scholarly journals Alpha-1 Acid Glycoprotein as a Biomarker for Subclinical Illness and Altered Drug Binding in Rats

2021 ◽  
Vol 71 (2) ◽  
pp. 123-132
Author(s):  
Catherine A Boyle ◽  
Robert W Coatney ◽  
Alexandra Wickham ◽  
Suman K Mukherjee ◽  
LaVonne D Meunier
Keyword(s):  
Validation Study ◽  
Tissue Injury ◽  
Health Assessment ◽  
Initial Study ◽  
Drug Binding ◽  
Infection Model ◽  
Blood Collection ◽  
Subclinical Infection ◽  
Sprague Dawley ◽  
Acid Glycoprotein

Alpha-1 acid glycoprotein (AGP) is a significant drug binding acute phase protein that is present in rats. AGP levels are known to increase during tissue injury, cancer and infection. Accordingly, when determining effective drug ranges and toxicity limits, consideration of drug binding to AGP is essential. However, AGP levels have not been well established during subclinical infections. The goal of this study was to establish a subclinical infection model in rats using AGP as a biomarker. This information could enhance health surveillance, aid in outlier identification, and provide more informed characterization of drug candidates. An initial study (n = 57) was conducted to evaluate AGP in response to various concentrations of Staphylococcus aureus (S. aureus) in Sprague–Dawley rats with or without implants of catheter material. A model validation study (n = 16) was then conducted using propranolol. Rats received vehicle control or S. aureus and when indicated, received oral propranolol (10 mg/kg). Health assessment and blood collection for measurement of plasma AGP or propranolol were performed over time (days). A dose response study showed that plasma AGP was elevated on day 2 in rats inoculated with S. aureus at 106, 107 or, 108 CFU regardless of implant status. Furthermore, AGP levels remained elevated on day 4 in rats inoculated with 107 or 108 CFUs of S. aureus. In contrast, significant increases in AGP were not detected in rats treated with vehicle or 103 CFU S. aureus. In the validation study, robust elevations in plasma AGP were detected on days 2 and 4 in S. aureus infected rats with or without propranolol. The AUC levels for propranolol on days 2 and 4 were 493 ± 44 h × ng/mL and 334 ± 54 h × ng/mL, respectively), whereas in noninfected rats that received only propranolol, levels were 38 ± 11 h × ng/mL and 76 ± 16. h × ng/mL, respectively. The high correlation between plasma propranolol and AGP demonstrated a direct impact of AGP on drug pharmacokinetics and pharmacodynamics. The results indicate that AGP is a reliable biomarker in this model of subclinical infection and should be considered for accurate data interpretation.

scholarly journals Bed-Based Ballistocardiography: Dataset and Ability to Track Cardiovascular Parameters

Sensors ◽  
2020 ◽  
Vol 21 (1) ◽  
pp. 156
Author(s):  
Charles Carlson ◽  
Vanessa-Rose Turpin ◽  
Ahmad Suliman ◽  
Carl Ade ◽  
Steve Warren ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Stroke Volume ◽  
Systolic Blood Pressure ◽  
Correlation Coefficient ◽  
Pearson Correlation ◽  
Health Assessment ◽  
Initial Study ◽  
Pearson Correlation Coefficient ◽  
Medical Systems ◽  
Cardiovascular Parameters

Background: The goal of this work was to create a sharable dataset of heart-driven signals, including ballistocardiograms (BCGs) and time-aligned electrocardiograms (ECGs), photoplethysmograms (PPGs), and blood pressure waveforms. Methods: A custom, bed-based ballistocardiographic system is described in detail. Affiliated cardiopulmonary signals are acquired using a GE Datex CardioCap 5 patient monitor (which collects ECG and PPG data) and a Finapres Medical Systems Finometer PRO (which provides continuous reconstructed brachial artery pressure waveforms and derived cardiovascular parameters). Results: Data were collected from 40 participants, 4 of whom had been or were currently diagnosed with a heart condition at the time they enrolled in the study. An investigation revealed that features extracted from a BCG could be used to track changes in systolic blood pressure (Pearson correlation coefficient of 0.54 +/− 0.15), dP/dtmax (Pearson correlation coefficient of 0.51 +/− 0.18), and stroke volume (Pearson correlation coefficient of 0.54 +/− 0.17). Conclusion: A collection of synchronized, heart-driven signals, including BCGs, ECGs, PPGs, and blood pressure waveforms, was acquired and made publicly available. An initial study indicated that bed-based ballistocardiography can be used to track beat-to-beat changes in systolic blood pressure and stroke volume. Significance: To the best of the authors’ knowledge, no other database that includes time-aligned ECG, PPG, BCG, and continuous blood pressure data is available to the public. This dataset could be used by other researchers for algorithm testing and development in this fast-growing field of health assessment, without requiring these individuals to invest considerable time and resources into hardware development and data collection.

scholarly journals Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Locomotor Activity ◽  
Tissue Injury ◽  
Male Rats ◽  
Adipose Derived Stem Cells ◽  
Sprague Dawley ◽  
Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

Characterization of Drug Binding with Alpha1-Acid Glycoprotein in Clinical Samples using Ultrafast Affinity Extraction

2021 ◽  
pp. 462240
Author(s):  
Sandya R. Beeram ◽  
Chenhua Zhang ◽  
Kyungah Suh ◽  
William A. Clarke ◽  
David S. Hage
Keyword(s):  
Drug Binding ◽  
Clinical Samples ◽  
Acid Glycoprotein

scholarly journals Increased Migratory and Activation Cell Markers of Peripheral Blood Lymphocytes in an Experimental Model of Nephrotic Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Wagner de Fátima Pereira ◽  
Gustavo Eustáquio Alvim Brito-Melo ◽  
Cláudia Martins Carneiro ◽  
Dirceu de Sousa Melo ◽  
Karine Beatriz Costa ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Peripheral Blood ◽  
Tissue Injury ◽  
Serum Levels ◽  
Peripheral Blood Lymphocytes ◽  
Phenotypic Characterization ◽  
Blood Collection ◽  
Blood Leukocytes ◽  
Male Adult

The present study aimed to evaluate the expression of CD80 and CD18 in subpopulations of peripheral blood leukocytes and oxidative kidney damage in rats with nephrotic syndrome (NS) induced by doxorubicin (Dox) in comparison to control animals at different time points. Male adult Wistar rats were submitted to 24-hour urine and blood collection for biochemical and immunological analysis at 7, 14, 21, and 28 days after Dox injection. After euthanasia, the kidneys were removed for histological analysis and the evaluation of oxidative stress. The phenotypic characterization of leukocytes was performed using flow cytometry. Dox-injected animals exhibited increased CD18 expression in cytotoxic T lymphocytes, NK cells, and monocytes and high CD80 expression in monocytes. Kidney oxidative damage was positively correlated with CD80 expression in monocytes and serum levels of creatinine. These results suggest that phagocytic and cytotoxic cells are preferentially recruited to the tissue injury site, which may contribute to kidney dysfunction in this animal model of NS. The blockade of integrin and costimulatory molecules may provide new therapeutic opportunities for NS.

2021 Frank Stinchfield Award: A novel cemented hip hemiarthroplasty infection model with real-time in vivo imaging in rats

2021 ◽  
Vol 103-B (7 Supple B) ◽  
pp. 9-16
Author(s):  
William J. Hadden ◽  
Mazen Ibrahim ◽  
Mariam Taha ◽  
Kerstin Ure ◽  
Yun Liu ◽  
...  
Keyword(s):  
Real Time ◽  
In Vivo Imaging ◽  
Biofilm Formation ◽  
Joint Infection ◽  
Volumetric Analysis ◽  
In Vivo Model ◽  
Infection Model ◽  
Sprague Dawley ◽  
Hip Hemiarthroplasty

Aims The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. Methods Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. Results All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. Conclusion This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9–16.

scholarly journals Long-term cinnamon consumption improves postoperative recovery of liver resection surgery in aged rats

2020 ◽  
pp. 58-65
Keyword(s):  
Nitric Oxide ◽  
Weight Loss ◽  
Hepatic Resection ◽  
Partial Hepatectomy ◽  
Liver Weight ◽  
Postoperative Recovery ◽  
Normal Diet ◽  
Blood Collection ◽  
Oxide Content ◽  
Sprague Dawley

Introduction: Aging undoubtedly is associated with organ function failure and affects medical/surgical treatments. Free radicals are considered as one of the most common causes of senescence. Liver damage frequently occurs by advance age. Cinnamon (Cinnamomum zeylanicum) is one of the well-known spices in the world tend its antioxidant and hepatoprotective effects have been approved. This study aimed to evaluate the effect of cinnamon consumption on the recovery of partial hepatectomy. Methods and materials: In this experimental study, thirty-two male Sprague-Dawley rats (57 weeks) randomly divided into two equal groups; control (normal diet) and cinnamon (received diet with 1% cinnamon by weight) for 45 weeks. Then, partial hepatectomy (30% of total liver weight) was performed. (Blood collection and weighting were performed prior to hepatectomy and on the 2nd, 10th, and 28th days after the operation. The concentrations of nitric oxide metabolites (NOx), malondialdehyde (MDA), insulin, and glucose were assayed in serum. Results: The results showed that cinnamon consumption prevented postoperative weight loss. The cinnamon was significantly lowered serum MDA concentration 48 hours after hepatectomy as well as it significantly decreased weight loss due to partial hepatectomy on 2nd day after surgery. Change in serum NOx (% of no surgery animals) was dramatically increased following cinnamon consumption on the 2nd and 28th days after surgery. However, cinnamon did not affect serum glucose and insulin concentration. Conclusion: cinnamon improved postoperative outcomes after hepatic resection in rats by attenuation oxidative stress as well as nitric oxide content. It might be considered as a useful dietary recommendation for elderly patients with hepatic resection.

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