preclinical study
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Author(s):  
Bhedita J. Seewoo ◽  
Lauren A. Hennessy ◽  
Liz A. Jaeschke ◽  
Leah A. Mackie ◽  
Sarah J. Etherington ◽  
...  

2021 ◽  
Author(s):  
Rajeev Hatwar ◽  
Sahar Mirpour ◽  
Anilchandra Attaluri ◽  
J. Webster Stayman ◽  
Robert Ivkov ◽  
...  

Abstract Aim In liver CT perfusion, the dual-input maximum slope (DI-MS) method is commonly used to estimate perfusion to aid diagnosis of tumors. The DI-MS method relies on a model that assumes the splenic time-to-peak (TTP) separates arterial and portal venous perfusion, and occurs prior to venous perfusion. In this preclinical study, we examined how the timeliness of splenic TTP affects DI-MS perfusion calculations of liver tumors. Materials and Methods We analyzed imaging data obtained from 11 New Zealand White rabbits bearing a single implanted VX2 tumor in liver. A liver 320-slice CT perfusion protocol (5,400 images per study) was used to generate images. Times for arterial and portal slopes were recorded, and hepatic arterial perfusion (HAP), portal perfusion (HPP) and perfusion index (HPI) for liver and tumor were separately calculated using manual and automated methods. T-test comparisons and Bland-Altman plot analyses were performed. Results Mean tumor TTP occurred at 9.79 s (SD=3.41) and splenic TTP at 9.75 s (SD=4.47, p=0.98). In 3/11 (27.27%) cases, tumor SP occurred prior to spleen (mean difference=1.33 s, SD=1.15 s). In these cases, mean automated HPP values were 43.8% (SD=52.48) higher compared to manually computed ones. There were statistically significant differences between automated and manual methods for normal liver and tumor HPI and HPP (p<0.01 and p<0.0001, respectively), but not HAP values (p=0.125 and p=0.78, respectively). There was also a statistically significant variation between methods for tumor HPP and HPI (p=0.001, respectively). Conclusion In 320-slice CT perfusion of liver in this preclinical model, we observed that tumor TTP occurred prior to splenic TTP in 27.27% of tumors in liver. This temporal relationship affects tumor perfusion calculations and should be identified to address potential deviations of model assumptions.


2021 ◽  
Vol 14 (4) ◽  
pp. 2131-2139
Author(s):  
Faizan Naeem Razali ◽  
Nur Syahirah Izzati Rani ◽  
Muhammad Imran Kamil Mazian ◽  
Ahmad Naeem Mohd Nafi ◽  
Siti Hajar Musa

The polysaccharide isolated from Solanum nigrum was proven to possess an immunomodulatory effect and able to suppress the progression of tumor cells by proxy. However, data on the toxicity profile is still limited. The present preclinical study was conducted to investigate the toxicity potential of the crude polysaccharide sample. The acute toxicity experimental design was adapted from OECD 423 guideline. Nine female BALB/c mice were randomly divided into 3 groups, 3 mice per group (n=3). Mice in group A (first-step treatment) were orally administered with a single treatment of crude polysaccharide sample at concentration 2,000 mg/kg/bw (300 µL). Mice in group B (second-step treatment) were received the single treatment after 24 hours, depending on the observation of mice in group A. Mice in group C served as control. Mortality and clinical signs associated with toxicity were observed within 24 hours of treatment session and for the subsequence 14 days for delay-death detection. Mice body weight was recorded starting at day-0 until day-14 prior to sacrificing at day-15. Blood, liver, and kidney were harvested for toxicology assessment. Within 24 hours of treatment, 1 mouse in group A was found to died, while no mortality and delay-death were observed in groups B and C. Referring to OECD 423, it was estimated that the LD50 of the treated sample was 2,500–5,000 mg/kg/bw. No significant changes (p<0.05) were detected in terms of body weight and organ weight indexes of the treated mice as compared to control. The polysaccharide treatment also revealed no significant elevation in mice serum glucose levels. The present findings indicated that the treatment of crude polysaccharide sample exerted a very mild acute toxicity effect when orally administered at 2,000 mg/kg/bw, with no delay-death.


2021 ◽  
Vol 23 (1) ◽  
pp. 374
Author(s):  
Sabine Stoetzel ◽  
Deeksha Malhan ◽  
Ute Wild ◽  
Christian Helbing ◽  
Fathi Hassan ◽  
...  

Osseointegration is a prerequisite for the long-term success of implants. Titanium implants are preferred for their biocompatibility and mechanical properties. Nonetheless, the need for early and immediate loading requires enhancing these properties by adding bioactive coatings. In this preclinical study, extracellular matrix properties and cellular balance at the implant/bone interface was examined. Polyelectrolyte multilayers of chitosan and gelatin or with chitosan and Hyaluronic acid fabricated on titanium alloy using a layer-by-layer self-assembly process were compared with native titanium alloy. The study aimed to histologically evaluate bone parameters that correlate to the biomechanical anchorage enhancement resulted from bioactive coatings of titanium implants in a rat animal model. Superior collagen fiber arrangements and an increased number of active osteocytes reflected a significant improvement of bone matrix quality at the bone interface of the chitosan/gelatin-coated titan implants over chitosan/hyaluronic acid-coated and native implants. Furthermore, the numbers and localization of osteoblasts and osteoclasts in the reparative and remodeling phases suggested a better cellular balance in the chitosan/Gel-coated group over the other two groups. Investigating the micro-mechanical properties of bone tissue at the interface can elucidate detailed discrepancies between different promising bioactive coatings of titanium alloys to maximize their benefit in future medical applications.


Diagnostics ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 58
Author(s):  
Ali Nahardani ◽  
Simon Leistikow ◽  
Katja Grün ◽  
Martin Krämer ◽  
Karl-Heinz Herrmann ◽  
...  

(1) Background: Pulmonary arterial hypertension (PAH) is a serious condition that is associated with many cardiopulmonary diseases. Invasive right heart catheterization (RHC) is currently the only method for the definitive diagnosis and follow-up of PAH. In this study, we sought a non-invasive hemodynamic biomarker for the diagnosis of PAH. (2) Methods: We applied prospectively respiratory and cardiac gated 4D-flow MRI at a 9.4T preclinical scanner on three different groups of Sprague Dawley rats: baseline (n = 11), moderate PAH (n = 8), and severe PAH (n = 8). The pressure gradients as well as the velocity values were analyzed from 4D-flow data and correlated with lung histology. (3) Results: The pressure gradient between the pulmonary artery and vein on the unilateral side as well as the time-averaged mean velocity values of the small pulmonary arteries were capable of distinguishing not only between baseline and severe PAH, but also between the moderate and severe stages of the disease. (4) Conclusions: The current preclinical study suggests the pulmonary arteriovenous pressure gradient and the time-averaged mean velocity as potential biomarkers to diagnose PAH.


Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1998
Author(s):  
Abdullah F. AlAsmari ◽  
Metab Alharbi ◽  
Faleh Alqahtani ◽  
Fawaz Alasmari ◽  
Mohammed AlSwayyed ◽  
...  

Hepatotoxicity caused by chemotherapeutic drugs (e.g., doxorubicin) is of critical concern in cancer therapy. This study focused on investigating the modulatory effects of diosmin against doxorubicin-induced hepatotoxicity in Male Wistar rats. Male Wistar rats were randomly divided into four groups: Group I was served as control, Group II was treated with doxorubicin (20 mg/kg, intraperitoneal, i.p.), Group III was treated with a combination of doxorubicin and low-dose diosmin (100 mg/kg orally), and Group IV was treated with a combination of doxorubicin and high-dose diosmin (200 mg/kg orally) supplementation. A single dose of doxorubicin (i.p.) caused hepatic impairment, as shown by increases in the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Doxorubicin produced histological abnormalities in the liver. In addition, a single injection of doxorubicin increased lipid peroxidation and reduced glutathione, catalase, and superoxide dismutase (SOD) levels. Importantly, pre-treatment with diosmin restored hepatic antioxidant factors and serum enzymatic activities and reduced the inflammatory and apoptotic-mediated proteins and genes. These findings demonstrate that diosmin has a protective effect against doxorubicin-induced hepatotoxicity.


Author(s):  
Jolien Onsea ◽  
Virginia Post ◽  
Tim Buchholz ◽  
Hella Schwegler ◽  
Stephan Zeiter ◽  
...  

Because of the growing spread of antimicrobial resistance, the use of alternative prevention and treatment strategies is gaining interest. Although the therapeutic potential of bacteriophages has been demonstrated in a number of case reports and series over the past decade, many unanswered questions remain regarding the optimal application protocol.


2021 ◽  
Vol 15 ◽  
Author(s):  
Tomohiro Umeda ◽  
Ayumi Sakai ◽  
Keiko Shigemori ◽  
Ayumi Yokota ◽  
Toru Kumagai ◽  
...  

Amyloidogenic protein oligomers are thought to play an important role in the pathogenesis of neurodegenerative dementia, including Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies. Previously we demonstrated that oral or intranasal rifampicin improved the cognition of APP-, tau-, and α-synuclein-transgenic mice by reducing the amount of Aβ, tau, and α-synuclein oligomers in the brain. In the present study, to explore more effective and safer medications for dementia, we tested the drug combination of rifampicin and resveratrol, which is a multifunctional natural polyphenol with the potential to antagonize the adverse effects of rifampicin. The mixture was intranasally administered to APP-, tau-, and α-synuclein-transgenic mice, and their memory and oligomer-related pathologies were evaluated. Compared with rifampicin and resveratrol alone, the combinatorial medicine significantly improved mouse cognition, reduced amyloid oligomer accumulation, and recovered synaptophysin levels in the hippocampus. The plasma levels of liver enzymes, which reflect hepatic injury and normally increase by rifampicin treatment, remained normal by the combination treatment. Notably, resveratrol alone and the combinatorial medicine, but not rifampicin alone, enhanced the levels of brain-derived neurotrophic factor (BDNF) and its precursor, pro-BDNF, in the hippocampus. Furthermore, the combination showed a synergistic effect in ameliorating mouse cognition. These results show the advantages of this combinatorial medicine with regards to safety and effectiveness over single-drug rifampicin. Our findings may provide a feasible means for the prevention of neurodegenerative dementia that targets toxic oligomers.


Author(s):  
Yin‐Zhe An ◽  
Franz‐Josef Strauss ◽  
Jin‐Young Park ◽  
Yu Qin Shen ◽  
Daniel Stefan Thoma ◽  
...  

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