Double Ligature Research Articles

Lipid peroxidation and liver damage in double and simple common bile duct ligation models in male Sprague-Dawley rats

AimsBacterial translocation, defined as the presence of living bacteria or bacterial fragments in both mesenteric lymph nodes or systemic circulation, can cause a severe inflammatory reaction in patients with cirrhosis. This study aimed to compare lipid peroxidation associated with liver damage in different experimental models of bile duct ligation: proximal double ligation and transection versus proximal simple ligation versus sham. Materials and methodsSixty-two male rats underwent one of three bile duct surgical interventions: proximal double ligation and transection (n = 22); proximal simple ligation (n = 19); or sham operation (n = 21). We performed microbiological culture of mesenteric lymph nodes; portal and cava blood, spleen and liver cultures; and histological analysis of liver parenchyma. Samples of blood and liver were obtained at laparotomy for malondialdehyde quantification. Key findingsSerum malondialdehyde levels were significantly higher in simple ligature animals (3.7 nmol/mg, standard deviation [SD] 2.1) compared to controls (1.6 nmol/mg SD 0.5; p = 0.001) or double ligature (0.3 nmol/mg SD 0.3; p = 0.001). Liver malondialdehyde levels were significantly higher in animals subjected to double ligation vs controls (9.0 nmol/mg SD 2.8 vs. 1.7 nmol/mg SD 1.0; p = 0.0007) and simple ligature (2.9 nmol/mg SD 2.0; p = 0.0001). Overall incidence of bacterial translocation was similar in simple and double ligatures (22.2 % and 21 % respectively), and significantly higher than in controls. Significancethe type of bile duct ligation influences the type and localization of lipid peroxidation, but does not influence the development of bacterial translocation.

Viabilidade da castração de cachaços por abordagem pré-escrotal: 30 casos

ABSTRACT: Since the first reports of boar castration, the anesthesia, surgery, and especially the restraint for surgical wound management of large and strong boars may be challenging. Most frequent complications include hemorrhage, excessive edema, infection, abscess, scirrhous cord, inguinal hernia, seroma, hematoma, and death. In order to diminish those complications, we hypothesized that the pre-scrotal approach would be a successful method for orchiectomy in boars and that the complication rate would be low, facilitating post-surgical handling on the commercial swine breeding farms by the owners or handlers. Therefore, the present study aimed to describe our experience performing castration in boars using a pre-scrotal approach on farm-setting. Thirty commercial-breed male boars (weighing 255-410kg) were submitted to dissociative anesthesia protocol and local anesthesia. An 8-10cm skin incision was made cranially to the hemiscrotum, and subcutaneous tissue was bluntly dissected, reaching the tunica dartos, fascia, and vaginal tunica. Mesorchium was bluntly dissected to separate, and a double size-0 transfixion ligature was placed around the spermatic cord that was sharply transected. The procedure was repeated on the contralateral testis using the same skin incision. Short-term complication was restricted to mild scrotal edema in 12 (40%) boars. No wound exudate, surgical site infection or death related to the surgery was recorded. On the long-term follow-up (≥4 months’ post-surgery), all owners stated that the boar was subsequently used as intended (slaughter after the proper boar taint withdrawal time) and their satisfaction with the low degree of difficulty in handling the post-operative care. Herein, the overall complication rate was considered low, the mortality rate was zero, and the pre-scrotal castration approach was successfully performed in all boars. These features confirm the technique as a safe procedure for orchiectomy in boars. Additionally, abolishing the daily dressing of surgical wounds required in open castration techniques, especially when surgical site infection occurs, may provide better welfare for the boars.

Development of an ischemic fracture healing model in mice.

Background and purposeIn fracture healing, ischemia caused by vascular injuries, chronic vascular diseases, and metabolic comorbidities is one of the major risk factors for delayed union and non-union formation. To gain novel insights into the molecular and cellular pathology of ischemic fracture healing, appropriate animal models are needed. Murine models are of particular interest, as they allow to study the molecular aspects of fracture healing due to the availability of both a large number of murine antibodies and gene-targeted animals. Thus, we present the development of an ischemic fracture healing model in mice.Material and methodsAfter inducing a mild ischemia by double ligature of the deep femoral artery in CD-1 mice, the ipsilateral femur was fractured by a 3-point bending device and stabilized by screw osteosynthesis. In control animals, the femur was fractured and stabilized without the induction of ischemia. The femora were analyzed at 2 and 5 weeks after fracture healing by means of radiology, biomechanics, histology, and histomorphometry.ResultsThe surgically induced ischemia delayed and impaired the process of fracture healing. This was indicated by a lower Goldberg score, decreased bending stiffness, and reduced bone callus formation in the ischemic animals when compared with the controls.InterpretationWe introduce a novel ischemic femoral fracture healing model in mice, which is characterized by delayed bone healing. In future, the use of this model may allow both the elucidation of the molecular aspects of ischemic fracture healing and the study of novel treatment strategies.

Hydronephrosis in a Dog Related to Ovariosalpingohysterectomy

Background: Hydronephrosis is the dilation of the pelvis and renal calyxes due to post-renal obstruction. The obstruction is often associated with extraluminal masses, blood clots and ureter ligation in castration procedures. Ureter ligation is reported as a malpractice. The renal function is reestablished if ligation is rapidly undone, but not for obstructions longer than four weeks. Often, clinical signs are results from months to years after the castration, when nephrectomy is the best therapeutic option. This paper aims to report a case of asymptomatic unilateral hydronephrosis in a 10-year-old dog caused by chronic ureter occlusion with Nylon 3.0 suture during an elective procedure.Case: A 10-year-old female pinscher dog, spayed 3 years ago was admitted at the Surgery Department of the Veterinary Hospital of the Federal University of Jataí (HV-UFJ). The animal was taken for periodontal treatment. In the physical and laboratory examination (complete blood count, hepatic and renal biochemical tests) no significant and noteworthy alterations were found. Ultrasonographic examination showed no changes in the topography and echotexture of the left kidney, however the right kidney was not visualized, with an anechoic structure suggestive of advanced and severe hydronephrosis. Therefore, exploratory laparotomy was proposed to identify the observed structure, with the periodontal treatment considered for a later time. So, a retroumbilical incision was made, followed by linea alba and the removal of simple isolated suture remaining from previous surgical procedure. In the cavity, the viscera were isolated and the left kidney was identified, observing preserved anatomy. On the other hand, the right kidney had altered topography and morphology, being exposed after release of adhesions in adjacent structures. The right renal artery and vein were dissected and a double ligature was made. Then, the right ureter was dissected, observing marked dilatation in the proximal portion and the presence of local ligation with Nylon 3.0. Right ureterectomy and right nephrectomy were performed. After nephrectomy, the capsule was ruptured, observing dark fluid in it and absence of tissue compatible with renal parenchyma. The material was preserved in 10% formaldehyde and sent for histopathological examination. Histopathology revealed risk of rupture of the renal capsule due to the advance of renal degeneration and complete absence of parenchyma. However, contrary to the severity of the histopathological, surgical and ultrasonographic findings, the patient did not present clinical signs at the time of diagnosis.Discussion: In the intraoperative evaluation, the cause of the hydronephrosis was verified to be in fact the ligation of the ureter, which may have been accidental or due to the malpractice of the veterinarian surgeon. Other possible causes such as adhesions and granulomas were ruled out because the Nylon 3.0 suture was found in the proximal portion of the right ureter. It is believed that the patient may have presented clinical signs of hydronephrosis that may have been confused by the tutors as postoperative complications, changes that if identified and performed in time, could have avoided the occurrence or worsening of hydronephrosis and subsequent nephrectomy. Clinically, the bitch did not show clinical signs presented in the literature as consistent with hydronephrosis such as polyuria, polydipsia, abdominalgia, external fistula and anorexia. Therefore, it is believed that this case is one of the first reports of the occurrence of severe hydronephrosis without typical clinical manifestations of hydronephrosis. This fact raises a warning about the thorough monitoring in the postoperative period by owners and veterinarians, in addition to highlighting concerns regarding the occurrence of medical malpractice versus surgical accidents. Keywords: castration, malpractice, nephrectomy, nylon.

Securing the base of the appendix during laparoscopic appendectomy.

In contrast to classical appendectomy where the appendiceal stump is secured by a single or double ligature, in laparoscopic appendectomy various ways of securing the stump are mentioned. Each of these methods has advantages and disadvantages. Since different possibilities exist for closing the stump, it is very important to find the optimum method for closure of the appendiceal stump, bearing in mind their simplicity, biocompatibility and price. The aim of this review article has been to present the problem of securing the base of the appendix during laparoscopic appendectomy.

Vaginal Hysterectomy Suturing Skills Training Model and Curriculum.

Declining vaginal hysterectomy numbers in obstetrics and gynecology training programs highlights the need for innovative methods to teach vaginal surgical skills. We describe our experience with a vaginal hysterectomy skills simulation curriculum. A low-fidelity bench model was constructed to simulate four vaginal hysterectomy suturing tasks. A polyvinyl chloride downspout adapter and low-cost materials simulate the Heaney pedicle stitch, simple pedicle stitch, double ligature, and continuous running stitch. Faculty expert vaginal surgeons established proficiency levels for each task. Resident (N=30) pass rates for tasks 1, 2, and 3 were 1 of 30 (3.3%), 7 of 30 (23.3%), and 4 of 30 (13.3%), respectively, for the left side, and 3 of 30 (10%), 9 of 30 (30%), and 10 of 30 (33.3%), respectively, for the right side. For task 4, the pass rate was 14 of 30 (46.7%). The majority of residents felt that the model simulates the technical skills required for vaginal hysterectomy and agreed that vaginal skills laboratory training would improve their ability to perform procedures in the operating room. Ninety-two percent of residents felt that a vaginal surgery skills curriculum would be a useful addition to their simulation education. A proficiency-based vaginal hysterectomy skills simulation curriculum using a low-fidelity model may be an important training and evaluation tool for vaginal surgical skills training.

An unusual case of suicidal double ligature strangulation.

As suicide by ligature strangulation is rare, the correct medico-legal diagnosis may be difficult to establish if there is no clear supporting circumstantial evidence. We report an unusual case of suicide by strangulation with a double ligature. Investigation of the scene of death and pathological findings at autopsy are reported and discussed. We emphasise the importance of an external examination and an on-the-spot investigation.

LEVELS OF NITRIC OXIDE METABOLITES IN RATS WITH HEPATOPULMONARY SYNDROME

<p>Background. System of nitric oxide (NO), which consists of NO, and its metabolites, is very important for<br />various biological processes. NO is signalling molecules and mediators of intracellular and intercellular interaction<br />that causes relaxation of smooth muscles of blood vessel walls, inhibits platelet aggregation and their adherence,<br />is involved in the transmission of nerve impulses, cell proliferation.<br />Objective. The aim of our research was to study the content of nitric oxide metabolites in blood serum and<br />bronchoalveolar lavage, to substantiate their role in pathogenesis of hepatopulmonary syndrome in<br />experiment.<br />Methods. The experiments were performed on 56 outbread male rats, 180-220 g in weight. The first experimental<br />model of hepatopulmonary syndrome (HPS) was made by imposition of double ligature on common<br />bile duct and its further dissection with a scalpel. The second experimental HPS model was made by 8-week intragastric<br />administration of oil solution CCl4 (400 g per 1 L), 0.5 ml per 100 g of body weight on the first day of<br />the experiment, 0.3 ml per 100 g on the third day of the experiment and then every third day until the end of the<br />experiment 0.3 ml per 100 g. A mixture of corn flour, lard and cholesterol and alcohol solution was added to the<br />standard diet of the rats.<br />Results. The total content of nitric oxide metabolites in blood serum of the rats of the experimental group<br />No.1 (on the 31st day after the common bile duct ligation) was significantly increased in 3.9 times (p1<0,001) if<br />compared with the control group №1. In the rats of the 2nd experimental group (with carbon tetrachloride induced<br />cirrhosis) the total content of nitric oxide metabolites in blood serum also significantly increased in 3.1 times<br />(p1<0,001). Comparison of nitric oxide metabolites content in blood serum and bronchoalveolar lavage, which<br />directly indicated about the processes in lung tissue, was great importance.<br />Conclusions. So, in rats with experimental hepatopulmonary syndrome activation of nitroxydergic process<br />by significant increase in nitric oxide metabolites in blood serum and bronchoalveolar lavage took place.<br />KEYWORDS: hepatopulmonary syndrome, nitric oxide metabolites.</p>

Evaluation of the results from surgical treatment of fractures of the lateral extremity of the clavicle, using the double ligature technique

ObjectiveTo evaluate the incidence of consolidation in surgical treatment of fractures of the lateral extremity of the clavicle using the double subcoracoid ligature technique, with nonabsorbable No. 5 thread. MethodsBetween May 1993 and June 2013, the Shoulder and Elbow Group of our service surgically treated 116 patients (116 shoulders) with fractures of the lateral extremity of the clavicle. Among these, we were able to reassess 65 cases. The surgical technique used consisted of double subcoracoid ligature with two nonabsorbable threads. In two patients classified as type III, we had to combine this technique with use of an interfragmentary screw for fixation of the intra-articular portion of the acromioclavicular joint. ResultsWe achieved fracture consolidation in 90%. Fourteen cases (21%) evolved with major complications: four cases of pseudarthrosis, five of adhesive capsulitis, two of delayed consolidation and three of loss of reduction. Two cases (3%) evolved with minor complications of skin granuloma. ConclusionThe double ligature technique for fractures of the lateral extremity of the clavicle promotes the stabilization needed for consolidation to take place, without the need for synthesis using metal components. It avoids reoperation for the synthesis material to be removed. Moreover, it is a low-cost procedure with good reproducibility and preservation of the acromioclavicular joint.

Avaliação dos resultados do tratamento cirúrgico das fraturas da extremidade lateral da clavícula pela técnica do amarrilho duplo

Objectiveto evaluate the incidence of consolidation in surgical treatment of fractures of the lateral extremity of the clavicle using the double subcoracoid ligature technique, with nonabsorbable No. 5 thread. Methodsbetween May 1993 and June 2013, the Shoulder and Elbow Group of our service surgically treated 116 patients (116 shoulders) with fractures of the lateral extremity of the clavicle. Among these, we were able to reassess 65 cases. The surgical technique used consisted of double subcoracoid ligature with two nonabsorbable threads. In two patients classified as type III, we had to combine this technique with use of an interfragmentary screw for fixation of the intra‐articular portion of the acromioclavicular joint. Resultswe achieved fracture consolidation in 90%. Fourteen cases (21%) evolved with major complications: four cases of pseudarthrosis, five of adhesive capsulitis, two of delayed consolidation and three of loss of reduction. Two cases (3%) evolved with minor complications of skin granuloma. Conclusionthe double ligature technique for fractures of the lateral extremity of the clavicle promotes the stabilization needed for consolidation to take place, without the need for synthesis using metal components. It avoids reoperation for the synthesis material to be removed. Moreover, it is a low‐cost procedure with good reproducibility and preservation of the acromioclavicular joint.

Suicidal strangulation by double ligature: A case report

This article reports a self-strangulation suicide in which a double complex group of ligatures was used. Although similar cases have been referenced in forensic literature, this case is notable because of the unusual method used by the victim. A 61-year-old man was found in a locked room with a double elaborate ligature comprising six wire clothes hangers completely encircling the neck and a black rubber band in a double loop. Autopsy also documented parallel superficial cut lesions in proximal forearm interpreted as hesitation marks. It stresses the importance of characteristics such as analysis of number of ligatures, position of the knots, number of knots and turns of ligature marks and the absence of any defense and relevant internal injuries inherent to suicide ligature strangulation cases.

Permanent Cerebral Vessel Occlusion <em>via</em> Double Ligature and Transection

Stroke is a leading cause of death, disability, and socioeconomic loss worldwide. The majority of all strokes result from an interruption in blood flow (ischemia). Middle cerebral artery (MCA) delivers a great majority of blood to the lateral surface of the cortex, is the most common site of human stroke, and ischemia within its territory can result in extensive dysfunction or death. Survivors of ischemic stroke often suffer loss or disruption of motor capabilities, sensory deficits, and infarct. In an effort to capture these key characteristics of stroke, and thereby develop effective treatment, a great deal of emphasis is placed upon animal models of ischemia in MCA. Here we present a method of permanently occluding a cortical surface blood vessel. We will present this method using an example of a relevant vessel occlusion that models the most common type, location, and outcome of human stroke, permanent middle cerebral artery occlusion (pMCAO). In this model, we surgically expose MCA in the adult rat and subsequently occlude via double ligature and transection of the vessel. This pMCAO blocks the proximal cortical branch of MCA, causing ischemia in all of MCA cortical territory, a large portion of the cortex. This method of occlusion can also be used to occlude more distal portions of cortical vessels in order to achieve more focal ischemia targeting a smaller region of cortex. The primary disadvantages of pMCAO are that the surgical procedure is somewhat invasive as a small craniotomy is required to access MCA, though this results in minimal tissue damage. The primary advantages of this model, however, are: the site of occlusion is well defined, the degree of blood flow reduction is consistent, functional and neurological impairment occurs rapidly, infarct size is consistent, and the high rate of survival allows for long-term chronic assessment.

Translumenal Esophageal Anastomosis for Natural Orifice Translumenal Endoscopic Surgery: An Ex Vivo Feasibility Study

This study aimed to develop a novel procedure for esophagoesophageal anastomosis for natural orifice translumenal endoscopic surgery (NOTES). An ex vivo feasibility study was performed in eight porcine models. The procedure was as follows: (1) A BraceBar™ (Olympus Medical Systems Corp., Tokyo, Japan), a double T-bar suturing device, was placed endoscopically at the blind end of the upper esophagus (UE). (2) The blind end was incised, and the scope was advanced out of the esophagus. (3) A balloon catheter was inserted into the lower esophagus (LE). (4) The catheter and a thread on the BraceBar were withdrawn so that the end of the UE was inverted, and the LE was pulled into the UE. (5) After the catheter was removed, a short tube was placed inside the duplicated part of the esophagus via the transgastric route. (6) A double ligature was performed using a ligating device over the tube. A liquid leak test was performed after the procedure. All steps in this procedure were technically successful under the endoscopic visualization without any assistance from outside of the esophagus. The median time of this procedure was 31 (23-66) minutes. The median internal pressure of the UE was 122 (82-142) mm Hg when the anastomosed esophagus was separated into two specimens during the leak test. Translumenal esophagoesophageal anastomosis was feasible. The duration of the procedure was short, and the anastomoses appear to have sufficient strength for use in clinical practice. An in vivo survival study is needed to confirm the safety and reliability of this NOTES procedure.

Manipulating Arterial Fluid-shear Stress and Arteriogenesis in the Brain

Occlusions of the brain arteries remain life-threatening diseases and are associated with devastating morbidity. The basic, physiological and spontaneous reactions of the organism to vascular occlusion are to develop adaptative collateral circulation(s) outside the ischemic region, which can potentially replace the feeding capacity of the larger arteries. From the point of view of the interventionalist, the intracranial anatomy, as well as the extreme mechanosensitivity of the brain arteries, leave few degrees of freedom to surgical actions, in contrast to situations elsewhere in the body. Moreover there are major differences between the brain arteries and their constitutive vascular cells of the brain with arteries lying outside the brain. The cerebral vasculature is made of low-resistance vessels containing neural crest-derived vascular cells opposing high-resistance vessels made of mesoderm-derived vascular smooth muscle cells in the peripheral arteries. The paper by Wilma Schierling and colleagues is one example of the recent attempts to develop new therapeutic options aimed at favoring the brain arteriogenesis by acting upon the haemodynamic properties of cerebral arteries by modifying one of the blood flow components, i.e. the fluid-shear stress which previously has been shown to be the pivotal trigger of cerebral arteriogenesis. Various experimental models have been used. The present experimental model is based upon double ligature,

Sperm Migration in Pigs after Deep Intrauterine and Intraperitoneal Insemination

Deep intrauterine insemination in pigs allows sperm deposition only into one uterine horn, but bilateral fertilization of oocytes occurs. How the sperm reach the contralateral oviduct remains disputable. The aim of this experiment was to study possible transperitoneal and/or transuterine sperm migration ways. Follicle growth and ovulation were induced in 24 peripubertal gilts with eCG and hCG 72 h after eCG. Endoscopic intrauterine insemination (IUI) was performed 32 h after hCG with 20 ml of extended semen (60 × 10(6) spermatozoa) as follows: Group CONTROL (n=8) received IUI into the right horn, and the left horn served as non-treated control; Group LIGATURE (n=8) received IUI into the right horn, and the left horn was closed by endoscopic double ligature close to the bifurcation; Group INTRAPERITONEAL (IPI; n=8) received IUI into the right uterine horn, the left horn was closed by double ligature and semen was deposited intraperitoneally at the surface of the left ovary. Genital tracts were removed 65-66 h after hCG, the oviducts were flushed and ova (n=299) were analyzed for fertilization and cleavage. Furthermore, the accessory spermatozoa count/oocyte was graded as 0, without spermatozoa, 1, <5 spermatozoa, 2, 5-50 spermatozoa, 3, 50-100 spermatozoa and 4, >100 spermatozoa. The results indicate that low dose IUI into one horn provides a lower grade of accessory spermatozoa in the contra-lateral side (1.6 vs. 2.8). No spermatozoa were found in ova flushed from oviducts of the ligated uterine horn, even after intraperitoneal insemination (P<0.05), and no fertilization occurred, respectively. Our results clearly indicate that after low dose IUI into one uterine horn, spermatozoa reach the contralateral oviduct via transuterine migration.

The First Closure of the Persistent Ductus Arteriosus

Congenital heart disease began to be a treatable condition when, in 1938, Robert Edward Gross first successfully ligated a persistent ductus arteriosus. This overview traces the historical development from Munro's first idea of how to close a patent ductus, presented in 1907, to the clinical ligation or division of the ductus. Surgical treatment of the infected ductus began with an unsuccessful attempt by Strieder, but it was not until Tubbs' and Touroff's successful operations that it was actually accomplished.

Melatonin prevents brain oxidative stress induced by obstructive jaundice in rats

The aim of the study was to analyze the impact of melatonin on brain oxidative stress in experimental biliary obstruction. Cholestasis was done by a double ligature and section of the extrahepatic biliary duct. Melatonin was injected intraperitoneally (500 microg/kg/day). Malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) contents were determined in the brain tissue. Biliary obstruction raised MDA and reduced GSH contents in the cortex, cerebellum, and hypothalamus areas. Moreover, the scavenger enzyme activity significantly dropped in all areas of the brain. Melatonin drastically reduced MDA concentration and enhanced GSH concentration, as well as all antioxidant enzyme activity in all brain areas obtained from the bile duct-ligated animals. In conclusion, the treatment with melatonin decreased lipid peroxidation and recovered the antioxidant status in the brain from cholestatic animals.

Effect of glialin on cardiac ventricular arrhythmias and myocardial conduction system in dogs

Intravenous glialin in a dose of 7 mg/kg suppressed the number of ectopic contractions caused by double ligature of the left coronary artery by the method of Harris and almost 2-fold prolonged animal life-span in comparison with the control. The maximum antiarrhythmic effect of glialin developed after 180 min and persisted for 5 h. Glialin injected intravenously (10 mg/kg) after myocardial infarction under conditions of programmed electrical stimulation inhibited conduction of evoked impulse in the atria, Purkinje fibers, and ventricular myocardium and did not modify the effective refractory periods of the atria and ventricles.

Establishment of Animal Models for Three Types of Pancreatitis and Analyses of Regeneration Mechanisms

To investigate the mechanisms underlying the onset and progress of pancreatitis, 3 animal models (chronic, acute, and severe pancreatitis) were established by double ligature of the pancreatic duct, injection with cerulein, or injection with cerulein + double ligature of the pancreatic duct. We prepared a control and 3 experimental groups: group 1 (untreated control), group 2 (a chronic pancreatitis model; the pancreatic tail was exposed through a midline incision, and the pancreatic duct from this part was double-ligated), group 3 (an acute pancreatitis model; cerulein was intraperitoneally injected 7 times on day 0), and group 4 (a severe pancreatitis model; the double ligature of the pancreatic duct plus injection of cerulein). Kinetic observations of survival rate, relative pancreatic weight, and the macroscopical and microscopical diagnoses and observations of the changes in endocrine function clearly show that these 3 murine models of pancreatitis can serve as human models for chronic, acute, and severe pancreatitis. Furthermore, pancreas duodenum homeobox 1, cytokeratin 19, and Ki67 are expressed at the site of injury in the pancreas, resulting from the injection with cerulein and/or double ligature of the pancreatic ducts and indicating that there remains a tissue-regenerative capacity. These 3 mouse models could serve as human models for chronic, acute, and severe pancreatitis. Furthermore, cells of the epithelial lineage might participate in tissue regeneration in chronic, acute, and severe pancreatitis.

Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment

Cholestasis, or impaired bile flow, occurs in a wide variety of liver diseases and causes hepatic damage by retention and accumulation of toxic hydrophobic bile salts inducing persistent inflammation and oxidative stress. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and anti-inflammatory agent against autoimmune disease, on hepatic damage produced by double ligature of the extrahepatic biliary duct in Wistar Albino rats. Cholestasis was done by double ligature and section of the extrahepatic biliary duct (BDL). Leflunomide was given i.g. 10 mg/kg/day. The severity of cholestasis and hepatic injury was determined by changes in the plasma enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and levels of direct bilirubin. Malondialdehyde (MDA), protein carbonyl (PC), nitric oxide (NO), catalase (CAT) and superoxide dismutase (SOD) were determined to the oxidative status in the liver tissue. Myeloperoxidase (MPO) activity and levels of tissue hydroxyproline (HPR) were determined to neutrophil activation and collagen accumulation, respectively. Further, histological changes were studied. Treatment with leflunomide markedly reduced serum transaminase activities as compared to BDL rats. At the same time leflunomide significantly inhibited increases in liver MDA, PC and NO levels and also attenuated the depletion of CAT and SOD in the liver after bile duct ligation. Similarly, increase in tissue MPO activity and HPR due to BDL was also attenuated by leflunomide treatment. These findings were supported by histopathological findings. These findings suggested that leflunomide can attenuate hepatic damage in extrahepatic cholestasis by prevention of oxidative stress and inflammatory process.