peroxidation. We measured plasma levels of malondialdehyde (MDA), using high-pressure liquid chromatography, in 42 male patients with early- (<56 years) or late-onset (>64 years) unstable angina and in 2 age-matched control groups (n=20). Plasma MDA levels were higher in the patients with unstable angina than in the control groups (1.57 +/- 0.07 vs 1.14 +/- 0.03 nmol/mL; P<.001). Patients with early-onset angina showed higher MDA levels than those in late-onset patients (1.75 +/- 0.11 vs 1.44 +/- 0.097 nmol/mL; P<.05), despite a similar prevalence of risk factors for atherothrombosis. The inflammatory component, measured with the use of a high-sensitivity enzyme-linked immunosorbent assay for C-reactive protein, and platelet activity, measured as prothrombin fragment 1+2, failed to predict MDA level. Fasting glucose (P<.05) was the best predictor of MDA level in patients with early-onset unstable angina; uric acid (P=.09) and body-mass index (P=.15) showed trends toward significant correlation with MDA level in the same group of patients. Metabolic abnormalities related to insulin resistance in patients with premature coronary atherosclerosis appear to be important mediators of major plasma oxidative damage. 相似文献
78.
79.
Magnus D. Potgieter Parastu Meidany 《Burns : journal of the International Society for Burn Injuries》2018,44(3):596-602
Background
The nanocrystalline silver (NCS) dressing Acticoat is commonly used in clinical practice for the treatment of burns and other open wounds as a topical antimicrobial. The dressing may dry resulting in traumatic dressing changes; hence the variety of contact layer dressings used in conjunction with it. Dressing combinations that do not permit NCS penetration are not cost effective and deprives the wound of the needed anti-microbial.Methods
Common wound pathogens were subjected to a variety of contact layer dressings underlying the NCS dressings. The zone of inhibition (ZOI) obtained was measured and compared to a control.Results
Intrasite gel demonstrated a synergistic effect with Acticoat. Iruxol exhibits antagonism by preventing penetration and is known to be partially deactivated by NCS. Intrasite conformable and Adaptic allowed partial penetration while the discs of Biobrane, unstretched/non-fenestrated Pelnac and Telfa transparent film did not allow for sufficient penetration to inhibit the underlying bacteria in this study. The cadaver skin from the South African skin bank (Tshwane university of Technology) displayed a greater antimicrobial effect than even the Acticoat control.Conclusion
Our results illustrate that we should perhaps reconsider dressing combination choices with Acticoat in view of their redundancy or synergistic effect. 相似文献80.
Gina L. Griffith Barbara Wirostko Hee-Kyoung Lee Lauren E. Cornell Jennifer S. McDaniel David O. Zamora Anthony J. Johnson 《Burns : journal of the International Society for Burn Injuries》2018,44(5):1179-1186