Complete Ligation Research Articles

Surgical treatment and outcome of intrahepatic shunts in 12 cats.

The objective of this case series was to describe the presentation, surgical treatment and outcome of a congenital intrahepatic portosystemic shunt (IHPSS) in 12 cats. A retrospective case series of cats undergoing surgical treatment for an IHPSS was undertaken. Signalment, clinical signs, imaging, surgical treatment, complications and short-term outcome (<30 days) were obtained using medical records. Long-term outcome (>1 year after first surgery) was obtained, where possible, using a health-related quality of life owner questionnaire. Seven cats were diagnosed with a left divisional shunt, three with a central divisional shunt and two with a right divisional shunt using intraoperative mesenteric portovenography. Three cats tolerated complete acute suture attenuation, eight cats underwent partial suture attenuation, four of which received complete suture ligation at a second surgery, and one cat underwent partial attenuation with a thin film band. Six cats (50%) developed post-attenuation neurological signs (PANS) after first surgery and two cats (17%) died or were euthanased due to severe PANS. Long-term outcome was available for eight cats (67%), with a median follow-up time of 1743 days (range 364-2228), and was described as excellent in five cats (63%), fair in two cats (25%) and poor in one cat (12%). Few papers exist that describe the presentation, intraoperative imaging, treatment and outcome of IHPSSs in cats. This is the first to describe surgical attenuation with a thin film band in a cat with an IHPSS. This case series reports excellent long-term outcomes in a majority of surgically treated cats with IHPSS.

Neutrophils Mediate Pulmonary Artery Thrombosis In Situ.

Pulmonary embolism is a life-threatening condition, which can result in respiratory insufficiency and death. Blood clots occluding branches of the pulmonary artery (PA) are traditionally considered to originate from thrombi in deep veins (usually in legs). However, growing evidence suggests that occlusion of the vessels in the lungs can develop without preceding deep vein thrombosis (DVT). In this work, we used an inferior vena cava (IVC) complete ligation model of DVT in Wistar rats to explore the possibility and mechanisms of PA thrombosis under the conditions where all routes of thrombotic mass migration from peripheral veins are blocked. We demonstrate that rats both with normal and reduced neutrophil counts developed thrombi in the IVC, although, neutropenia caused a substantial decrease in thrombus size and a shift from fresh fibrin toward mature fibrin and connective tissue inside the thrombus. Massive fibrin deposition was found in the PA branches in the majority of DVT rats with normal neutrophil counts, but in none of the neutropenic animals. Neutrophil ablation also abolished macroscopic signs of lung damage. Altogether, the results demonstrate that thrombi in the lung vasculature can form in situ by mechanisms that require local neutrophil recruitment taking place in the DVT setting.

Quantitative analysis of contrast-enhanced ultrasound estimates intrahepatic portal vascularity in dogs with single extrahepatic portosystemic shunt.

To evaluate the clinical impact on quantitative analysis of contrast-enhanced ultrasound (CEUS) on single extrahepatic portosystemic shunt (PSS) in dogs. 21 client-owned dogs with single extrahepatic PSS and 5 healthy Beagles. In all dogs, CEUS was performed to calculate the rising time (RT), rising rate (RR), and portal vein-to-hepatic parenchyma transit time (ΔHP-PV) from the time-intensity curve obtained in the hepatic parenchyma and portal vein. All dogs in the PSS group underwent preoperative CT angiography (CTA) and surgery. The CEUS variables in the PSS group were compared with those in the healthy dogs (control group) and were analyzed for shunt types and grades of intrahepatic portal venous branches based on CTA findings, intraoperative portal pressure, and surgical procedures. All 3 CEUS variables showed no significant differences between the PSS and control groups. The RT and ΔHP-PV in the left gastrophrenic shunt group were significantly longer than in the other shunt types. In the intrahepatic portal vascularity, the RT in grade 1 was significantly shorter than in grades 3 and 4, and the RR in grade 1 was significantly higher than in grade 4. The RT and ΔHP-PV were significantly correlated with portal pressure variables. The RT in dogs with partial ligation was significantly shorter than in dogs with complete ligation and percutaneous transvenous coil embolization. Quantitative assessments of CEUS may be useful for estimating intrahepatic portal vascularity in dogs with single extrahepatic PSS.

Extended Lymphadenectomy for Proximal Transverse Colon Cancer: Is There a Place for Standardization?

Background and Objectives: Complete mesocolon excision and high vascular ligation have become a standard procedure in the treatment of colon cancer. The transverse colon has certain embryological and anatomical particularities which require special attention in case of oncological surgeries. Proximal transverse colon cancer (TCC) can metastasize to the lymph nodes in the gastrocolic ligament. The aim of this study is to assess the tumor involvement of these lymph nodes and to determine the applicability of gastrocolic ligament lymph nodes dissection as the standard approach for proximal transverse colon cancer. Materials and Methods: this study analyzes the cases of patients admitted to the Surgery Department, diagnosed with proximal transverse colon cancer, with tumor invasion ≥ T2 and for which complete mesocolon excision with high vascular ligation and lymphadenectomy of the gastrocolic ligament (No. 204, 206, 214v) were performed. Results: A total of 43 cases operated during 2015–2020 were included in the study. The median total number of retrieved central lymph nodes was 23 (range, 12–38), that had tumor involvement in 22 cases (51.2%). Gastrocolic ligament tumor involvement was found in 5 cases (11.6%). The median operation time was 180 min, while the median blood loss was 115 mL (range 0–210). The median time of hospitalization was 6 days (range, 5–11). Grade IIIA in the Clavien-Dindo classification was noticed in 3 patients, with no mortality. Upon Kaplan–Meier analysis, tumors > T3 (p < 0.016) and lymph node ratio < 0.05 (p < 0.025) were statistically significant. Conclusions: lymph node dissection of the gastrocolic ligament in patients with advanced proximal transverse colon cancer may improve the oncological outcome in T3/T4 tumors, and therefore standardization could be feasible

Left Atrial Appendage Closure: Novel Cor-Knot Lasso Technique Ensures Complete and Safe Ligation

The significance of the left atrial appendage has been well known for a half century. Surgeons used a number of left atrial appendage closure techniques to reduce the risk of stroke without increasing the chance of bleeding from fragile left atrial appendage. Removal and oversewing are simple and effective. Current procedures, however, have the disadvantage of 30% to 40% residual appendage. Here, we discuss our innovative lasso technique using a Cor-Knot device for left atrial appendage closure in 50 consecutive patients between January 2018 and January 2019 who underwent mitral valve surgery. This technique ensured complete closure, with no new cerebrovascular events during the 2-year follow-up.

Andrographolide Promotes Interaction Between Endothelin-Dependent EDNRA/EDNRB and Myocardin-SRF to Regulate Pathological Vascular Remodeling.

IntroductionPathological vascular remodeling is a hallmark of various vascular diseases. Smooth muscle cell (SMC) phenotypic switching plays a pivotal role during pathological vascular remodeling. The mechanism of how to regulate SMC phenotypic switching still needs to be defined. This study aims to investigate the effect of Andrographolide, a key principle isolated from Andrographis paniculate, on pathological vascular remodeling and its underlying mechanism.MethodsA C57/BL6 mouse left carotid artery complete ligation model and rat SMCs were used to determine whether Andrographolide is critical in regulating SMC phenotypic switching. Quantitative real-time PCR, a CCK8 cell proliferation assay, BRDU incorporation assay, Boyden chamber migration assay, and spheroid sprouting assay were performed to evaluate whether Andrographolide suppresses SMC proliferation and migration. Immunohistochemistry staining, immunofluorescence staining, and protein co-immunoprecipitation were used to observe the interaction between EDNRA, EDNRB, and Myocardin-SRF.ResultsAndrographolide inhibits neointimal hyperplasia in the left carotid artery complete ligation model. Andrographolide regulates SMC phenotypic switching characterized by suppressing proliferation and migration. Andrographolide activates the endothelin signaling pathway exhibited by dramatically inducing EDNRA and EDNRB expression. The interaction between EDNRA/EDNRB and Myocardin-SRF resulted in promoting SMC differentiation marker gene expression.ConclusionAndrographolide plays a critical role in regulating pathological vascular remodeling.

Expanding the versatility and scope of the oxime ligation: rapid bioconjugation to disulfide-rich peptides.

The oxime ligation is a valuable bioorthogonal conjugation reaction but with limited compatibility with disulfide-rich peptides/proteins and time-sensitive applications. Here we overcome these limitations by introducing a strategy that supports regiospecific control, oxidative folding, production of stable aminooxy-precursors for on-demand modification, and complete ligation within 5 min.

Functional and Molecular Characterisation of Heart Failure Progression in Mice and the Role of Myosin Regulatory Light Chains in the Recovery of Cardiac Muscle Function

Heart failure (HF) as a result of myocardial infarction (MI) is a major cause of fatality worldwide. However, the cause of cardiac dysfunction succeeding MI has not been elucidated at a sarcomeric level. Thus, studying the alterations within the sarcomere is necessary to gain insights on the fundamental mechansims leading to HF and potentially uncover appropriate therapeutic targets. Since existing research portrays regulatory light chains (RLC) to be mediators of cardiac muscle contraction in both human and animal models, its role was further explored In this study, a detailed characterisation of the physiological changes (i.e., isometric force, calcium sensitivity and sarcomeric protein phosphorylation) was assessed in an MI mouse model, between 2D (2 days) and 28D post-MI, and the changes were related to the phosphorylation status of RLCs. MI mouse models were created via complete ligation of left anterior descending (LAD) coronary artery. Left ventricular (LV) papillary muscles were isolated and permeabilised for isometric force and Ca2+ sensitivity measurement, while the LV myocardium was used to assay sarcomeric proteins’ (RLC, troponin I (TnI) and myosin binding protein-C (MyBP-C)) phosphorylation levels and enzyme (myosin light chain kinase (MLCK), zipper interacting protein kinase (ZIPK) and myosin phosphatase target subunit 2 (MYPT2)) expression levels. Finally, the potential for improving the contractility of diseased cardiac papillary fibres via the enhancement of RLC phosphorylation levels was investigated by employing RLC exchange methods, in vitro. RLC phosphorylation and isometric force potentiation were enhanced in the compensatory phase and decreased in the decompensatory phase of HF failure progression, respectively. There was no significant time-lag between the changes in RLC phosphorylation and isometric force during HF progression, suggesting that changes in RLC phosphorylation immediately affect force generation. Additionally, the in vitro increase in RLC phosphorylation levels in 14D post-MI muscle segments (decompensatory stage) enhanced its force of isometric contraction, substantiating its potential in HF treatment. Longitudinal observation unveils potential mechanisms involving MyBP-C and key enzymes regulating RLC phosphorylation, such as MLCK and MYPT2 (subunit of MLCP), during HF progression. This study primarily demonstrates that RLC phosphorylation is a key sarcomeric protein modification modulating cardiac function. This substantiates the possibility of using RLCs and their associated enzymes to treat HF.

Fascial space priority approach for laparoscopic complete mesocolic excision (CME) plus central vascular ligation or extended lymphadenectomy (CVL/D3) in right-sided colon cancer (with video).

Fascial space priority approach for laparoscopic complete mesocolic excision (CME) plus central vascular ligation or extended lymphadenectomy (CVL/D3) in right-sided colon cancer (with video).

USP10 exacerbates neointima formation by stabilizing Skp2 protein in vascular smooth muscle cells

The underlying mechanism of neointima formation remains unclear. Ubiquitin-specific peptidase 10 (USP10) is a deubiquitinase that plays a major role in cancer development and progression. However, the function of USP10 in arterial restenosis is unknown. Herein, USP10 expression was detected in mouse arteries and increased after carotid ligation. The inhibition of USP10 exhibited thinner neointima in the model of mouse carotid ligation. In vitro data showed that USP10 deficiency reduced proliferation and migration of rat thoracic aorta smooth muscle cells (A7r5) and human aortic smooth muscle cells (HASMCs). Mechanically, USP10 can bind to Skp2 and stabilize its protein level by removing polyubiquitin on Skp2 in the cytoplasm. The overexpression of Skp2 abrogated cell cycle arrest induced by USP10 inhibition. Overall, the current study demonstrated that USP10 is involved in vascular remodeling by directly promoting VSMC proliferation and migration via stabilization of Skp2 protein expression.

Paeonol Suppresses Vasculogenesis Through Regulating Vascular Smooth Muscle Phenotypic Switching

Objective: Smooth muscle cell (SMC) phenotypic switching is associated with development of a variety of occlusive vascular diseases. Paeonol has been reported to be involved in suppressing SMC proliferation. However, it is still unknown whether paeonol can regulate SMC phenotypic switching, and which eventually result in suppressing vasculogenesis. Methods: Murine left common carotid artery was injured by completely ligation, and paeonol was administrated by intraperitoneal injection. Hematoxylin and eosin (H&E) staining was performed to visualize vascular neointima formation. Rat aortic SMCs were used to determine whether paeonol suppresses cell proliferation and migration. And murine hind limb ischemia model was performed to confirm the function role of paeonol in suppressing vasculogenesis. Results: Complete ligation of murine common carotid artery successfully induced neointima formation. Paeonol treatment dramatically reduced the size of injury-induced neointima. Using rat aortic primary SMC, we identified that paeonol strongly suppressed cell proliferation, migration, and decreased extracellular matrix deposition. And paeonol treatment dramatically suppressed vasculogenesis after hind limb ischemia injury. Conclusion: Paeonol could regulate SMC phenotypic switching through inhibiting proliferation and migration of SMC, which results in inhibiting ischemia-induced vasculogenesis.

Cholangioscopy and double-balloon enteroscopy mediated "sandwich puncture" of a completely closed choledochojejunostomy.

Video 1Percutaneous cholangioscopy was performed to confirm complete closure of the choledochojejunostomy. Percutaneous cholangioscopy revealed complete closure of the anastomosis. Our attempt to pass a guidewire through the anastomosis failed accordingly.

Postcholecystectomy biliary injuries: frequency, and role of early versus late endoscopic retrograde cholangiopancreatography.

Bile duct injuries are not infrequently seen during hepatobiliary surgery, particularly after liver transplantation and cholecystectomy. The current study aims to figure out the frequency of postcholecystectomy biliary injuries (PCBI) and the role of early versus late endoscopic retrograde cholangiopancreatography (ERCP) in their management. Totally 960 cases operated by both laparoscopic and open cholecystectomy were evaluated in the current study. In total, 942 cases were operated in our institutes, by both laparoscopic (n = 925) and open (n = 17) cholecystectomy, and the frequency of PCBI among patients operated in our institutes was (9/942) 0.95%. Additional 18 cases of PCBI referred to our centers were included in the study. One patient was treated by repair during the surgery, in the remaining 26 patients, ERCP management was attempted. The full details of the 26 patients regarding ERCP management were discussed. The overall success rate of ERCP management was 88.46% (23/26), whereas 11.54% of cases were treated surgically by choledochal-jejunal anastomosis due to complete common bile duct ligation. There were no differences between patients treated by early (first week) versus late (after the first week) ERCP regarding the needed interventions, type of PCBI, type and diameter of the inserted stents, and the overall success. There were no adverse events associated with ERCP management. ERCP was valuable in the treatment of 88.46% of injured cases. There were no differences between early and late ERCP in the treatment of PCBI. Furthermore, ERCP management was not associated with adverse events.

Plasminogen activator inhibitor 1 and venous thrombosis in pancreatic cancer

AbstractPancreatic cancer patients have a high risk of venous thromboembolism (VTE). Plasminogen activator inhibitor 1 (PAI-1) inhibits plasminogen activators and increases the risk of thrombosis. PAI-1 is expressed by pancreatic tumors and human pancreatic cell lines. However, to date, there are no studies analyzing the association of active PAI-1 and VTE in pancreatic cancer patients. We investigated the association of active PAI-1 in plasma and VTE in pancreatic cancer patients. In addition, we determined if the presence of human pancreatic tumors expressing PAI-1 impairs venous thrombus resolution in mice. Plasma levels of active PAI-1 in patients with pancreatic cancer and mice bearing human tumors were determined by enzyme-linked immunosorbent assay. We measured PAI-1 expression in 5 different human pancreatic cancer cell lines and found that PANC-1 cells expressed the highest level. PANC-1 tumors were grown in nude mice. Venous thrombosis was induced by complete ligation of the inferior vena cava (IVC). Levels of active PAI-1 were independently associated with increased risk of VTE in patients with pancreatic cancer (subdistribution hazard ratio per doubling of levels: 1.39 [95% confidence interval, 1.09-1.78], P = .007). Mice bearing PANC-1 tumors had increased levels of both active human and active mouse PAI-1 and decreased levels of plasmin activity. Importantly, mice bearing PANC-1 tumors exhibited impaired venous thrombus resolution 8 days after IVC stasis compared with nontumor controls. Our results suggest that PAI-1 contributes to VTE in pancreatic cancer.

Application and outcomes of a standardized lymphadenectomy in laparoscopic right hemicolectomy requiring ligation of the middle colic artery.

Complete mesocolic excision with central vessel ligation may be important for accurate staging and improving the prognosis of right-sided colon cancer. Although the procedure is often performed laparoscopically, approaching the middle colic artery (MCA) is technically demanding, especially when complete ligation of arteries at their roots is desired. We standardized our laparoscopic approach by establishing the dissection boundary along the superior mesenteric artery to achieve D3 lymphadenectomy in the region of the MCA. The aim of the present study was to evaluate, on the basis of perioperative and short-term oncologic outcomes, the feasibility and safety of our technique METHODS: We conducted a retrospective study on consecutive patients with cancer located at the ascending colon and transverse colon who had laparoscopic right hemicolectomy requiring ligation of the MCA. There were 41 patients (22 males, median age 71years [range 49-86] years). The median operation time was 285min, and blood loss volume was 40mL. Conversion to open surgery was required in 1 case. Complications that were Clavien-Dindo grade III or above occurred in 3 patients (7.3%). There was no anastomotic leakage. The median number of lymph nodes harvested was 46. Our technique was shown to be a safe, feasible, and useful strategy for performance of right hemicolectomy requiring ligation of the MCA in cases of colon cancer. The technique facilitates maximal lymph node dissection. Having obtained favorable outcomes, we look forward to investigation into long-term outcomes.

Quadruplex-Templated and Catalyzed Ligation of Nucleic Acids.

Template-guided chemical reactions between nucleic acid strands are an important process in biomedical research. However, almost all of these reactions employ an oligonucleotide-templated approach that is based on the double-helix alignment. The moderate stability of the double helix makes this approach unsuitable for many chemical reactions, so alternative nucleic acid alignment mechanisms, demonstrating higher thermal and chemical stability, are desirable. Earlier, we described a noncovalent coupling mechanism between DNA strands through a quadruplex-and-Mg2+ connection (QMC). QMC is based on G-quadruplexes and allows unusually stable and specific interactions. Herein, a novel catalytic nucleic acid reaction, based on QMC, is described. This approach uses G-tetrads as a structural and recognition element without employing Watson-Crick complementarity rules at any stage of substrate/catalyst formation or interaction between them. Quadruplex-templated ligation can be achieved through the self-ligation of two nucleic acid strands, or through a quadruplex catalyst, which forms a G-triplex and specifically connects the strands. The process is extraordinarily robust and efficient. For instance, the ligation of carbodiimide-activated substrates can proceed in boiling solutions, and complete ligation is demonstrated within a minute. The quadruplex-templated and catalyzed reactions will create new opportunities for chemical reactions requiring harsh experimental conditions.

The Surgical Approach to Hysterectomy in a Patient with Mullerian Duct Anomaly

Study Objective To present the key surgical steps to complete hysterectomy safely in the presence of uterine anomalies. Design An educational video reviewing Mullerian duct anomalies, their associated anatomic malformations, and the steps to safely complete laparoscopic hysterectomy in a patient with these anomalies. Setting Minimally Invasive Gynecology division at a tertiary care hospital. Patients or Participants N/A Interventions A 45-year-old female undergoing robotic-assisted laparoscopic hysterectomy with presence of Mullerian duct anomaly including proximal vaginal septum with two cervices. Surgical intervention including the robotic localization and resection the proximal vaginal septum. Key points of surgical safety are reviewed including complete bilateral ureterolysis and ligation of the uterine arteries at their origin. Measurements and Main Results N/A Conclusion Minimally invasive approaches can be ideal for use in a patient with a noted Mullerian duct anomaly. Identification of dual collecting ducts or additional renal anomalies is vital to complete hysterectomy safely in these patients, specifically if a uterine anomaly is not recognized prior to surgical intervention.

Impact of referral pattern and timing of repair on surgical outcome after reconstruction of post-cholecystectomy bile duct injury: A multicenter study

BackgroundBile duct injury (BDI) after cholecystectomy remains a significant surgical challenge. No guideline exists to guide the timing of repair, while few studies compare early versus late repair BDI. This study aimed to analyze the outcomes in patients undergoing immediate, intermediate, and delayed repair of BDI. MethodsWe retrospectively analyzed 412 patients with BDI from March 2015 to January 2020. The patients were divided into three groups based on the time of BDI reconstruction. Group 1 underwent an immediate reconstruction (within the first 72 hours post-cholecystectomy, n = 156); group 2 underwent an intermediate reconstruction (from 4 days to 6 weeks post-cholecystectomy, n = 75), and group 3 underwent delayed reconstruction (after 6 weeks post-cholecystectomy, n = 181). ResultsPatients in group 2 had significantly more early complications including anastomotic leakage and intra-abdominal collection and late complications including anastomotic stricture and secondary liver cirrhosis compared with groups 1 and 3. Favorable outcome was observed in 111 (71.2%) patients in group 1, 31 (41.3%) patients in group 2, and 157 (86.7%) patients in group 3 (P = 0.0001). Multivariate analysis identified that complete ligation of the bile duct, level E1 BDI and the use of external stent were independent factors of favorable outcome in group 1, the use of external stent was an independent factor of favorable outcome in group 2, and level E4 BDI was an independent factor of unfavorable outcome in group 3. Transected BDI and level E4 BDI were independent factors of unfavorable outcome. ConclusionsFavorable outcomes were more frequently observed in the immediate and delayed reconstruction of post-cholecystectomy BDI. Complete ligation of the bile duct, level E1 BDI and the use of external stent were independent factors of a favorable outcome.

Изучение нового производного бензимидазола, имеющего в своей структуре пространственно затрудненный фенольный заместитель, на моделях артериального и венозного тромбоза

Введение: Тромбоциты являются ключевыми медиаторами патогенеза артериальных тромбозов и атеросклероза. Поэтому изучение антиагрегантных средств на предмет антитромботической активности на различных моделях артериальных и венозных тромбозов является актуальным. Цель исследования: изучение антитромботической активности соединения РУ-1144 (производного бензимидазола) в сравнении с ацетилсалициловой кислотой (АСК) и клопидогрелом на моделях артериального и венозного тромбозов. Материалы и методы: Артериальный тромбоз моделировали на сонной артерии крыс-самцов аппликацией постоянного электрического тока. Воздействие на сосуд выполняли до момента полной окклюзии, регистрируемой на мониторе доплерографа. Венозной тромбоз моделировали на крысах-самцах полной перевязкой нижней полой вены на 24 ч; через сутки проводили изъятие тромба из сосуда и его взвешивание. В экспериментальных группах животным внутрижелудочно вводили соединение РУ-1144 и препараты сравнения — АСК и клопидогрел, в контрольной группе животным внутрижелудочно вводили дистиллированную воду. Для подтверждения отсутствия влияния хирургических манипуляций на организм животного в исследование модели венозного тромбоза была включена группа ложнооперированных крыс. Результаты: На модели артериального тромбоза установлена более высокая антитромботическая активность соединения РУ-1144 по сравнению с АСК и клопидогрелом в 2,5 и 7,4 раза соответственно. В модели венозного тромбоза соединение РУ-1144 уменьшало среднюю массу венозных тромбов в 5,3 раза по сравнению с группой контроля и превосходило по антитромботической активности АСК и клопидогрел в 3,5 и 1,9 раза. Заключение: Соединение РУ-1144 способно предотвращать патологические процессы, связанные с тромбообразованием, не только в сонной артерии, но и в нижней полой вене. Background: Platelets are key mediators of the pathogenesis of arterial thrombosis and atherosclerosis. So, that is actual to study antithrombotic activity of antiplatelet agents in various models of arterial and venous thromboses. Objectives: to study the antithrombotic activity of RU-1144 compound (benzimidazole derivative) as compared with acetylsalicylic acid (ASA) and clopidogrel on models of arterial and venous thromboses. Materials/Methods: Arterial thrombosis was modeled on the carotid artery of male rats by application of direct electric current. Exposure was performed until full vessel occlusion recorded by Dopplerograf. Venous thrombosis was modeled on male rats by complete ligation of vena cava inferior for 24 hours; a day later the thrombus was removed from the vessel and weighed. In the experimental groups the animals were injected intragastrically with the compound RU-1144 and the comparison drugs — ASA and clopidogrel; in the control group the animals were administered distilled water intragastrically. To confirm the absence of the effect of surgical manipulations on the animal’s organism, a group of false-operated rats was included in the study of venous thrombosis model. Results: In arterial thrombosis model RU-1144 compound had a higher antithrombotic activity as compared with ASA and clopidogrel by 2.5 and 7.4 times, respectively. In venous thrombosis model RU-1144 compound reduced the average weight of venous clots by 5.3 times as compared with the control group and exceeded antithrombotic activity of ASA and clopidogrel by 3.5 and 1.9 times. Conclusions: RU-1144 compound capable to prevent the pathological processes associated with thrombus formation in carotid artery as well as in vena cava inferior.

Utility of urinary organic anion transporter 5 as an early biomarker of obstructive nephropathy.

Ureteral obstruction is a relevant cause of kidney damage. The traditional parameters used in clinical practice for the detection of renal injury are insensitive and non-specific for the diagnosis of obstructive renal disease. The organic anion transporter 5 (Oat5) is a carrier expressed exclusively in the kidney. In this study, the Oat5 urinary excretion (Oat5u ) was evaluated as a potential biomarker of obstructive nephropathy, comparing it with traditional markers of renal function and with neutrophil gelatinase-associated lipocalin in urine (NGALu ), a more recent biomarker of renal pathology. Bilateral ureteral obstruction (BUO) was induced in male Wistar rats, by complete ligation of ureters for 1hour (BUO1), 2hours (BUO2), 5hours (BUO5), or 24hours (BUO24). After 24hours of ureteral releasing, urea and creatinine plasma concentrations, creatinine clearance, urinary total proteins, urinary glucose, and alkaline phosphatase activities in urine were evaluated. Oat5 and NGAL levels were assessed in urine samples by immunoblotting. All parameters of renal function were altered in the BUO24 and some also in BUO5, while the Oat5u increased in all of the experimental groups analyzed. After a long time of ureteral obstruction (BUO24), the urinary excretion of Oat5 markedly increased, in parallel with the alteration in the other parameters evaluated. Nevertheless, in BUO1 and BUO2, Oat5u appeared as the only parameter modified. Therefore, Oat5u could be proposed as a novel early biomarker of ureteral obstruction, with the additional potential to inform about the severity of the obstructive injury suffered by the kidney.