scholarly journals Exploratory Studies With BT-11

2016 ◽  
Vol 35 (5) ◽  
pp. 521-529 ◽  
Author(s):  
Philippe Bissel ◽  
Katie Boes ◽  
Jonathan Hinckley ◽  
Bernard S. Jortner ◽  
Geraldine Magnin-Bissel ◽  
...  
Keyword(s):  
Single Dose ◽  
Histopathological Examination ◽  
Clinical Pathology ◽  
Sprague Dawley ◽  
Plasma Enzymes ◽  
Sprague Dawley Rats ◽  
And Control ◽  
Kidney Liver ◽  
Orally Active ◽  
The Brain

Lanthionine synthetase cyclase-like receptor 2 (LANCL2) is a novel therapeutic target for Crohn’s disease (CD). BT-11 is a small molecule that binds LANCL2, is orally active, and has demonstrated therapeutic efficacy in 3 validated mouse models of colitis at doses as low as 8 mg/kg/d. Exploratory experiments evaluated BT-11 in male Harlan Sprague Dawley rats with a single oral dose of 500 mg/kg and 80 mg/kg/d for 14 days (n = 10 rats dosed/group). Treated and control rats were observed for behavioral detriments, and blood and tissues were collected for clinical pathology and histopathological examination. A functional observational battery demonstrated no differences between treated and control groups over multiple times of observation for quantal, categorical, and continuous end points, including posture, in cage activity, approach, response to touch, weight, grip strength, body temperature, and time on a rotarod. Histopathological examination of the brain, kidney, liver, adrenal gland, testes, stomach, small and large intestines, duodenum, pancreas, heart, lungs, spleen, thymus, and rib found no significant differences between the groups. Plasma enzymes associated with liver function were transiently elevated 2 to 4 days after the 500 mg/kg single dose but returned to normal values by 8 days and were not observed at any time in rats given 80 mg/kg/d for 14 days. One hour after oral administration of a single dose of 80 mg/kg, BT-11 had a maximal concentration of 21 ng/mL; the half-life was 3 hours. These experimental results demonstrated that BT-11 is well tolerated in rats, and, with further testing, may hold promise as an orally active therapeutic for CD.

scholarly journals Evaluation of the Single-Dose Toxicity of Capsaicin Pharmacopuncture in Rats

2020 ◽  
Vol 37 (3) ◽  
pp. 167-172 ◽  
Author(s):  
Ji Hye Hwang ◽  
Jaseung Ku ◽  
Chul Jung
Keyword(s):  
Animal Model ◽  
Single Dose ◽  
Saline Solution ◽  
Sprague Dawley ◽  
Control Groups ◽  
Male And Female ◽  
Sprague Dawley Rats ◽  
Body Weights ◽  
And Control ◽  
Safe Dose

Background: This study aimed to assess the toxicity of capsaicin (CP) pharmacopunture in an animal model.<br/>Methods: The toxicity of a single-muscular dose of CP (45.45 mg/mL) was evaluated in 6-week-old male and female Sprague-Dawley rats. A total of 20 rats were assigned to 2 groups which were sex and weight matched. All rats acclimatized for 1 week before receiving 1.0 mL of CP (45.45 mg/mL) or normal saline solution(control) intramuscularly. The general condition and mortality of the animals were observed. The rats were sacrificed 2 weeks after CP was administered and histopathology was performed.<br/>Results: No abnormal symptoms or deaths were observed, and there was no difference in body weights between the CP and control groups throughout the study. No significant differences in histopathology were observed between the groups.<br/>Conclusion: No toxicological changes related to the administration of CP were observed. This study indicated that the safe dose of CP in Sprague-Dawley rats was 1.0 mL of CP (45.45 mg/mL) or less. Further studies are needed to confirm the safety of CP in the human body.

Permeability of the microcirculation in area postrema of rat

1988 ◽  
Vol 46 ◽  
pp. 348-349
Author(s):  
Shams M. Ghoneim ◽  
Frank M. Faraci ◽  
Gary L. Baumbach
Keyword(s):  
Brain Stem ◽  
Area Postrema ◽  
Upper Body ◽  
Sprague Dawley ◽  
Sodium Cacodylate ◽  
Acute Hypertension ◽  
Sprague Dawley Rats ◽  
Ultrastructural Characteristics ◽  
The Brain ◽  
Adjacent Brain

The area postrema is a circumventricular organ in the brain stem and is one of the regions in the brain that lacks a fully functional blood-brain barrier. Recently, we found that disruption of the microcirculation during acute hypertension is greater in area postrema than in the adjacent brain stem. In contrast, hyperosmolar disruption of the microcirculation is greater in brain stem. The objective of this study was to compare ultrastructural characteristics of the microcirculation in area postrema and adjacent brain stem.We studied 5 Sprague-Dawley rats. Horseradish peroxidase was injected intravenously and allowed to circulate for 1, 5 or 15 minutes. Following perfusion of the upper body with 2.25% glutaraldehyde in 0.1 M sodium cacodylate, the brain stem was removed, embedded in agar, and chopped into 50-70 μm sections with a TC-Sorvall tissue chopper. Sections of brain stem were incubated for 1 hour in a solution of 3,3' diaminobenzidine tetrahydrochloride (0.05%) in 0.05M Tris buffer with 1% H2O2.

EFFECT OF EXPERIMENTALLY INDUCED THYROIDITIS ON BIOSYNTHESIS OF THYROXINE IN RATS

1969 ◽  
Vol 62 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Colum A. Gorman ◽  
James W. Anderson ◽  
Eunice V. Flock ◽  
Charles A. Owen ◽  
Khalil G. Wakim
Keyword(s):  
Intravenous Administration ◽  
Hashimoto's Thyroiditis ◽  
Sprague Dawley ◽  
Thyroid Extract ◽  
Histologic Appearance ◽  
Gland Weight ◽  
Sprague Dawley Rats ◽  
Thyroid Glands ◽  
And Control ◽  
Experimentally Induced

ABSTRACT Thyroiditis was induced in Sprague-Dawley rats by repeated immunization with thyroid extract and Freund's adjuvant. Immunized and control animals were killed at intervals up to 6 hours after intravenous administration of 131I as iodide at 5, 8 and 10 weeks after the first injection. Radioiodinated compounds in the thyroid glands were identified chromatographically. Evidence of moderate thyroiditis was present (histologic appearance, gland weight, and protein-bound iodine-butanol-extractable iodine difference) but the rate of incorporation of radioiodide into thyroxine, the percentage of radioactivity in the gland as iodide, and the MIT/DIT ratio were not significantly different in immunized and control animals. The MIT/DIT ratio was found to vary with time after 131I administration in both immunized and control animals. These studies did not uncover a defect in organification of iodide in experimental thyroiditis similar to that described by others in humans with Hashimoto's thyroiditis.

Ultrastructural changes of Basolateral Amygdaloid nuclei in the Sprague Dawley rats brain following exposure to naphthalene balls

2021 ◽  
Vol 12 (2) ◽  
pp. 1272-1275
Author(s):  
Angu Bala Ganesh K S V ◽  
Sujeet Shekhar Sinha ◽  
Kesavi Durairaj ◽  
Abdul Sahabudeen K
Keyword(s):  
Structural Changes ◽  
Corn Oil ◽  
Chromatin Condensation ◽  
Ultrastructural Changes ◽  
High Dose ◽  
Model Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
The Brain ◽  
Amygdaloid Nuclei

Naphthalene is a bicyclic aromatic constituent commonly used in different domestic and marketable applications comprising soil fumigants, lavatory scent disks and mothballs. Accidentally, workers, children and animals are exposed to naphthalene mothballs, so there is a need to study the pathology behind this chemical toxicity. The current study was carried out to assess the ultra structural changes of basolateral amygdaloid nuclei in the Sprague Dawley rats brain in association to naphthalene toxicity. The toxicity model group was administered with naphthalene (200 and 400mg) using corn oil as a vehicle for 28 days. The post delayed toxicity of naphthalene high dose ingestion was also assessed in rats. After the experimental period, the brain tissue was processed to observe the ultra structural changes using a transmission electron microscope. The alterations in cell organelles, nuclei damage, mitochondrial swelling, chromatin condensation suggested naphthalene induced damage in the neurons of the basolateral amygdala of the brain in the toxicity model group. These experimental trials provide information about the alert of mothball usage in the home and identify risks linked with accidental exposure and misuse.

scholarly journals Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats

2014 ◽  
Vol 40 (4) ◽  
pp. 421-424 ◽  
Author(s):  
Igor Bastos Polonio ◽  
Milena Marques Pagliareli Acencio ◽  
Rogério Pazetti ◽  
Francine Maria de Almeida ◽  
Bárbara Soares da Silva ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Experimental Model ◽  
Ventricular Hypertrophy ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Sprague Dawley ◽  
Control Groups ◽  
Right Heart ◽  
Sprague Dawley Rats ◽  
And Control

We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation.

scholarly journals Synergistic suppression of pre-perfusion of donor livers with recipient serum and cobra venom factor treatment on hyperacute rejection following liver xenotransplantation

2012 ◽  
Vol 27 (5) ◽  
pp. 301-305 ◽  
Author(s):  
Baohua Zhu ◽  
Chuanming Tong ◽  
Weitao Guo ◽  
Rong Pu ◽  
Guoping Zhang ◽  
...  
Keyword(s):  
Survival Time ◽  
Hyperacute Rejection ◽  
Cobra Venom ◽  
Control Group ◽  
Sprague Dawley ◽  
Donor Liver ◽  
Cobra Venom Factor ◽  
Sd Rats ◽  
Sprague Dawley Rats ◽  
And Control

PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.

Changes in total body calcium balance with exercise in the rat

1983 ◽  
Vol 55 (1) ◽  
pp. 201-204 ◽  
Author(s):  
A. D. LeBlanc ◽  
H. J. Evans ◽  
P. C. Johnson ◽  
S. Jhingran
Keyword(s):  
Least Squares ◽  
Voluntary Exercise ◽  
Calcium Balance ◽  
Sprague Dawley ◽  
Total Body Calcium ◽  
Sprague Dawley Rats ◽  
Least Squares Fit ◽  
Significant Change ◽  
Total Body ◽  
And Control

The purpose of this study was to evaluate the effect of deconditioning on the total body calcium in rats. Two separate experiments were performed using female Sprague-Dawley rats, 187-266 days of age. Total body calcium was measured in experimental and control rats during and following several weeks of voluntary exercise. The slope from the least-squares fit of total body calcium with time was used to obtain an average calcium balance for each animal during each study period. In both groups the exercised rats had a significantly decreased calcium balance after cessation of exercise, whereas no significant change was seen in nonexercised controls. In both groups, the exercised animals gained calcium at a significantly greater rate than controls. Our findings indicate that while exercised rats may gain calcium at a faster rate compared with nonexercising controls, the rate of gain following cessation of exercise is less than the controls.

scholarly journals TRANSFERSOME GEL FORMULATION OF AN ETHANOL EXTRACT OF APPLES (MALUS DOMESTICA MILL) CONTAINING ANTIOXIDANTS AND IN VITRO PENETRATION TESTING USING FRANZ DIFFUSION CELLS

2017 ◽  
Vol 9 ◽  
pp. 32 ◽  
Author(s):  
Nurarita Fadila Zesiorani ◽  
Effionora Anwar
Keyword(s):  
Ethanol Extract ◽  
Sprague Dawley ◽  
Diffusion Cells ◽  
Sprague Dawley Rats ◽  
Apple Peel ◽  
Franz Diffusion Cells ◽  
Drug Efficiency ◽  
And Control ◽  
Peel Extract

Objective: This study aims to formulate and characterize a transfersome apple peel extract, formulate it into a gel, and compare it with a control gelmade without transfersome.Methods: Both gels were evaluated, stability tested, and penetration tested using Franz diffusion cells on the skin of female Sprague-Dawley rats. Thetransfersome preparations were formulated with different concentrations of the active substance, quercetin: 0.5% (F1); 0.7% (F2), and 1.0% (F3).Results: Based on the characterization results, F1 was selected as the optimum gel formulation because it had spherical morphology, a Dmean volume of106.44±2.70 nm, a polydispersity index of 0.078±0.01, a zeta potential of −49.96±2.05 mV, and a drug efficiency entrapment percentage of 78.78±0.46%.The cumulative amount of quercetin that was penetrated with the transfersome gel was 1514.41±26.31 μg/cm2, whereas the penetration with thecontrol gel extract was 1133.62±18.96 μg/cm2. The cumulative percentages of the penetrated gel transfersome and gel extract were 78.40±1.89%and 49.89±0.88%, respectively. The fluxes of transfersome gel and control gel extract were 52.33±0.11 μg/cm²/hrs and 40.89±0.68 μg/cm²/hrs,respectively.Conclusions: Based on these results, it can be concluded that the gel with transfersome exhibited better penetration than the gel extract alone.

The organum vasculosum laminae terminalis in immune-to-brain febrigenic signaling: a reappraisal of lesion experiments

2003 ◽  
Vol 285 (2) ◽  
pp. R420-R428 ◽  
Author(s):  
Andrej A. Romanovsky ◽  
Naotoshi Sugimoto ◽  
Christopher T. Simons ◽  
William S. Hunter
Keyword(s):  
Side Effects ◽  
Isotonic Saline ◽  
Alternative Interpretation ◽  
Sprague Dawley ◽  
Febrile Response ◽  
Drinking Response ◽  
Organum Vasculosum Laminae Terminalis ◽  
Sprague Dawley Rats ◽  
Organum Vasculosum ◽  
The Brain

The organum vasculosum laminae terminalis (OVLT) has been proposed to serve as the interface for blood-to-brain febrigenic signaling, because ablation of this structure affects the febrile response. However, lesioning the OVLT causes many “side effects” not fully accounted for in the fever literature. By placing OVLT-lesioned rats on intensive rehydration therapy, we attempted to prevent these side effects and to evaluate the febrile response in their absence. After the OVLT of Sprague-Dawley rats was lesioned electrolytically, the rats were given access to 5% sucrose for 1 wk to stimulate drinking. Sucrose consumption and body mass were monitored. The animals were examined twice a day for signs of dehydration and treated with isotonic saline (50 ml/kg sc) when indicated. This protocol eliminated mortality but not several acute and chronic side effects stemming from the lesion. The acute effects included adipsia and gross (14% of body weight) emaciation; chronic effects included hypernatremia, hyperosmolality, a suppressed drinking response to hypertonic saline, and previously unrecognized marked (by ∼2°C) and long-lasting (>3 wk) hyperthermia. Because the hyperthermia was not accompanied by tail skin vasoconstriction, it likely reflected increased thermogenesis. After the rats recovered from the acute (but not chronic) side effects, their febrile response to IL-1β (500 ng/kg iv) was tested. The sham-operated rats developed typical monophasic fevers (∼0.5°C), the lesioned rats did not. However, the absence of the febrile response in the OVLT-lesioned rats likely resulted from the untreatable side effects. For example, hyperthermia at the time of pyrogen injection was high enough (39–40°C) to solely prevent fever from developing. Hence, the changed febrile responsiveness of OVLT-lesioned animals is given an alternative interpretation, unrelated to febrigenic signaling to the brain.

scholarly journals Quantitative Analysis of Diffusion Tensor Imaging in Chronic Hepatitis in Rats

2020 ◽  
Author(s):  
Mengping Huang ◽  
Xin Lu ◽  
Xiaofeng Wang ◽  
Jian Shu
Keyword(s):  
Chronic Hepatitis ◽  
Diffusion Tensor Imaging ◽  
Liver Fibrosis ◽  
Diffusion Tensor ◽  
Control Group ◽  
Sprague Dawley ◽  
Subcutaneous Injections ◽  
Sprague Dawley Rats ◽  
Pathological Stages ◽  
The Brain

Abstract Background Diffusion tensor imaging (DTI) is mainly used for detecting white matter fiber in the brain. From this, DTI has been applied to assess fiber in liver disorders by prior studies. But non-sufficient data has been obtained if DTI could be used for exactly staging chronic hepatitis. This study is to assess the value of DTI for staging of liver fibrosis (F), necroinflammatory activity (A), and steatosis (S) of chronic hepatitis in rats. Methods Seventy male Sprague-Dawley rats were divided into control group(n = 10) and experimental group(n = 60). The rat models of chronic hepatitis were established by abdominal subcutaneous injections of 40% CCl4. All rats underwent 3.0T MRI. ROIs were placed on DTI to estimate MR parameters (rADC value and FA value). Histopathology was the reference standard. Multiple linear regression was used to analyze the association between MR parameters and pathology. The differences in rADC value and FA value among pathological stages were evaluated by MANOVA or ANOVA. LSD was used to test the differences between each two groups. ROC analysis was performed. Results The numbers of each pathology were as follows: F0(n = 15), F1(n = 11), F2(n = 6), F3(n = 9), F4(n = 6); A0(n = 8), A1(n = 16), A2(n = 16), A3(n = 7); S0(n = 10), S1(n = 7), S2(n = 3), S3(n = 11), S4(n = 16). The rADC value had a negative correlation with liver fibrosis (r=-0.392, P = 0.008) and inflammation (r=-0.359, P = 0.015). FA value had a positive correlation with fibrosis (r = 0.409, P = 0.005). Significant differences were found in FA value between F4 and F0 ~ F3 (P = 0.03), while no significant differences among F0 ~ F3 were found (P > 0.05). AUC of FA value in differentiating F4 from F0 ~ F3 was 0.909(p < 0.001) with 83.3% Sensitivity, 85.4% specificity when the FA value was at the cut-off of 588.089(× 10− 6mm2/s). Conclusion FA value for DTI can distinguish early cirrhosis from normal, mild and moderate liver fibrosis.

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