scholarly journals Therapeutic Effect of Combining Anisodamine With Neostigmine on Local Scar Formation Following Roux-en-Y Choledochojejunostomy in a Novel Rat Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Shao-cheng Lyu ◽  
Jing Wang ◽  
Wen-li Xu ◽  
Han-xuan Wang ◽  
Fei Pan ◽  
...  

Background: The present study aimed to explore the potential effect of combining anisodamine with neostigmine on local scar formation following Roux-en-Y choledochojejunostomy (RCJS) in a novel rat model.Methods: The biliary obstruction model of Sprague Dawley (SD) rats was established in advance, and 54 rats were divided into nine groups randomly (sham operation group, anisodamine group, neostigmine group, combination group, and control group). Anisodamine (25 mg/kg) and neostigmine (50 μg/kg) were injected to the abdominal cavity separately or simultaneously for 1 week since the first day after surgery according to their allocated intervention, while the same amount of saline (0.5 ml) was injected intraperitoneally in the control group. Indexes including body weight, the diameter of the common bile duct, liver function, inflammatory indexes, and the condition of scar formation in different groups at certain time were evaluated in our study.Results: Recovery of liver function (ALT, AST, TB, DB, and GGT) and systematic inflammation indexes (CRP, TNF-α, and IL-1β) in the combination group was prior to that in the control group (p < 0.05), while no statistical difference in the serum level of IL-10 was observed among groups. Rats in the combination group represented a wider anastomotic diameter and lower expression of α-SMA and TGF-β1 at anastomotic stoma compared to the control group (p < 0.05). Histopathological staining showed slighter proliferation of collagen and smooth muscle fibers in rats’ bile duct wall and less local scar formation at anastomotic stoma compared to the control group.Conclusion: The combination of anisodamine and neostigmine can alleviate local and systemic inflammatory response, promote the recovery of liver function, and reduce scar formation in rats after the RCJS procedure.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meng-yu Zhang ◽  
Jie-ping Wang ◽  
Kai He ◽  
Xian-ming Xia

AbstractDevelop a rat model of hilar cholangiocarcinoma for detecting bile salt export pump (Bsep) expression in hilar cholangiocarcinoma tissues, in order to provide a new therapeutic target for the gene therapy of hilar cholangiocarcinoma. Sixty male Wistar rats (body weight, 190 ± 8 g) were randomly divided into three groups (the experimental group, the control group and the sham operation group, n = 20 each) as follows: The three groups were fed a standard diet, the experimental group was injected by cholangiocarcinoma QBC939 cell suspension along the hilar bile duct into the bile duct bifurcation with microsyringe, the control group was injected by normal saline, the sham operation group did not inject anything. Every day assess the rats’ mental state, diet, and motion by using Basso–Beattie–Bresnahan and combined behavioral score. At 4 weeks, one rat of the experimental group was sacrificed after it was administered anesthesia, and we recorded changes in hilar bile duct size, texture, and form. This procedure was repeated at 6 weeks. After 6 weeks, hilar cholangiocarcinoma developed only in the experimental group, thereby establishing an experimental model for studying QBC939-induced hilar cholangiocarcinoma. Tumor formation was confirmed by pathological examination, and hilar bile duct tissues were harvested from both the groups. A real-time polymerase chain reaction assay and an immunohistochemical assay were used to analyze the expression of Bsep in hilar bile duct tissues of each group. From the second week, the rats in experimental group began to eat less, and their body mass decreased compared with control group and sham operation group. After 6 weeks, we detected hilar cholangiocarcinoma in the hilar bile duct tissues of 18 rats (90%) in the experimental group. In the experimental group with hilar cholangiocarcinoma, we found that the levels of total cholesterol, total bilirubin, and direct bilirubin were higher compared with those in the control group and sham operation group. Simultaneously, muddy stones emerged from the bile ducts of rats in the experimental group. The Bsep/Gapdh mRNA ratio in hilar cholangiocarcinoma, control group and sham operation group differed markedly. Light microscopy revealed a granular pattern of Bsep protein expression which reacted with the anti-Bsep antibody. Each section was randomly divided into six regions, with 80 cells were observed in every region. Sections with > 10% positive cells were designated positive, Sections with < 10% positive cells were designated negative. Each group included 4800 cells. In the experimental group, 1200 cells (25%) were positive, in the control group, 3648 cells (76%) were positive and in the sham operation group 3598 cells (75%) were positive, and this difference was statistically significant. Bsep expression significantly decreased in hilar cholangiocarcinoma of rats than those in control group and sham operation group, suggesting that drugs targeting Bsep are a new strategy for hilar cholangiocarcinoma.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiangfeng Liu ◽  
Huijun Kang ◽  
Jiangfeng Lu ◽  
Yike Dai ◽  
Fei Wang

Abstract Background Poor osseointegration is the key reason for implant failure after arthroplasty,whether under osteoporotic or normal bone conditions. To date, osseointegration remains a major challenge. Recent studies have shown that deferoxamine (DFO) can accelerate osteogenesis by activating the hypoxia signaling pathway. The purpose of this study was to test the following hypothesis: after knee replacement, intra-articular injection of DFO will promote osteogenesis and osseointegration with a 3D printed titanium prosthesis in the bones of osteoporotic rats. Materials and methods Ninety female Sprague–Dawley rats were used for the experiment. Ten rats were used to confirm the successful establishment of the osteoporosis model: five rats in the sham operation group and five rats in the ovariectomy group. After ovariectomy and knee arthroplasty were performed, the remaining 80 rats were randomly divided into DFO and control groups (n = 40 per group). The two groups were treated by intraarticular injection of DFO and saline respectively. After 2 weeks, polymerase chain reaction (PCR) and immunohistochemistry were used to evaluate the levels of HIF-1a, VEGF, and CD31. HIF-1a and VEGF have been shown to promote angiogenesis and bone regeneration, and CD31 is an important marker of angiogenesis. After 12 weeks, the specimens were examined by micro-computed tomography (micro-CT), biomechanics, and histopathology to evaluate osteogenesis and osseointegration. Results The results of PCR showed that the mRNA levels of VEGF and CD31 in the DFO group were significantly higher than those in the control group. The immunohistochemistry results indicated that positive cell expression of HIF-1a, VEGF, and CD31 in the DFO group was also higher. Compared with the control group, the micro-CT parameters of BMD, BV/TV, TB. N, and TB. Th were significantly higher. The maximal pull-out force and the bone-to-implant contact value were also higher. Conclusions The local administration of DFO, which is used to activate the HIF-1a signaling pathway, can promote osteogenesis and osseointegration with a prosthesis in osteoporotic bone.


Author(s):  
Afifah Afifah ◽  
Khusnul Muflikhah ◽  
Tri Lestari ◽  
Eman Sutrisna ◽  
Ajeng Kirana ◽  
...  

Background<br />Anemia is a frequent complication of chronic kidney disease (CKD). Anemia in CKD is associated with reduced quality of life, increased cardiovascular disease, cognitive impairment, and mortality. Therefore it is necessary to find an alternative agent for preventing anemia in CKD. Celery is one of the natural substances that have anti-inflammatory, antioxidant, and antihypertensive pharmacological effects. Based on the mechanism of CKD and its progression, celery is thought to prevent anemia in CKD. This research was aimed at evaluating the protective effect of celery extract against anemia in a CKD rat model. <br /><br />Methods<br />This was an experimental laboratory study using 25 male Sprague Dawley rats, aged 2-3 months, they were randomized into 5 groups, namely group A, sham operation; group B, subtotal nephrectomy; group C, D, E, subtotal nephrectomy + 250, 500, 1000 mg/kg BW ethanol extract of celery, respectively. The administration of celery extract was performed 14 days before and 14 days after induction of 5/6 subtotal nephrectomy. The hematological parameters (Hb, RBC, Ht, MCV, MCH, MCHC) and serum creatinine level were measured at the end of the study. Data were analyzed with One Way ANOVA and Kruskal-Wallis test followed by Mann-Whitney test at p&lt;0.05. <br /><br />Results<br />There were no significant differences between groups in Hb, RBC, Ht, MCV (p&gt;0.05) and significant differences between groups in MCH and MCHC (p&lt;0.05). The highest levels of Hb, RBC, and Ht were found in group C.<br /><br />Conclusion<br />Celery ethanol extract at a dose of 250 mg/kg BW/day may prevent anemia in the CKD rat model.


2001 ◽  
Vol 16 (2) ◽  
pp. 75-81 ◽  
Author(s):  
Gracinda De Lourdes Jorge ◽  
Luiz Sergio Leonardi ◽  
Ilka de Fatima Santana Ferreira Boin ◽  
Orlando de Castro e Silva Jr ◽  
Cecilia Amelia Fazzio Escanhoela

The aim of this study was to describe a method for the induction of experimental secondary biliary fibrosis (SBF). Forty-seven Wistar rats were submitted to hepatic duct obstruction (OB group) for thirty days without ligature, section or cannulization causing interruption of biliary flow. This technique was carried out by simple traction of the bile duct passing it through the xiphoid appendix. Nine rats were submitted to a sham operation for bile duct stricture and seven rats comprised the control group. Blood samples were collected for the measurement of total bilirubin (TB), alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Liver fragments were removed for morphological study. Thirty days after surgery TB, AP, ALT and AST levels were significantly increased in the hepatic duct ligation group compared to the sham operated group and the presence of SBF in the OB group was confirmed by morphological study of the liver. There was technical failure in 31.92% cases. The survival was 100% at fifteen days and 82.97% at the end of the experiment. We concluded that this simple surgical technique may be used to study the consequence of bile duct obstruction which could be a reversible process depending on the obstruction time. This technique can be carried out from cholestasis to fibrosis.


2011 ◽  
Vol 89 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Song Zhang ◽  
Ben He ◽  
Steven Goldstein ◽  
Junbo Ge ◽  
Zuyue Wang ◽  
...  

The aims of this study were to explore the changes in expression of myocardial adiponectin (APN), changes in serum APN, and the significance of bisoprolol intervention in acute myocardial infarction (AMI) rats. An AMI rat model was established for the purposes of this study and was used for analysis of serum APN as determined by ELISA. Changes in expression of myocardial APN mRNA and APN protein in AMI rats were determined via reverse transcriptase (RT)–PCR and immunohistochemistry. Serum APN concentration and APN protein expression of the myocardium decreased significantly in the AMI groups compared with the sham operation group, with the lowest serum APN and APN protein expression on day 7 after AMI. On days 7 and 10 after AMI, the expression of myocardial APN mRNA in the AMI groups decreased significantly compared with the sham operation group. However, the APN mRNA increased on day 10 compared with that on day 7. Notably, there was an increase in levels of serum APN and myocardial APN expression after bisoprolol intervention. The expression of myocardial APN and serum APN decreased in AMI rats. APN may be an important protective factor against AMI. Bisoprolol can also protect against AMI because it increases APN expression.


2016 ◽  
Vol 34 (3) ◽  
pp. 184-193 ◽  
Author(s):  
Xiao Xu ◽  
Miao-Miao Wang ◽  
Zhi-ling Sun ◽  
Dan-ping Zhou ◽  
Ling Wang ◽  
...  

Objective To examine the possible impact of moxibustion on the serum proteome of the collagen-induced arthritis (CIA) rat model. Materials and Methods Thirty-six male Sprague-Dawley rats were included in this experiment. The CIA animal model was prepared by injection of type II bovine collagen in Freund's adjuvant on the first and seventh day. The 36 rats were randomly divided into two groups: the untreated CIA group (control), and the CIA plus treatment with moxibustion (CIA+moxi) group. Moxibustion was administered daily at ST36 and BL23 for 7, 14 or 21 days (n=12 rats each). Arthritis score was used to assess the severity of arthritis. At the end of each 7 day treatment, blood samples from the control group and the CIA+moxi group were collected. After removal of high abundance proteins from serum samples, two-dimensional gel combined with matrix-assisted laser desorption ionisation time-of-flight MS/MS (MALDI-TOF-MS/MS) techniques were performed to examine serum protein expression patterns of the CIA rat model with and without moxibustion treatment. In addition, the relevant proteins were further analysed with the use of bioinformatics analysis. Results Moxibustion significantly decreased arthritis severity in the rats in the CIA+moxi group, when compared with the rats in the CIA group 35 days after the first immunisation (p=0.001). Seventeen protein spots which changed >1.33 or <0.77 at p<0.05 using Bonferonni correction for multiple testing were found to be common to all three comparisons, and these proteins were used for classification of functions using the Gene Ontology method. Consequently, with the use of the Ingenuity Pathway Analysis, the top canonical pathways and a predicted proteomic network related to the moxibustion effect of CIA were established. Conclusions Using the proteomics technique, we have identified novel candidate proteins that may be involved in the mechanisms of action underlying the beneficial effects of moxibustion in rats with CIA. Our findings suggest that immune responses and metabolic processes may be involved in mediating the effects of moxibustion. Moreover, periodxiredoxin I (PRDX1) and inositol 1,4,5-triphosphate receptor (IP3R) may be potential targets.


2012 ◽  
Vol 302 (1) ◽  
pp. G145-G152 ◽  
Author(s):  
Vairappan Balasubramaniyan ◽  
Gavin Wright ◽  
Vikram Sharma ◽  
Nathan A. Davies ◽  
Yalda Sharifi ◽  
...  

Ammonia is central in the pathogenesis of hepatic encephalopathy, which is associated with dysfunction of the nitric oxide (NO) signaling pathway. Ornithine phenylacetate (OP) reduces hyperammonemia and brain water in cirrhotic animals. This study aimed to determine whether endothelial NO synthase activity is altered in the brain of cirrhotic animals, whether this is associated with changes in the endogenous inhibitor, asymmetric-dimethylarginine (ADMA) and its regulating enzyme, dimethylarginine-dimethylaminohydrolase (DDAH-1), and whether these abnormalities are restored by ammonia reduction using OP. Sprague-Dawley rats were studied 4-wk after bile duct ligation (BDL) ( n = 16) or sham operation ( n = 8) and treated with placebo or OP (0.6 g/kg). Arterial ammonia, brain water, TNF-α, plasma, and brain ADMA were measured using standard techniques. NOS activity was measured radiometrically, and protein expression for NOS enzymes, ADMA, DDAH-1, 4-hydroxynonenol (4HNE), and NADPH oxidase (NOX)-1 were measured by Western blotting. BDL significantly increased arterial ammonia ( P < 0.0001), brain water ( P < 0.05), and brain TNF-α ( P < 0.01). These were reduced significantly by OP treatment. The estimated eNOS component of constitutive NOS activity was significantly lower ( P < 0.05) in BDL rat, and this was significantly attenuated in OP-treated animals. Brain ADMA levels were significantly higher and brain DDAH-1 significantly lower in BDL compared with sham ( P < 0.01) and restored toward normal following treatment with OP. Brain 4HNE and NOX-1 protein expression were significantly increased in BDL rat brain, which were significantly decreased following OP administration. We show a marked abnormality of NO regulation in cirrhotic rat brains, which can be restored by reduction in ammonia concentration using OP.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H R Helmi ◽  
A P Sunjaya ◽  
D Limanan ◽  
A R Prijanti ◽  
S W A Jusman ◽  
...  

Abstract Background Apelin, an adipokine peptide and its receptor has recently emerged as a key signaling pathway in maintaining cardiac performance at chronic pressure loads. Apelin has been linked to ventricular dysfunction and therefore maybe of pathophysiologic relevance as a candidate biomarker in HF patients. Purpose This study aims to investigate Apelin-13 gene expression and level, and Apelin receptor (APJ) level in a rat model of heart failure induced by chronic systemic hypoxia and their correlation to BNP-45 gene expression and level, the current gold standard biomarker for heart failure, and to cardiac histopathologic changes. The effect of chronic systemic hypoxia on cardiac hypertrophy, remodeling and heart failure parameters is also of interest. Methods Twenty-eight male Sprague-Dawley rats (8–12 weeks of age) were placed in special hypoxic chambers divided into 7 groups – a control group provided with normoxia (atmospheric O2 levels) and 6 exposure groups exposed to hypoxia (8% O2) for 6 hours, 1, 3, 5, 7 and 14 days respectively prior to measurement. Changes in the expression of Apelin and BNP-45 were measured using quantitative real-time PCR, whereas changes in Apelin-13, APJ and BNP-45 levels were measured using ELISA. Histopathology staining using Hematoxylin and Eosin was performed on cardiac tissues post-termination. Results Compared to control, BNP-45 mRNA expression in the hypoxic heart was only significantly different in day 14, whereas, Apelin mRNA expression had showed significantly higher values starting from day 7 onward. This is in line with the evidence of cardiac hypertrophy based on histopathologic examination present from day 7 onwards. BNP-45 and Apelin-13 levels were significantly higher compared to control from day 5 onwards with a peak on day 7. Although significantly higher than control, Apelin-13 and BNP-45 level decreases in day 14 as compared to day 7. Mean APJ levels showed a similar profile with Apelin-13 and BNP-45 levels with a peak in day 7 (4.619 ng/mL). The cardiac Apelin-13 level shows strong significant correlation with BNP-45 levels (r 0.823, p-value 0.0001). There was also a strong significant correlation between APJ receptor levels with Apelin-13 (r 0.9029, p-value 0.001) and BNP-45 (r 0.9062, p-value 0.0009) levels. Apelin-13, APJ and BNP-45 levels also showed strong significant positive correlation to the duration of hypoxia exposure. Conclusion Chronic (≥5 days) and not acute systemic hypoxia in an experimental rat model leads to increase in Apelin-13, APJ and BNP-45 levels. Apelin-13 and BNP-45 were found to significantly increase from 5 days onwards. Apelin mRNA expression was found to show significant increase earlier compared to BNP-45 mRNA expression. Hence, Apelin may serve as a new candidate biomarker for detection of HF due to oxidative stress compared to BNP-45. Exposure to chronic systemic hypoxia can serve as an easily replicable rat model for heart failure. Acknowledgement/Funding Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tarumanagara University, Jakarta, Indonesia


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sang-Yeon Lee ◽  
Jeonghyo Kim ◽  
Sangjin Oh ◽  
Gaon Jung ◽  
Ki-Jae Jeong ◽  
...  

Abstract This study was performed to investigate the Eustachian tube as a potential route for contralateral spreading following intratympanic nanoparticle (NP)-conjugated gentamicin injection in a rat model. Sprague–Dawley rats were divided into three groups and substances were injected in the right ear: group 1 (fluorescent magnetic nanoparticles [F-MNPs], n = 4), group 2 (F-MNP-conjugated gentamicin [F-MNP@GM], n = 2), and control group (no injections, n = 2). T2-weighted sequences corresponding to the regions of interest at 1, 2, and 3 h after intratympanic injection were evaluated, along with immunostaining fluorescence of both side cochlea. The heterogeneous signal intensity of F-MNPs and F-MNP@GM on T2-weighted images, observed in the ipsilateral tympanum, was also detected in the contralateral tympanum in 4 out of 6 rats, recapitulating fluorescent nanoparticles in the contralateral cochlear hair cells. Computational simulations demonstrate the contralateral spreading of particles by gravity force following intratympanic injection in a rat model. The diffusion rate of the contralateral spreading relies on the sizes and surface charges of particles. Collectively, the Eustachian tube could be a route for contralateral spreading following intratympanic injection. Caution should be taken when using the contralateral ear as a control study investigating inner-ear drug delivery through the transtympanic approach.


2017 ◽  
Vol 16 (1) ◽  
pp. 167-167
Author(s):  
M.S. Berke ◽  
Klas S.P. Abelson

Abstract Aims This study investigated the effects of buprenorphine treatment on pain and welfare parameters and model specific parameters in a rat model of monoarthritis to eliminate unnecessary pain from this model. Methods 32 male Sprague Dawley rats were divided into four groups: (1) A negative control without arthritis receiving no analgesia. (2) A positive monoarthritic control group receiving no analgesia, but subcutaneous saline injections twice a day. (3) A positive control with monoarthritis receiving subcutaneous carprofen once a day and saline once a day. (4) A group with monoarthritis receiving subcutaneous buprenorphine twice a day. Monoarthritis was induced with an injection of 0.02 ml Complete Freund’s Adjuvant intra-articularly in the left tibiotarsal joint. Treatment with analgesia was initiated at day 15 and the rats were euthanized at day 23. Results The induced monoarthritis elicited a pronounced acute inflammation. Several parameters such as bodyweight, mobility, stance, joint-stiffness and lameness scores were affected. A marked mechanical hyperalgesia in the tarsal area was observed by Electronic Von Frey testing, but no severe compromise of the animal welfare was seen at any time. Signs of chronic development began to appear from day 10 after the monoarthritic induction. No significant change in serum cytokines and faecal corticosterone measurements was found after administration of buprenorphine. A minor decrease in body weight was seen, and a higher pain tolerance to mechanical stimuli was observed, indicating pain alleviation. The histological examination confirmed monoarthritic development in all monoarthritic rats and revealed periarticular lesions suggesting diffusion of adjuvant from intra-articular injection site to the periphery. Conclusions The study demonstrated that buprenorphine has an analgesic effect in the adjuvant induced monoarthritic rat model, without obvious interference with the development of arthritis.


Sign in / Sign up

Export Citation Format

Share Document