scholarly journals A Novel Strategy to Enhance Microfracture Treatment With Stromal Cell-Derived Factor-1 in a Rat Model

2021 ◽  
Vol 8 ◽  
Author(s):  
Taylor Mustapich ◽  
John Schwartz ◽  
Pablo Palacios ◽  
Haixiang Liang ◽  
Nicholas Sgaglione ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cartilage Repair ◽  
Osteochondral Defect ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Stromal Cell Derived Factor ◽  
Empty Control

BackgroundMicrofracture is one of the most widely used techniques for the repair of articular cartilage. However, microfracture often results in filling of the chondral defect with fibrocartilage, which exhibits poor durability and sub-optimal mechanical properties. Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for mesenchymal stem cells (MSCs) and is expressed at high levels in bone marrow adjacent to developing cartilage during endochondral bone formation. Integrating SDF-1 into an implantable collagen scaffold may provide a chondro-conductive and chondro-inductive milieu via chemotaxis of MSCs and promotion of chondrogenic differentiation, facilitating more robust hyaline cartilage formation following microfracture.ObjectiveThis work aimed to confirm the chemoattractive properties of SDF-1 in vitro and develop a one-step method for incorporating SDF-1 in vivo to enhance cartilage repair using a rat osteochondral defect model.MethodsBone marrow-derived MSCs (BMSCs) were harvested from the femurs of Sprague–Dawley rats and cultured in low-glucose Dulbecco’s modified Eagle’s medium containing 10% fetal bovine serum, with the medium changed every 3 days. Passage 1 MSCs were analyzed by flow cytometry with an S3 Cell Sorter (Bio-Rad). In vitro cell migration assays were performed on MSCs by labeling cells with carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE; Bio-Rad). For the microfracture model, a 1.6-mm-diameter osteochondral defect was created in the femoral trochleae of 20 Sprague–Dawley rats bilaterally until bone marrow spillage was seen under saline irrigation. One knee was chosen at random to receive implantation of the scaffold, and the contralateral knee was left unfilled as an empty control. Type I collagen scaffolds (Kensey Nash) were coated with either gelatin only or gelatin and SDF-1 using a dip coating process. The rats received implantation of either a gelatin-only scaffold (N = 10) or gelatin-and-SDF-1 scaffold (N = 10) at the site of the microfracture. Femurs were collected for histological analyses at 4- and 8-week time points post-operatively, and sections were stained with Safranin O/Fast Green. The samples were graded blindly by two observers using the Modified O’Driscoll score, a validated scoring system for chondral repair. A minimum of 10 separate grading scores were made per sample and averaged. Quantitative comparisons of cell migration in vitro were performed with one-way ANOVA. Cartilage repair in vivo was also compared among groups with one-way ANOVA, and the results were presented as mean ± standard deviation, with P-values < 0.05 considered as statistically significant.ResultsMSC migration showed a dose–response relationship with SDF-1, with an optimal dosage for chemotaxis between 10 and 100 ng/ml. After scaffold implantation, the SDF-1-treated group demonstrated complete filling of the cartilage defect with mature cartilage tissue, exhibiting strong proteoglycan content, smooth borders, and good incorporation into marginal cartilage. Modified O’Driscoll scores after 8 weeks showed a significant improvement of cartilage repair in the SDF-1 group relative to the empty control group (P < 0.01), with a trend toward improvement when compared with the gelatin-only-scaffold group (P < 0.1). No significant differences in scores were found between the empty defect group and gelatin-only group.ConclusionIn this study, we demonstrated a simple method for improving the quality of cartilage defect repair in a rat model of microfracture. We confirmed the chemotactic properties of SDF-1 on rat MSCs and found an optimized dosage range for chemotaxis between 10 and 100 ng/ml. Furthermore, we demonstrated a strategy to incorporate SDF-1 into gelatin–collagen I scaffolds in vivo at the site of an osteochondral defect. SDF-1-treated defects displayed robust hyaline cartilage resurfacing of the defect with minimal fibrous tissue, in contrast to the empty control group. The results of the in vitro and in vivo studies together suggest that SDF-1-mediated signaling may significantly improve the quality of cartilage regeneration in an osteochondral defect.

Cytochrome C suppresses renal accumulation and nephrotoxicity of polymyxin B

2018 ◽  
Vol 38 (2) ◽  
pp. 193-200 ◽  
Author(s):  
Z-D Li ◽  
J Luo ◽  
L-H Jia ◽  
X-Y Wang ◽  
Z-K Xun ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Polymyxin B ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
C 30 ◽  
C 50

The receptor megalin plays an important role in the accumulation of polymyxin B (PMB) in renal cells in vitro. This study aimed to examine the effects of cytochrome c (cyto c), a typical megalin ligand, on renal accumulation and nephrotoxicity of PMB in vivo. Thirty Sprague-Dawley rats were randomly divided into the vehicle control group, PMB group, PMB + cyto c 50, 100, or 200 mg/kg group, respectively, and were treated with intravenous cyto c 30 min before the administration of PMB 4.0 mg/kg once a day for consecutive 5 days. On the 4th day after administration, 24 h urine was collected to determine N-acetyl-β-D-glucosaminidase excretion. Six hours after the last injection on the 5th day, kidneys were harvested to assay PMB concentration and observe pathological alterations, and blood samples were collected to assay serum creatinine (SCr), blood urea nitrogen (BUN), and blood β2-microglobulin (β2-MG) levels. Cyto c 50, 100, and 200 mg/kg decreased the accumulation of PMB in the kidney by 18.5%, 39.1% ( p < 0.01), and 36.8% ( p < 0.01), respectively, and reduced 24 h N-acetyl-β-D- glucosaminidase excretion by 22.5% ( p < 0.05), 40.4% ( p < 0.01), and 40.4% ( p < 0.01), respectively. Kidney pathological damage induced by PMB was markedly reduced by cyto c 100 mg/kg and 200 mg/kg. However, there were no significant differences in SCr, BUN, and blood β2-MG levels among the groups. These results indicated that cyto c may inhibit the renal accumulation and nephrotoxicity of PMB in a rat model, further proving the role of megalin in the accumulation of PMB.

Aptamer-Functionalized Bioscaffold Enhances Cartilage Repair by Improving Stem Cell Recruitment in Osteochondral Defects of Rabbit Knees

2019 ◽  
Vol 47 (10) ◽  
pp. 2316-2326 ◽  
Author(s):  
Xin Wang ◽  
Xiongbo Song ◽  
Tao Li ◽  
Jiajia Chen ◽  
Guotao Cheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Silk Fibroin ◽  
Cartilage Repair ◽  
Osteochondral Defect ◽  
Cartilage Tissue ◽  
Control Group ◽  
Osteochondral Defects ◽  
Scaffold Group

Background: Recruitment of endogenous stem cells has been considered an alternative to cell injection/implantation in articular cartilage repair. Purpose: (1) To develop a cartilage tissue-engineering scaffold with clinically available biomaterials and functionalize the scaffold with an aptamer (Apt19s) that specifically recognizes pluripotent stem cells. (2) To determine whether this scaffold could recruit joint-resident mesenchymal stem cells (MSCs) when implanted into an osteochondral defect in a rabbit model and to examine the effects of cartilage regeneration. Study Design: Controlled laboratory study. Methods: The reinforced scaffold was fabricated by embedding a silk fibroin sponge into silk fibroin/hyaluronic acid–tyramine hydrogel and characterized in vitro. A cylindrical osteochondral defect (3.2 mm wide × 4 mm deep) was created in the trochlear grooves of rabbit knees. The rabbits were randomly assigned into 3 groups: Apt19s-functionalized scaffold group, scaffold-only group, and control group. Animals were sacrificed at 6 and 12 weeks after transplantation. Repaired tissues were evaluated via gross examination, histologic examination, and immunohistochemistry. Results: In vitro, this aptamer-functionalized scaffold could recruit bone marrow–derived MSCs and support cell adhesion. In vivo, the aptamer-functionalized scaffold enhanced cell homing in comparison with the aptamer-free scaffold. The aptamer-functionalized scaffold group also exhibited superior cartilage restoration when compared with the scaffold-only group and the control group. Conclusion: The Apt19s-functionalized scaffold exhibited the ability to recruit MSCs both in vitro and in vivo and achieved a better outcome of cartilage repair than the scaffold only or control in an osteochondral defect model. Clinical Relevance: The findings demonstrate a promising strategy of using aptamer-functionalized bioscaffolds for restoration of chondral/osteochondral defects via aptamer-introduced homing of MSCs.

scholarly journals Leptin induces the expression of tumorigenic genes in the gastric mucosa of male Sprague-Dawley rats

2018 ◽  
Vol 243 (14) ◽  
pp. 1118-1124 ◽  
Author(s):  
Faizatul Isyraqiah ◽  
Methil K Kutty ◽  
Damayanthi Durairajanayagam ◽  
Norita Salim ◽  
Harbindarjeet Singh
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Gastric Carcinogenesis ◽  
Control Group ◽  
Sprague Dawley ◽  
Gastric Cancer Cells ◽  
Sprague Dawley Rats

Leptin promotes the growth of gastric cancer cells in vitro. It is, however, unknown if leptin induces gastric cancer in vivo. This study therefore investigated the effect of leptin on the histology and expression of tumorigenic genes in the stomach of rats following 40 weeks of leptin treatment. Male Sprague-Dawley rats, aged 6 weeks, were randomized into control and experimental groups ( n = 8 per group). The experimental group was given intraperitoneal injections of leptin (60 µg/kg/day) once daily for 40 weeks, whereas the control group received intraperitoneal injection of an equal volume of normal saline daily. Rats were housed in polypropylene cages for the duration of the study. Body weight was measured weekly. Upon completion of treatment, rats were euthanized and their stomachs were collected for histopathological examination, microarray, and RT-qPCR. Data were analyzed using one-way ANOVA and Fisher’s exact test. On histology, one rat (12.5%) in the leptin-treated group had a large red-colored tumor nodule at the pyloric antrum of the stomach. Microscopically, stomachs of two leptin-treated rats (25%) showed hyperplasia or dysplasia. Microarray analysis revealed significant upregulation of a number of genes in the stomachs of leptin-treated rats that have been shown to be associated with tumorigenesis in other tissues, including Furin (protein maturation), Eef1a1 and Eif4g2 (translation factors), Tmed2 (vesicular trafficking), Rab7a (plasma membrane trafficking), Rfwd2 (protein degradation), Fth1 and Ftl1 (oxygen transport), Tspan8, Tspan1, Fxyd3, and Rack1 (cell migration), Pde4d (signal transduction), Nupr1 and Ybx1 (transcription factors), Ptma and Tmem134 (oncogenes), Srsf2 (mRNA maturation), and Reep5 (cell proliferation). None of the known oncogenes were, however, significantly up-regulated. In conclusion, although the overall effect of leptin on gastric carcinogenesis seems inconclusive, the findings of dysplasia and the up-regulation of some of the cancer-related genes nevertheless warrant further scrutiny on the role of leptin in gastric cancer. Impact statement Gastric cancer is the third most common cause of death due to cancer in the world. Obese individuals are at risk of developing gastric cancer, and the reason for this is unknown. Serum leptin levels are high in obese individuals and leptin is known to induce proliferation of gastric cancer cells in vitro. However, to date, no reports exist on the tumorigenic effects of leptin on the stomach in vivo. This study therefore determines if chronic leptin administration induces gastric carcinogenesis in non-obese rats, which might serve as a useful animal model for future studies. Although the findings are somewhat inconclusive, to our knowledge, however, this is the first study to show the up-regulation of numerous potential driver genes that highlight the potential role of leptin in the higher prevalence of gastric cancer among obese individuals. The findings certainly necessitate further scrutiny of leptin gastric cancer.

scholarly journals Pharmacological comparison of four biopolymeric natural gums as hemostatic agents for management of bleeding wounds: preliminary in vitro and in vivo results

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Himanshu Kushwah ◽  
Nidhi Sandal ◽  
Meenakshi Chauhan ◽  
Gaurav Mittal
Keyword(s):  
Xanthan Gum ◽  
Guar Gum ◽  
Human Lymphocytes ◽  
Sprague Dawley ◽  
Gum Tragacanth ◽  
Civilian Trauma ◽  
Sprague Dawley Rats ◽  
Cytotoxicity Studies

Abstract Background Uncontrolled bleeding is one of the primary reasons for preventable death in both civilian trauma and military battle field. This study evaluates in vitro and in vivo hemostatic potential of four biopolymeric natural gums, namely, gum tragacanth, guar gum, xanthan gum, and gum acacia. In vitro evaluation of whole blood clotting time and erythrocyte agglutination assay were carried out. In vitro cytotoxicity studies with respect to each gum were done in human lymphocytes to ascertain percent cell viability. In vivo hemostatic potential of each gum (as sponge dressing and powder form) was evaluated in Sprague Dawley rats using tail bleeding assay and compared with commercially available hemostatic sponge. Other important parameters like (a) time taken for complete hemostasis, (b) amount of blood absorbed, (c) adherence strength of developed hemostatic dressing(s), (d) incidence of re-bleeding, and (e) survival of animals were also studied. Results Of the four test gums studied, xanthan gum (@3mg/ml of blood) and gum tragacanth (@35mg/ml of blood) were able to clot blood in least time (58.75±6.408 s and 59.00±2.082 s, respectively) and exhibited very good hemostatic potential in vitro. Except for xanthan gum, all other test gums did not exhibit any significant cytotoxicity at different time points till 24 h. In rat tail bleeding experiments, gum tragacanth sponge dressing and powder achieved hemostasis in least time (156.2±12.86 s and 76±12.55 s, respectively) and much earlier than commercially available product (333.3±38.84 s; p˂0.01). Conclusion Results indicate potential of gum tragacanth to be developed into a suitable hemostatic product.

Bioavailability in Vivo of Benzo[a]Pyrene Adsorbed to Diesel Particulate

1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio
Keyword(s):  
Health Risks ◽  
Quantitative Description ◽  
Intratracheal Instillation ◽  
Direct Analysis ◽  
Sprague Dawley ◽  
Reasonable Estimate ◽  
Diesel Particulate ◽  
Sprague Dawley Rats

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.

scholarly journals Regulation of mdrlb gene expression in Fischer, Wistar and Sprague-Dawley rats in vivo and in vitro

1996 ◽  
Vol 17 (3) ◽  
pp. 451-457 ◽  
Author(s):  
Barbara A. Hill ◽  
Paul C. Brown ◽  
Karl-Heinz Preisegger ◽  
Jeffrey A. Silverman
Keyword(s):  
Gene Expression ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

SYNTHESIS OF DNA AND LECITHIN IN TISSUE CULTURE AND OESTROGEN RECEPTOR ACTIVITY IN RAT MAMMARY TUMOURS DEPENDENT ON AND INDEPENDENT OF THE OVARY

1979 ◽  
Vol 81 (2) ◽  
pp. 183-198 ◽  
Author(s):  
ANNE-MARIE SCOTT ◽  
SUSAN MURPHY ◽  
R. A. HAWKINS
Keyword(s):  
Tissue Culture ◽  
Dna Synthesis ◽  
Oestrogen Receptor ◽  
Receptor Activity ◽  
Sprague Dawley ◽  
Mammary Tumours ◽  
Sprague Dawley Rats ◽  
The Media

Dimethylbenz(a)anthracene (DMBA)-induced and transplanted rat mammary tumours (2 lines) were examined for oestrogen receptor activity, and for sensitivity to hormones in vivo (by ovariectomy) and in vitro (by tissue culture). In vivo, the growth of all tumours induced by the administration of DMBA in random-bred Sprague–Dawley rats was found to be dependent on the ovary, whilst in all transplanted tumours (12 TG-3 and six TG-5 lines), maintained in an inbred strain of Sprague–Dawley rats, growth was found to be independent of the ovary. In vitro, the capacity for DNA synthesis in DMBA-induced tumours was better maintained after 24 h when insulin (10 μg/ml) and corticosterone (5 μg/ml) or insulin, corticosterone and prolactin (each 5 μg/ml) were present in the medium (five out of 12 and eight out of 11 tumours respectively); no effect of hormones in the media was detected after 48 h. In the transplanted tumours, no effect of hormones on DNA synthesis was detected after either 24 or 48 h of culture. Synthesis of lecithin was not detectably influenced by the presence of hormones in either DMBA-induced or transplanted tumours. Oestrogen receptor concentrations were, on average, significantly higher in the DMBA-induced tumours than in either line of transplanted tumour. For 22 DMBA-induced tumours and 15 transplanted tumours, the effect of hormones in vitro (`response') was directly correlated with receptor concentration at time 0 (Spearman's ρ = + 0·59) and inversely correlated with the rate of DNA synthesis (`basal') at time 0 (Spearman's ρ = −0·62). No single parameter or pair of parameters permitted accurate distinction between the tumour types.

scholarly journals Chronic Microcystin-LR Exposure Induces Hepatocarcinogenesis via Increased Gankyrin in Vitro and in Vivo

2018 ◽  
Vol 49 (4) ◽  
pp. 1420-1430 ◽  
Author(s):  
Lixiong He ◽  
Yujing Huang ◽  
Qiaonan Guo ◽  
Hui Zeng ◽  
Chuanfen Zheng ◽  
...  
Keyword(s):  
Low Dose ◽  
Soft Agar ◽  
Tumor Formation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
L02 Cells ◽  
Insight Into

Background/Aims: Our recent study indicated that the serum microcystin-LR (MC-LR) level is positively linked to the risk of human hepatocellular carcinoma (HCC). Gankyrin is over-expressed in cancers and mediates oncogenesis; however, whether MC-LR induces tumor formation and the role of gankyrin in this process is unclear. Methods: We induced malignant transformation of L02 liver cells via 35 passages with exposure to 1, 10, or 100 nM MC-LR. Wound healing, plate and soft agar colony counts, and nude mice tumor formation were used to evaluate the tumorigenic phenotype of MC-LR-treated cells. Silencing gankyrin was used to confirm its function. We established a 35-week MC-LR exposure rat model by twice weekly intraperitoneal injection with 10 μg/kg body weight. In addition, 96 HCC patients were tested for tumor tissue gankyrin expression and serum MC-LR levels. Results: Chronic low-dose MC-LR exposure increased proliferation, mobility, clone and tumor formation abilities of L02 cells as a result of gankyrin activation, while silencing gankyrin inhibited the carcinogenic phenotype of MC-LR-treated cells. MC-LR also induced neoplastic liver lesions in Sprague-Dawley rats due to up-regulated gankyrin. Furthermore, a trend of increased gankyrin was observed in humans exposed to MC-LR. Conclusion: These results suggest that MC-LR induces hepatocarcinogenesis in vitro and in vivo by increasing gankyrin levels, providing new insight into MC-LR carcinogenicity studies.

Inhibitory Effect of Resveratrol on the Pharmacokinetics of Ticagrelor in Vivo and Vitro

2021 ◽  
Author(s):  
Peng Wang ◽  
Xiao-Xia Hu ◽  
Ying-hui Li ◽  
Nan-Yong Gao ◽  
Guo-quan Chen ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Control Group ◽  
Rat Liver Microsomes ◽  
Sprague Dawley ◽  
Group B

This study was to evaluate the effect of resveratrol on the pharmacokinetics of ticagrelor in rats and the metabolism of ticagrelor in human CYP3A4 and liver microsomes. Eighteen Sprague-Dawley rats were randomly divided into three groups: group A (control group), group B (50mg/kg resveratrol), and group C (150mg/kg resveratrol ). After 30 minutes administration of resveratrol, a single dose of ticagrelor (18mg/kg) was administered orally. The vitro experiment was performed to examine the influence of resveratrol on ticagrelor metabolism in CYP3A4*1, human, and rat liver microsomes. Serial biological samples were assayed by validated UHPLC-MS/MS methods. In vivo study, the AUC and Cmax of ticagrelor in group B and C appeared to be significantly higher than the control group, while Vz/F and CLz/F of ticagrelor in group B and C were significantly decreased. In vitro study, resveratrol exhibited an inhibitory effect on CYP3A4*1, human and rat liver microsomes. The IC50 values of resveratrol were 56.75μM，69.07μM and 14.22μM, respectively. Our results indicated that resveratrol had a inhibitory effect on the metabolism of ticagrelor in vitro and vivo. It should be paid more attention to the clinical combination of resveratrol with ticagrelor and ticagrelor plasma concentration should be monitored to avoid the occurrence of adverse reaction.

Comparative studies on tryptophan binding to hepatic nuclear envelopes in Sprague-Dawley and Lewis rats

1994 ◽  
Vol 267 (2) ◽  
pp. R502-R507 ◽  
Author(s):  
H. Sidransky ◽  
E. Verney
Keyword(s):  
Inflammatory Diseases ◽  
Specific Binding ◽  
Quantitative Difference ◽  
Sprague Dawley ◽  
Lewis Rats ◽  
Sprague Dawley Rats ◽  
Nuclear Rna ◽  
Eosinophilia Myalgia Syndrome

Since Lewis rats are susceptible to many inflammatory diseases and have been used in an experimental model of the eosinophilia-myalgia syndrome, we investigated whether Lewis rats would respond to L-tryptophan as have Sprague-Dawley rats reported earlier. In this comparative study using females of both strains, we observed a decrease in the affinity of in vitro L-tryptophan binding to hepatic nuclei and nuclear envelopes of Lewis rats compared with Sprague-Dawley rats. However, in vivo stimulatory effects of administering L-tryptophan on hepatic polyribosomal aggregation, protein synthesis, and nuclear RNA release were similar in both strains. In vitro [3H]tryptophan binding to hepatic nuclear envelopes, using L-tryptophan implicated in cases of the eosinophilia-myalgia syndrome, revealed less specific binding than when using nonimplicated L-tryptophan in both strains. The possible significance of the quantitative difference in the binding affinity of L-tryptophan to hepatic nuclei of Lewis rats compared with those of Sprague-Dawley rats is as yet undetermined.

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