scholarly journals In vivo evaluation of bending strengths and degradation rates of different magnesium pin designs for oral stapler

2020 ◽  
Vol 18 ◽  
pp. 228080001983640
Author(s):  
Wenjun Li ◽  
Fusong Yuan ◽  
Jing Bai ◽  
Junyao Cheng ◽  
Hongxiang Li ◽  
...  
Keyword(s):  
Magnesium Alloys ◽  
Degradation Rate ◽  
Bending Strength ◽  
Sprague Dawley ◽  
In Vivo Evaluation ◽  
Cross Sectional ◽  
Round Cross Section ◽  
Sd Rats ◽  
Degradation Rates

Magnesium alloys have been potential biodegradable implants in the areas of bone, cardiovascular system, gastrointestinal tract, and so on. The purpose of this study is to evaluate Mg–2Zn alloy degradation as a potential suture material. The study included Sprague–Dawley (SD) rats in vivo. In 24 male SD rats, tests in the leg muscle were conducted using traditional surgical incision and insertion of magnesium alloys of different designs into the tissue. The material degradation topography, elemental composition, and strength of the pins were analyzed. This paper explores magnesium pins with different cross-sectional shapes and diameters to establish a suitable pin diameter and shape for use as an oral stapler, which must have a good balance of degradation rate and strength. The results showed there were good bending strengths over different degradation periods in groups with diameters of 0.8 mm and 0.5 mm, and no significantly different bending strength between the groups of triangle and round cross-section shapes with same diameter of 0.3 mm, although the degradation rate still needs to be improved.

Toxicokinetic and Genotoxicity Study of NNK in Male Sprague-Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

2021 ◽  
Author(s):  
Shu-Chieh Hu ◽  
Matthew S Bryant ◽  
Estatira Sepehr ◽  
Hyun-Ki Kang ◽  
Raul Trbojevich ◽  
...  
Keyword(s):  
Human Lung ◽  
Inhalation Exposure ◽  
Systemic Exposure ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sd Rats ◽  
New Information ◽  
Sprague Dawley Rats ◽  
Tissue Specimens

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.

Zucker Lean Rats With Hepatic Steatosis Recapitulate Asymptomatic Metabolic Syndrome and Exhibit Greater Sensitivity to Drug-Induced Liver Injury Compared With Standard Nonclinical Sprague-Dawley Rat Model

2020 ◽  
Vol 48 (8) ◽  
pp. 994-1007
Author(s):  
Timothy P. LaBranche ◽  
Anna K. Kopec ◽  
Srinivasa R. Mantena ◽  
Brett D. Hollingshead ◽  
Andrew W. Harrington ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Pharmaceutical Industry ◽  
Liver Injury ◽  
Hepatic Steatosis ◽  
Sprague Dawley ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Sd Rats ◽  
Normal Chow

Fatty liver disease is a potential risk factor for drug-induced liver injury (DILI). Despite advances in nonclinical in vitro and in vivo models to assess liver injury during drug development, the pharmaceutical industry is still plagued by idiosyncratic DILI. Here, we tested the hypothesis that certain features of asymptomatic metabolic syndrome (namely hepatic steatosis) increase the risk for DILI in certain phenotypes of the human population. Comparison of the Zucker Lean (ZL) and Zucker Fatty rats fed a high fat diet (HFD) revealed that HFD-fed ZL rats developed mild hepatic steatosis with compensatory hyperinsulinemia without increases in liver enzymes. We then challenged steatotic HFD-fed ZL rats and Sprague-Dawley (SD) rats fed normal chow, a nonclinical model widely used in the pharmaceutical industry, with acetaminophen overdose to induce liver injury. Observations in HFD-fed ZL rats included increased liver injury enzymes and greater incidence and severity of hepatic necrosis compared with similarly treated SD rats. The HFD-fed ZL rats also had disproportionately higher hepatic drug accumulation, which was linked with abnormal hepatocellular efflux transporter distribution. Here, we identify ZL rats with HFD-induced hepatic steatosis as a more sensitive nonclinical in vivo test system for modeling DILI compared with SD rats fed normal chow.

scholarly journals Enhanced Oral Bioavailability of Celecoxib Nanocrystalline Solid Dispersion based on Wet Media Milling Technique: Formulation, Optimization and In Vitro/In Vivo Evaluation

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 328 ◽  
Author(s):  
Zhuang Ding ◽  
Lili Wang ◽  
Yangyang Xing ◽  
Yanna Zhao ◽  
Zhengping Wang ◽  
...  
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Stability Study ◽  
Sprague Dawley ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Celecoxib (CLX), a selective COX-2 inhibitor, is a biopharmaceutics classification system (BCS) class II drug with its bioavailability being limited by thepoor aqueoussolubility. The purpose of this study was to develop and optimize CLX nanocrystalline(CLX-NC) solid dispersion prepared by the wet medium millingtechnique combined with lyophilizationto enhance oral bioavailability. In formulation screening, the resulting CLX-NC usingpolyvinylpyrrolidone (PVP) VA64 and sodiumdodecyl sulfate (SDS) as combined stabilizers showed the minimum particle size and a satisfactory stability. The formulation and preparation processwere further optimized by central composite experimentaldesign with PVP VA64 concentration (X1), SDS concentration (X2) and milling times (X3) as independent factors and particle size (Y1), polydispersity index (PDI, Y2) and zeta potential (Y3) as response variables. The optimal condition was determined as a combination of 0.75% PVP VA64, 0.11% SDS with milling for 90 min.The particle size, PDI and zeta potential of optimized CLX-NC were found to be 152.4 ± 1.4 nm, 0.191 ± 0.012 and −34.4 ± 0.6 mV, respectively. The optimized formulation showed homogeneous rod-like morphology as observed by scanning electron microscopy and was in a crystalline state as determined by differential scanning calorimetry and powder X-ray diffraction. In a storage stability study, optimized CLX-NC exhibited an excellent physical stability during six months’ storage at both the refrigeration and room conditions. In vivo pharmacokinetic research in Sprague-Dawley ratsdisplayed that Cmax and AUC0–∞ of CLX-NC were increased by 2.9 and 3.1 fold, compared with physical mixture. In this study, the screening and optimizing strategy of CLX-NC formulation represents a commercially viable approach forenhancing the oral bioavailability of CLX.

scholarly journals Efficacy of 670 nm Light Therapy to Protect against Photoreceptor Cell Death Is Dependent on the Severity of Damage

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Joshua A. Chu-Tan ◽  
Matt Rutar ◽  
Kartik Saxena ◽  
Yunlu Wu ◽  
Lauren Howitt ◽  
...  
Keyword(s):  
Cell Death ◽  
Photoreceptor Cell ◽  
Light Therapy ◽  
Sprague Dawley ◽  
Respiratory Capacity ◽  
Extracellular Flux ◽  
Sd Rats ◽  
Lower Light

Photobiomodulation at a wavelength of 670 nm has been shown to be effective in preventing photoreceptor cell death in the retina. We treated Sprague-Dawley (SD) rats with varying doses of 670 nm light (9; 18; 36; 90 J/cm2) before exposing them to different intensities of damaging white light (750; 1000; 1500 lux). 670 nm light exhibited a biphasic response in its amelioration of cell death in light-induced degenerationin vivo. Lower light damage intensities required lower doses of 670 nm light to reduce TUNEL cell death. At higher damage intensities, the highest dose of 670 nm light showed protection.In vitro, the Seahorse XFe96 Extracellular Flux Analyzer revealed that 670 nm light directly influences mitochondrial metabolism by increasing the spare respiratory capacity of mitochondria in 661 W photoreceptor-like cells in light damaged conditions. Our findings further support the use of 670 nm light as an effective treatment against retinal degeneration as well as shedding light on the mechanism of protection through the increase of the mitochondrial spare respiratory capacity.

scholarly journals In Vivo Simulation of Magnesium Degradability Using a New Fluid Dynamic Bench Testing Approach

2019 ◽  
Vol 20 (19) ◽  
pp. 4859 ◽  
Author(s):  
Ole Jung ◽  
Dario Porchetta ◽  
Marie-Luise Schroeder ◽  
Martin Klein ◽  
Nils Wegner ◽  
...  
Keyword(s):  
Degradation Rate ◽  
Test Bench ◽  
Fluid Dynamic ◽  
Dynamic Test ◽  
Gas Production ◽  
Hydrogen Gas ◽  
Human Blood Plasma ◽  
Degradation Rates

The degradation rate of magnesium (Mg) alloys is a key parameter to develop Mg-based biomaterials and ensure in vivo-mechanical stability as well as to minimize hydrogen gas production, which otherwise can lead to adverse effects in clinical applications. However, in vitro and in vivo results of the same material often differ largely. In the present study, a dynamic test bench with several single bioreactor cells was constructed to measure the volume of hydrogen gas which evolves during magnesium degradation to indicate the degradation rate in vivo. Degradation medium comparable with human blood plasma was used to simulate body fluids. The media was pumped through the different bioreactor cells under a constant flow rate and 37 °C to simulate physiological conditions. A total of three different Mg groups were successively tested: Mg WE43, and two different WE43 plasma electrolytically oxidized (PEO) variants. The results were compared with other methods to detect magnesium degradation (pH, potentiodynamic polarization (PDP), cytocompatibility, SEM (scanning electron microscopy)). The non-ceramized specimens showed the highest degradation rates and vast standard deviations. In contrast, the two PEO samples demonstrated reduced degradation rates with diminished standard deviation. The pH values showed above-average constant levels between 7.4–7.7, likely due to the constant exchange of the fluids. SEM revealed severe cracks on the surface of WE43 after degradation, whereas the ceramized surfaces showed significantly decreased signs of corrosion. PDP results confirmed the improved corrosion resistance of both PEO samples. While WE43 showed slight toxicity in vitro, satisfactory cytocompatibility was achieved for the PEO test samples. In summary, the dynamic test bench constructed in this study enables reliable and simple measurement of Mg degradation to simulate the in vivo environment. Furthermore, PEO treatment of magnesium is a promising method to adjust magnesium degradation.

scholarly journals Mg-Zn-Ca Alloys for Hemostasis Clips for Vessel Ligation: In Vitro and In Vivo Studies of Their Degradation and Response

Materials ◽  
2020 ◽  
Vol 13 (13) ◽  
pp. 3039 ◽  
Author(s):  
Yen-Hao Chang ◽  
Chun Chieh Tseng ◽  
Chih-Yeh Chao ◽  
Chung-Hwan Chen ◽  
Sung-Yen Lin ◽  
...  
Keyword(s):  
Degradation Rate ◽  
Protective Layer ◽  
Dip Coating ◽  
In Vivo Studies ◽  
Surface Measurement ◽  
In Vivo Experiments ◽  
Degradation Rates ◽  
And Behavior

To control the degradation rate of magnesium (Mg) alloys, chitosan (CHI) and L-glutamic acid (LGA) were used as coatings on Mg-Zn-Ca alloys via dip coating. In this study, either two or seven CHI/LGA layers were applied as a coating on Mg-2.8Zn-0.8Ca alloy (ZX31) and Mg-2.8Zn-0.8Ca hemostasis clips (ZX31 clips). The morphologies, compositions, and surface roughness of the specimens were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, and surface measurement devices. The degradation rates and behavior of the specimens were evaluated by immersing them in simulated body fluids and by applying these ZX31 clips on rabbits’ uterine tubes for five weeks. The specimen with seven layers (ZX31(CHI/LGA)7) exhibited improved corrosion behavior when compared with ZX31 or ZX31(CHI/LGA)2, with a reduced degradation rate of the Mg alloy in a simulated body environment. In vivo experiments showed that ZX31 clips exhibited good biocompatibilities in each group but could not maintain the clamping function for five weeks. The weight loss of ZX31(CHI/LGA)7 was significantly lower than that of the other groups. Consequently, it was verified that CHI can be used as a protective layer on a magnesium alloy surface via in vitro and in vivo experiments.

scholarly journals Osseointegration of Alkali-Modified NANOZR Implants: An In Vivo Study

2019 ◽  
Vol 20 (4) ◽  
pp. 842 ◽  
Author(s):  
Satoshi Komasa ◽  
Mariko Nishizaki ◽  
Honghao Zhang ◽  
Seiji Takao ◽  
Derong Yin ◽  
...  
Keyword(s):  
Bending Strength ◽  
Bone Marrow Cells ◽  
Alkali Treatment ◽  
Treated Group ◽  
Fluorescent Labeling ◽  
Male Rats ◽  
Sprague Dawley ◽  
Bone Differentiation

Ingredients and surface modification methods are being continually developed to improve osseointegration of dental implants and reduce healing times. In this study, we demonstrate in vitro that, by applying concentrated alkali treatment to NANOZR with strong bending strength and fracture toughness, a significant improvement in the bone differentiation of rat bone marrow cells can be achieved. We investigated the influence of materials modified with this treatment in vivo, on implanted surrounding tissues using polychrome sequential fluorescent labeling and micro-computer tomography scanning. NANOZR implant screws in the alkali-treated group and the untreated group were evaluated after implantation in the femur of Sprague–Dawley male rats, indicating that the amount of new bone in the alkali-modified NANOZR was higher than that of unmodified NANOZR. Alkali-modified NANOZR implants proved to be useful for the creation of new implant materials.

scholarly journals P0884MYO-INOSITOL HEXAPHOSPHATE PEGYLATION IMPROVES BIOAVAILABILITY BUT REDUCES ITS ANTI-VASCULAR CALCIFICATION EFFECT IN RATS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
M Mar Pérez ◽  
Miguel David Ferrer Reynes ◽  
Joaquín Ortega-Castro ◽  
Firas Bassissi ◽  
Joan Perelló ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Density Functional ◽  
Inositol Phosphates ◽  
Crystal Surface ◽  
Density Functional Theory Calculations ◽  
Sprague Dawley ◽  
Inositol Hexaphosphate ◽  
Sd Rats

Abstract Background and Aims Vascular calcification (VC) is a major contributor to increased morbidity and mortality in End Stage Kidney Disease (ESKD) patients undergoing dialysis. SNF472, a salt of inositol hexaphosphate (InsP6), is a selective calcification inhibitor that interferes in the formation and growth of ectopic hydroxyapatite (HAP). SNF472 is currently in Phase 3 clinical trials for the treatment of calciphylaxis in ESKD patients on dialysis. Inositol-1,2,3,5-tetraphosphate-4,6-bisPEG100 (InsP4bisPEG or INS3001) results from the PEGylation of inositol tetraphosphate (InsP4) with polyethylene glycol (PEG) 100. Our aim was to compare the relative bioavailability of SNF472 and InsP4bisPEG and their efficacy in the inhibition of calcification in silico, in vitro and in vivo. Method Subcutaneous (10 mg/kg) pharmacokinetics of InsP4bisPEG and SNF472 were assessed in Sprague Dawley (SD) rats. To evaluate the adsorption binding affinity (Eads) of SNF472, InsP4bisPEG and other inositol phosphates to the HAP crystal surface, computational studies were performed using Density Functional Theory calculations with DMOL3 (MS2016). The in vitro efficacy of the compounds was evaluated using a pharmacodynamic assay to measure the calcification potential of human plasma. An in vivo efficacy study (calcification induced by 3 consecutives daily s.c. administrations of 150 kIU/kg vitamin D3) was performed with SD rats receiving s.c. vehicle, or equimolar doses (36 µmol/kg) of SNF472 or InsP4bisPEG once daily. Results The PEGylation of inositol tetraphosphate in positions 4 and 6 increased the exposure and t1/2 of the compound when given subcutaneously compared to SNF472. Molecular modelling revealed that SNF472 binds to the HAP surface with higher affinity than InsP4bisPEG and INSP4 (ΔEads=-352 kcal/mol for SNF472, ΔEads=-177 kcal/mol for InsP4bisPEG and ΔEads=-146 Kcal/mol for InsP4, taking inositol as reference). These results were correlated with the inhibition of calcium phosphate crystallization in plasma in vitro. SNF472 treated animals presented significantly lower calcium levels in aorta, which were 38% and 55% lower than placebo and InsP4bisPEG treated animals, respectively. Conclusion The differential pharmacokinetic profile of InsP4bisPEG (INS3001) does not translate into higher, but lower, efficacy than SNF472 against vascular calcification when comparing equimolar doses.

scholarly journals The Effect of Sertoli Cells on Xenotransplantation and Allotransplantation of Ventral Mesencephalic Tissue in a Rat Model of Parkinson’s Disease

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1420
Author(s):  
Yun-Ting Jhao ◽  
Chuang-Hsin Chiu ◽  
Chien-Fu F. Chen ◽  
Ta-Kai Chou ◽  
Yi-Wen Lin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Sertoli Cells ◽  
Dopaminergic Neurons ◽  
Sprague Dawley ◽  
Drug Induced ◽  
In Vivo Evaluation ◽  
Ventral Mesencephalic

Intra-striatal transplantation of fetal ventral mesencephalic (VM) tissue has a therapeutic effect on patients with Parkinson’s disease (PD). Sertoli cells (SCs) possess immune-modulatory properties that benefit transplantation. We hypothesized that co-graft of SCs with VM tissue can attenuate rejection. Hemi-parkinsonian rats were generated by injecting 6-hydroxydopamine into the right medial forebrain bundle of Sprague Dawley (SD) rats. The rats were then intrastriatally transplanted with VM tissue from rats or pigs (rVM or pVM), with/without a co-graft of SCs (rVM+SCs or pVM+SCs). Recovery of dopaminergic function and survival of the grafts were evaluated using the apomorphine-induced rotation test and small animal-positron emission tomography (PET) coupled with [18F] DOPA or [18F] FE-PE2I, respectively. Immunohistochemistry (IHC) examination was used to determine the survival of the grafted dopaminergic neurons in the striatum and to investigate immune-modulatory effects of SCs. The results showed that the rVM+SCs and pVM+SCs groups had significantly improved drug-induced rotational behavior compared with the VM alone groups. PET revealed a significant increase in specific uptake ratios (SURs) of [18F] DOPA and [18F] FE-PE2I in the grafted striatum of the rVM+SCs and pVM+SCs groups as compared to that of the rVM and pVM groups. SC and VM tissue co-graft led to better dopaminergic (DA) cell survival. The co-grafted groups exhibited lower populations of T-cells and activated microglia compared to the groups without SCs. Our results suggest that co-graft of SCs benefit both xeno- and allo-transplantation of VM tissue in a PD rat model. Use of SCs enhanced the survival of the grafted dopaminergic neurons and improved functional recovery. The enhancement may in part be attributable to the immune-modulatory properties of SCs. In addition, [18F]DOPA and [18F]FE-PE2I coupled with PET may provide a feasible method for in vivo evaluation of the functional integrity of the grafted DA cell in parkinsonian rats.

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