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1.
Eur Rev Med Pharmacol Sci ; 25(3): 1680-1683, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33629338

ABSTRACT

OBJECTIVE: Although pulmonary involvement represents the primary and most characteristic presentation of Sars-Cov-2 infection, due to its innate tropism for endothelium, it is also associated with systemic pro-coagulative changes and thromboses. This paper describes a COVID-19 atypical presentation with massive thrombotic occlusion of the splenoportal-mesenteric axis and the splenic artery in the absence of clinical or radiological manifestation of pulmonary involvement. PATIENTS AND METHODS: Female patient, with no history of disease, trauma or fever in the last 30 days, was admitted to ER for persistent left subcostal pain. Laboratory exams, including inflammation, coagulation markers and Sars-CoV-2 serology, were requested. Whole-body CT with contrast media injection was performed. RESULTS: Laboratory exams showed elevated reactive C-protein, bilirubin, γ-GT and D-dimer. Whole-body CT showed: splenic artery occlusion, thrombosis of splenic, mesenteric and portal veins with portal intra-hepatic branches ectasia, juxta-hilar portal cavernomatosis of probable acute onset (absence of signs of chronic hepatopathy and of varices), a hypodense area in the spleen indicating ischemic parenchymal suffering. The patient resulted positive for Sars-CoV-2 IgG, thus in the absence of typical clinics or pulmonary parenchymal abnormality at chest CT. CONCLUSIONS: A case of acute venous thrombosis and arterial occlusion as primary manifestations of COVID-19.


Subject(s)
COVID-19/diagnostic imaging , Mesenteric Vascular Occlusion/diagnostic imaging , Mesenteric Veins/diagnostic imaging , SARS-CoV-2 , Spleen/blood supply , Splenic Artery/diagnostic imaging , Thrombosis/diagnostic imaging , Aged , COVID-19/blood , COVID-19/complications , Diagnosis, Differential , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/etiology , Spleen/diagnostic imaging , Thrombosis/blood , Thrombosis/etiology , Tomography, X-Ray Computed
2.
J Thromb Haemost ; 17(1): 220-231, 2019 01.
Article in English | MEDLINE | ID: mdl-30444570

ABSTRACT

Essentials Shp2 negatively regulates thrombus stability under pathological shear rate. Shp2 suppresses TXA2 receptor-mediated platelet dense granule secretion. Through αIIbß3 outside-in signaling, Shp2 targets calmodulin-dependent activation of Akt. Shp2 may serve to prevent the formation of unwanted occlusive thrombi. SUMMARY: Background Perpetuation is the final phase of thrombus formation; however, its mechanisms and regulation are poorly understood. Objective To investigate the mechanism of Shp2 in platelet function and thrombosis. Methods and results We demonstrate that the platelet-expressed Src homology region 2 domain-containing protein tyrosine phosphatase Shp2 is a negative regulator of thrombus stability under high shear stress. In a ferric chloride-induced mesenteric arteriole thrombosis model, megakaryocyte/platelet-specific Shp2-deficient mice showed less thrombi shedding than wild-type mice, although their occlusion times were comparable. In accordance with this in vivo phenotype, a microfluidic whole-blood perfusion assay revealed that the thrombi formed on collagen surfaces by Shp2-deficient platelets were more stable under high shear rates than those produced by wild-type platelets. Whereas Shp2 deficiency did not alter platelet responsiveness towards thrombin, ADP and collagen stimulation, Shp2-deficient platelets showed increased dense granule secretion when stimulated by the thromboxane A2 analog U46619. Shp2 appears to act downstream of integrin αIIb ß3 outside-in signaling, inhibiting the phosphorylation of Akt (Ser473 and Thr308) and dense granule secretion. Calmodulin was also shown to bind both Shp2 and Akt, linking Shp2 to Akt activation. Conclusions Platelet Shp2 negatively regulates thrombus perpetuation under high shear stress. This signaling pathway may constitute an important mechanism for the prevention of unwanted occlusive thrombus formation, without dramatically interfering with hemostasis.


Subject(s)
Blood Platelets/enzymology , Mesenteric Vascular Occlusion/enzymology , Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism , Thrombosis/enzymology , Animals , Calmodulin/blood , Disease Models, Animal , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/genetics , Mesenteric Vascular Occlusion/physiopathology , Mice, Knockout , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Protein Binding , Protein Tyrosine Phosphatase, Non-Receptor Type 11/deficiency , Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics , Proto-Oncogene Proteins c-akt/blood , Receptors, Thromboxane A2, Prostaglandin H2/blood , Signal Transduction , Splanchnic Circulation , Stress, Mechanical , Thrombosis/blood , Thrombosis/genetics , Thrombosis/physiopathology
3.
Ann Vasc Surg ; 49: 115-122, 2018 May.
Article in English | MEDLINE | ID: mdl-29428537

ABSTRACT

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been shown to be valuable prognostic markers for a variety of pathological conditions including solid tumors, sepsis, and others. However, the prognostic values of the NLR and PLR in patients with acute mesenteric arterial embolism (AMAE) and acute mesenteric arterial thrombosis (AMAT) have not been elucidated. The aim of this study was to determine the predictive value of the NLR and PLR for poor prognosis in patients with AMAE and AMAT. METHODS: A total of 137 patients with AMAE (n = 77) or AMAT (n = 60) were divided into a poor outcome group (cases of intestinal necrosis or death) and a better outcome group (cases without intestinal necrosis who survived successfully), according to prognosis. Neutrophil, platelet, and lymphocyte counts were recorded before pharmacotherapy or surgery. The NLR and PLR were calculated, and logistic regression analysis was performed to test their prognostic values. RESULTS: The cutoff values for NLR and PLR were 11.05 and 156.26, respectively. The PLR was linearly associated with the NLR (R = 0.769, P < 0.001). NLR (odds ratio [OR] = 6.835, 95% confidence interval [CI] = 2.282-20.469, P = 0.001), PLR (OR = 4.871, 95% CI = 1.627-14.587, P = 0.005), and coronary heart disease (OR = 3.388, 95% CI = 1.156-9.929, P = 0.026) were found to be independent prognostic factors for the patients. CONCLUSIONS: NLR ≥ 11.05, PLR ≥ 156.26, and coronary heart disease were shown to be risk factors for poor prognosis in patients with AMAE and AMAT. According to these factors, patients can be divided into 3 prognostic groups: good, NLR < 11.05 with PLR < 156.26; moderate, NLR < 11.05 with PLR ≥ 156.26 or NLR ≥ 11.05 with PLR < 156.26; and poor, NLR ≥ 11.05 with PLR ≥ 156.26.


Subject(s)
Blood Platelets , Embolism/blood , Mesenteric Ischemia/blood , Mesenteric Vascular Occlusion/blood , Neutrophils , Thrombosis/blood , Adult , Aged , Aged, 80 and over , Area Under Curve , Chi-Square Distribution , Embolism/diagnostic imaging , Embolism/mortality , Embolism/pathology , Female , Humans , Logistic Models , Lymphocyte Count , Lymphocytes , Male , Mesenteric Ischemia/diagnostic imaging , Mesenteric Ischemia/mortality , Mesenteric Ischemia/pathology , Mesenteric Vascular Occlusion/diagnostic imaging , Mesenteric Vascular Occlusion/mortality , Mesenteric Vascular Occlusion/pathology , Middle Aged , Necrosis , Odds Ratio , Platelet Count , Predictive Value of Tests , Prognosis , ROC Curve , Retrospective Studies , Risk Factors , Thrombosis/diagnostic imaging , Thrombosis/mortality , Thrombosis/pathology , Tomography, X-Ray Computed
4.
Am J Gastroenterol ; 112(4): 597-605, 2017 04.
Article in English | MEDLINE | ID: mdl-28266590

ABSTRACT

OBJECTIVES: To identify predictive factors for irreversible transmural intestinal necrosis (ITIN) in acute mesenteric ischemia (AMI) and establish a risk score for ITIN. METHODS: This single-center prospective cohort study was performed between 2009 and 2015 in patients with AMI. The primary outcome was the occurrence of ITIN, confirmed by specimen analysis in patients who underwent surgery. Patients who recovered from AMI with no need for intestinal resection were considered not to have ITIN. Clinical, biological and radiological data were compared in a Cox regression model. RESULTS: A total of 67 patients were included. The origin of AMI was arterial, venous, or non-occlusive in 61%, 37%, 2% of cases, respectively. Intestinal resection and ITIN concerned 42% and 34% of patients, respectively. Factors associated with ITIN in multivariate analysis were: organ failure (hazard ratio (HR): 3.1 (95% confidence interval (CI): 1.1-8.5); P=0.03), serum lactate levels >2 mmol/l (HR: 4.1 (95% CI: 1.4-11.5); P=0.01), and bowel loop dilation on computerized tomography scan (HR: 2.6 (95% CI: 1.2-5.7); P=0.02). ITIN rate increased from 3% to 38%, 89%, and 100% in patients with 0, 1, 2, and 3 factors, respectively. Area under the receiver operating characteristics curve for the diagnosis of ITIN was 0.936 (95% CI: 0.866-0.997) depending on the number of predictive factors. CONCLUSIONS: We identified three predictive factors for irreversible intestinal ischemic injury requiring resection in the setting of AMI. Close monitoring of these factors could help avoid unnecessary laparotomy, prevent resection, as well as complications due to unresected necrosis, and possibly lower the overall mortality.


Subject(s)
Infarction/etiology , Intestinal Diseases/etiology , Intestinal Perforation/etiology , Intestines/pathology , Mesenteric Ischemia/complications , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Area Under Curve , Cohort Studies , Digestive System Surgical Procedures , Female , Humans , Infarction/blood , Infarction/surgery , Intestinal Diseases/blood , Intestinal Diseases/diagnostic imaging , Intestinal Diseases/surgery , Intestinal Perforation/surgery , Intestines/diagnostic imaging , Intestines/surgery , Lactic Acid/blood , Male , Mesenteric Ischemia/blood , Mesenteric Ischemia/diagnostic imaging , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/complications , Mesenteric Vascular Occlusion/diagnostic imaging , Middle Aged , Multiple Organ Failure/etiology , Multivariate Analysis , Necrosis/etiology , Necrosis/surgery , Proportional Hazards Models , Prospective Studies , ROC Curve , Risk Assessment , Tomography, X-Ray Computed , Young Adult
5.
Vascular ; 25(2): 163-169, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27278523

ABSTRACT

Background The diagnosis of acute mesenteric ischemia is variable. Early diagnosis is important for reducing the mortality and morbidity rates. Aim This experimental study aims to investigate the diagnostic utility of D-dimer and neopterin as a marker for the early stage of acute mesenteric ischemia caused by occlusion of superior mesenteric artery. Methods The levels of D-dimer and neopterin were measured using an animal acute mesenteric ischemia model in 21 male rabbits. Superior mesenteric artery occlusion (Group 1, n = 14) and control (Group 2, n = 7) groups were identified. Blood samples at different times are collected from each rabbits. Blood samples from superior mesenteric artery occlusion group were taken 30 min after anesthesia but before laparotomy, 1, 2, and 3 h after superior mesenteric artery ligation. Blood samples from control group were taken 1 h before, 1 and 3 h after anesthesia and laparotomy. The D-dimer and neopterin levels of each blood sample were measured. Results The probability of acute mesenteric ischemia was found to be 36 times higher when the D-dimer level was over 0.125 ng/L, whereas the probability was 19.2 times higher when the neopterin level was over 1.25 nmol/L. Conclusions In this experimental study, the combined elevation of two significant markers, D-dimer and neopterin, may be helpful for the early diagnosis of acute mesenteric ischemia.


Subject(s)
Fibrin Fibrinogen Degradation Products/metabolism , Mesenteric Ischemia/blood , Mesenteric Ischemia/diagnosis , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/diagnosis , Neopterin/blood , Acute Disease , Animals , Area Under Curve , Biomarkers/blood , Disease Models, Animal , Early Diagnosis , Ligation , Male , Mesenteric Artery, Superior/surgery , Mesenteric Ischemia/etiology , Mesenteric Vascular Occlusion/etiology , Predictive Value of Tests , ROC Curve , Rabbits , Time Factors , Up-Regulation
6.
Thromb Haemost ; 117(1): 44-56, 2017 01 05.
Article in English | MEDLINE | ID: mdl-27904902

ABSTRACT

Currently, anticoagulants would be used to prevent thrombosis. Thrombin is an effector enzyme for haemostasis and thrombosis. We designed a direct thrombin inhibitor peptide (DTIP) using molecular simulation and homology modelling and demonstrated that the C-terminus of DTIP interacts with exosite I, and N-terminus with the activity site of thrombin, respectively. DTIP interfered with thrombin-mediated coagulation in human, rat and mouse plasma (n=10 per group) and blocked clotting in human whole blood in vitro. When administered subcutaneously, DTIP showed potent and dose-dependent extension of aPTT, PT, TT and CT in rats (n=10 per group). The antithrombotic dose of DTIP induced significantly less bleeding than bivalirudin determined by transecting distal tail assay in rats. Furthermore, DTIP reached peak blood concentration in 0.5-1 hour and did not cause increased bleeding after five days of dosing compared to dabigatran etexilate. The antithrombotic effect of DTIP was evaluated in mice using lethal pulmonary thromboembolism model and FeCl3-induced mesenteric arteriole thrombus model. DTIP (1.0 mg/kg, sc) prevented deep venous thrombosis and increased the survival rate associated with pulmonary thromboembolism from 30 % to 80 %. Intravital microscopy showed that DTIP (1.0 mg/kg, sc) decelerated mesenteric arteriole thrombosis caused by FeCl3 injury. These data establish that DTIP is a novel antithrombotic agent that could be used to prevent thrombosis without conferring an increased bleeding risk.


Subject(s)
Antithrombins/administration & dosage , Blood Coagulation/drug effects , Hirudins/administration & dosage , Mesenteric Vascular Occlusion/prevention & control , Pulmonary Embolism/prevention & control , Thrombin/antagonists & inhibitors , Venous Thrombosis/prevention & control , Animals , Antithrombins/toxicity , Blood Coagulation Tests , Chlorides , Collagen , Dabigatran/administration & dosage , Dabigatran/toxicity , Disease Models, Animal , Dose-Response Relationship, Drug , Epinephrine , Ferric Compounds , Hemorrhage/chemically induced , Hirudins/toxicity , Humans , Injections, Subcutaneous , Male , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/chemically induced , Mice, Inbred C57BL , Peptide Fragments/administration & dosage , Peptide Fragments/toxicity , Pulmonary Embolism/blood , Pulmonary Embolism/chemically induced , Rats, Sprague-Dawley , Recombinant Proteins/administration & dosage , Recombinant Proteins/toxicity , Risk Factors , Thrombin/metabolism , Time Factors , Venous Thrombosis/blood , Venous Thrombosis/chemically induced
7.
World J Gastroenterol ; 21(47): 13250-8, 2015 Dec 21.
Article in English | MEDLINE | ID: mdl-26715807

ABSTRACT

AIM: To determine the potential protective role of adiponectin in intestinal ischemia reperfusion (I/R) injury. METHODS: A rat model of intestinal I/R injury was established. The serum level of adiponectin in rats with intestinal I/R injury was determined by enzyme-linked immunosorbent assay (ELISA). The serum levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α were also measured by ELISA. Apoptosis of intestinal cells was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The production of malondialdehyde (MDA) and superoxide dismutase (SOD) and villous injury scores were also measured. RESULTS: Adiponectin was downregulated in the serum of rats with intestinal I/R injury compared with sham rats. No significant changes in the expression of adiponectin receptor 1 and adiponectin receptor 2 were found between sham and I/R rats. Pre-treatment with recombinant adiponectin attenuated intestinal I/R injury. The production of pro-inflammatory cytokines, including IL-6, IL-1ß, and TNF-α, in rats with intestinal I/R injury was reduced by adiponectin pre-treatment. The production of MDA was inhibited, and the release of SOD was restored by adiponectin pre-treatment in rats with intestinal I/R injury. Adiponectin pre-treatment also inhibited cell apoptosis in these rats. Treatment with the AMP-activated protein kinase (AMPK) signaling pathway inhibitor, compound C, or the heme oxygenase 1 (HO-1) inhibitor, Snpp, attenuated the protective effects of adiponectin against intestinal I/R injury. CONCLUSION: Adiponectin exhibits protective effects against intestinal I/R injury, which may involve the AMPK/HO-1 pathway.


Subject(s)
Adiponectin/administration & dosage , Gastrointestinal Agents/administration & dosage , Intestinal Mucosa/metabolism , Mesenteric Ischemia/complications , Mesenteric Vascular Occlusion/complications , Reperfusion Injury/prevention & control , AMP-Activated Protein Kinases/metabolism , Adiponectin/blood , Animals , Apoptosis , Biomarkers/blood , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Heme Oxygenase (Decyclizing)/metabolism , Inflammation Mediators/blood , Interleukin-1beta/blood , Interleukin-6/blood , Intestines/blood supply , Intestines/pathology , Malondialdehyde/metabolism , Mesenteric Ischemia/blood , Mesenteric Ischemia/pathology , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/pathology , Rats, Wistar , Recombinant Proteins/administration & dosage , Reperfusion Injury/blood , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Signal Transduction , Superoxide Dismutase/metabolism , Time Factors , Tumor Necrosis Factor-alpha/blood
8.
Thromb Haemost ; 113(4): 870-80, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25427855

ABSTRACT

Factor VII (FVII) activating protease (FSAP) is a circulating protease with a putative function in blood coagulation and fibrinolysis. Genetic epidemiological studies have implied a role for FSAP in carotid stenosis, stroke and thrombosis. To date, no in vivo evidence is available to support these claims. We have, for the first time, used FSAP-/- mice to define its role in thrombosis and haemostasis in vivo and to characterise the molecular mechanisms involved. FeCl3-induced arterial thrombosis in carotid and mesenteric artery revealed that the occlusion time was significantly increased in FSAP-/- mice (p< 0.01) and that some FSAP-/- mice did not occlude at all. FSAP-/- mice were protected from lethal pulmonary thromboembolism induced by collagen/ epinephrine infusion (p< 0.01). Although no spontaneous bleeding was evident, in the tail bleeding assay a re-bleeding pattern was observed in FSAP-/- mice. To explain these observations at a mechanistic level we then determined how haemostasis factors and putative FSAP substrates were altered in FSAP-/- mice. Tissue factor pathway inhibitor (TFPI) levels were higher in FSAP-/- mice compared to WT mice whereas FVIIa levels were unchanged. Other coagulation factors as well as markers of platelet activation and function revealed no significant differences between WT and FSAP-/- mice. This phenotype of FSAP-/- mice could be reversed by application of exogenous FSAP. In conclusion, a lack of endogenous FSAP impaired the formation of stable, occlusive thrombi in mice. The underlying in vivo effect of FSAP is more likely to be related to the modulation of TFPI rather than FVIIa.


Subject(s)
Carotid Artery Diseases/prevention & control , Hemostasis , Mesenteric Vascular Occlusion/prevention & control , Serine Endopeptidases/deficiency , Thrombosis/prevention & control , Venous Thromboembolism/enzymology , Animals , Blood Coagulation Tests , Carotid Arteries/enzymology , Carotid Artery Diseases/blood , Carotid Artery Diseases/chemically induced , Carotid Artery Diseases/enzymology , Carotid Artery Diseases/genetics , Chlorides , Collagen , Disease Models, Animal , Ferric Compounds , Genetic Predisposition to Disease , Hemostasis/genetics , Jugular Veins/enzymology , Lipoproteins/blood , Mesenteric Arteries/enzymology , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/chemically induced , Mesenteric Vascular Occlusion/enzymology , Mesenteric Vascular Occlusion/genetics , Mice, Inbred C57BL , Mice, Knockout , Norepinephrine , Phenotype , Serine Endopeptidases/administration & dosage , Serine Endopeptidases/genetics , Thrombosis/blood , Thrombosis/chemically induced , Thrombosis/enzymology , Thrombosis/genetics , Venous Thromboembolism/blood , Venous Thromboembolism/chemically induced , Venous Thromboembolism/genetics
9.
Khirurgiia (Mosk) ; (6): 36-42, 2014.
Article in Russian | MEDLINE | ID: mdl-25042189

ABSTRACT

It was proposed the medical and diagnostic tactic in patients with acute mesenteric ischemia on basis of efficiency results of modern laboratory markers and instrumental methods. Positive laboratory D-dimer-test with computed tomography of abdominal organs or abdominal aorta and its branches CT-angiography led to diagnose thrombosis or embolism of mesenteric arteries at early terms and to reduce preoperative period. The authors presented the variant of isolated endovascular intervention in case of superior mesenteric artery thrombosis. This technique may be regarded as the method of choice in the treatment of patients with acute mesenteric ischemia.


Subject(s)
Endovascular Procedures/methods , Mesenteric Arteries , Mesenteric Vascular Occlusion , Peritonitis/prevention & control , Abdominal Cavity/diagnostic imaging , Aged , Angiography/methods , Early Diagnosis , Early Medical Intervention , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Intestines/blood supply , Male , Mesenteric Arteries/pathology , Mesenteric Arteries/surgery , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/complications , Mesenteric Vascular Occlusion/diagnosis , Mesenteric Vascular Occlusion/surgery , Middle Aged , Peritonitis/etiology , Tomography, X-Ray Computed/methods , Treatment Outcome , Ultrasonography/methods
10.
Exp Clin Transplant ; 12(3): 246-52, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24907727

ABSTRACT

OBJECTIVES: The purpose of this study was to evaluate the effect of intravenous injection of osthole on intestinal ischemia-reperfusion injury and parameters of oxidative stress. MATERIALS AND METHODS: In 45 Kunming male mice, treatment included sham surgery (15 mice); intestinal ischemia-reperfusion injury (clamping of the superior mesenteric artery, 2 h; clamp release, 1 h; 15 mice); or osthole treatment before and after ischemia-reperfusion injury (15 mice). Evaluation included histopathology, determination of intestinal wet/dry weight ratio, and measurement of levels of diamine oxidase, superoxide dismutase, malondialdehyde, interleukin 1ß, tumor necrosis factor α, and interleukin 2. Intestinal barrier permeability was evaluated with Evans blue test. RESULTS: The mean wet-to-dry weight ratio, Evans blue content, and Chiu score were significantly greater in the ischemia-reperfusion than in the sham group and lower in the osthole-treated than the ischemia-reperfusion group. The mean serum diamine oxidase, malondialdehyde, interleukin 1ß, and tumor necrosis factor α levels were significantly greater in the ischemia-reperfusion than in the sham group and lower in the osthole-treated than in the ischemia-reperfusion group. The mean superoxide dismutase activity and interleukin 2 levels were lower in the ischemia-reperfusion than in the sham group and greater in the osthole-treated than in the ischemia-reperfusion group. CONCLUSIONS: Treatment with osthole may protect against oxidative stress and tissue damage from intestinal ischemia-reperfusion injury.


Subject(s)
Antioxidants/pharmacology , Coumarins/pharmacology , Ileum/blood supply , Ileum/drug effects , Mesenteric Ischemia/drug therapy , Mesenteric Vascular Occlusion/drug therapy , Reperfusion Injury/prevention & control , Animals , Antioxidants/administration & dosage , Biomarkers/blood , Coumarins/administration & dosage , Cytoprotection , Disease Models, Animal , Ileum/metabolism , Ileum/pathology , Injections, Intravenous , Male , Mesenteric Ischemia/blood , Mesenteric Ischemia/immunology , Mesenteric Ischemia/pathology , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/immunology , Mesenteric Vascular Occlusion/pathology , Mice , Oxidative Stress/drug effects , Permeability , Reperfusion Injury/blood , Reperfusion Injury/immunology , Reperfusion Injury/pathology
11.
World J Gastroenterol ; 19(43): 7813-5, 2013 Nov 21.
Article in English | MEDLINE | ID: mdl-24282370

ABSTRACT

Mesenteric venous thrombosis (MVT) is a rare but life threatening form of bowel ischemia. It is implicated in 6%-9% of all cases of acute mesenteric ischemia. The proportion of patients with primary (or idiopathic) MVT varies from 0% to 49%, with a decrease in frequency secondary to more recent availability of newer investigations for hypercoagulability. The presence of factor V Leiden (FVL) and prothrombin G20210A mutations (PGM) have been well documented in these cases. However, there have been scarce case reports describing MVT in heterozygotes of both these mutations occurring simultaneously and its implications on long term management. Our case describes acute MVT in a previously asymptomatic young patient with no prior history of venous thromboembolism. The patient was found to be heterozygous for FVL and PGM and treated with lifelong anticoagulation with warfarin (goal international normalized ratio: 2-3) and avoidance of hormonal contraceptives.


Subject(s)
Activated Protein C Resistance/genetics , Blood Coagulation/genetics , Factor V/genetics , Ischemia/genetics , Mesenteric Vascular Occlusion/genetics , Mesenteric Veins , Mutation , Prothrombin/genetics , Vascular Diseases/genetics , Venous Thrombosis/genetics , Activated Protein C Resistance/blood , Activated Protein C Resistance/complications , Activated Protein C Resistance/diagnosis , Activated Protein C Resistance/drug therapy , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , DNA Mutational Analysis , Female , Genetic Predisposition to Disease , Heterozygote , Humans , International Normalized Ratio , Ischemia/blood , Ischemia/diagnosis , Ischemia/drug therapy , Mesenteric Ischemia , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/diagnosis , Mesenteric Vascular Occlusion/drug therapy , Phenotype , Phlebography/methods , Tomography, X-Ray Computed , Vascular Diseases/blood , Vascular Diseases/diagnosis , Vascular Diseases/drug therapy , Venous Thrombosis/blood , Venous Thrombosis/diagnosis , Venous Thrombosis/drug therapy , Warfarin/therapeutic use , Young Adult
12.
World J Gastroenterol ; 19(23): 3583-95, 2013 Jun 21.
Article in English | MEDLINE | ID: mdl-23801859

ABSTRACT

AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury. METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent assay. RESULTS: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption. CONCLUSION: Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury.


Subject(s)
Bone Marrow Transplantation , Intestines/blood supply , Mesenchymal Stem Cell Transplantation , Mesenteric Vascular Occlusion/surgery , Mucous Membrane/blood supply , Reperfusion Injury/prevention & control , Tight Junctions/metabolism , Tumor Necrosis Factor-alpha/blood , Zonula Occludens-1 Protein/metabolism , Amine Oxidase (Copper-Containing)/blood , Animals , Biomarkers/blood , Cells, Cultured , Disease Models, Animal , Down-Regulation , Intestinal Mucosa/metabolism , Intestines/immunology , Intestines/ultrastructure , Lactic Acid/blood , Male , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/immunology , Mesenteric Vascular Occlusion/pathology , Mucous Membrane/immunology , Mucous Membrane/metabolism , Mucous Membrane/ultrastructure , Permeability , Rats , Rats, Sprague-Dawley , Reperfusion Injury/blood , Reperfusion Injury/immunology , Reperfusion Injury/pathology , Signal Transduction , Time Factors
13.
Kaohsiung J Med Sci ; 29(3): 119-27, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23465414

ABSTRACT

The aim of this study was to test the hypothesis that postconditioning (POC) would reduce the detrimental effects of the acute intestinal ischemia-reperfusion (I/R) compared to those of the abrupt onset of reperfusion. POC has a protective effect on intestinal I/R injury by inhibiting events in the early minutes of reperfusion in rats. Twenty-four Wistar-Albino rats were subjected to the occlusion of superior mesenteric artery for 30 minutes, then reperfused for 120 minutes, and randomized to the four different modalities of POC: (1) control (no intervention); (2) POC-3 (three cycles of 10 seconds of reperfusion-reocclusion, 1 minute total intervention); (3) POC-6 (six cycles of 10 seconds of reperfusion-reocclusion, 2 minutes total intervention); and (4) sham operation (laparotomy only). The arterial blood samples [0.3 mL total creatine kinase (CK) and 0.6 mL malondialdehyde (MDA)] and the intestinal mucosal MDA were collected from each after reperfusion. POC, especially POC-6, was effective in attenuating postischemic pathology by decreasing the intestinal tissue MDA levels, serum total CK activity, inflammation, and total histopathological injury scores. POC exerted a protective effect on the intestinal mucosa by reducing the mesenteric oxidant generation, lipid peroxidation, and neutrophil accumulation. The six-cycle algorithm demonstrated the best protection.


Subject(s)
Intestinal Mucosa/pathology , Mesenteric Artery, Superior/pathology , Mesenteric Vascular Occlusion/pathology , Reperfusion Injury/pathology , Animals , Creatine Kinase/blood , Intestinal Mucosa/metabolism , Lipid Peroxidation , Male , Malondialdehyde/blood , Mesenteric Artery, Superior/metabolism , Mesenteric Vascular Occlusion/blood , Neutrophil Infiltration , Rats , Rats, Wistar , Reperfusion Injury/blood
14.
World J Gastroenterol ; 19(6): 882-8, 2013 Feb 14.
Article in English | MEDLINE | ID: mdl-23430966

ABSTRACT

AIM: To determine the splanchnic blood flow and oxygen uptake in healthy-subjects and patients and to relate the findings to body-composition. METHODS: The total splanchnic blood flow (SBF) and oxygen uptake (SO2U) were measured in 20 healthy volunteers (10 women) and 29 patients with suspected chronic intestinal ischemia (15 women), age 40-85 years, prior to and after a standard meal. The method is based on the Fick principle using the continuous infusion of an indicator (99mTechnetium-labelled mebrofenin) and catheterization of an artery and the hepatic vein. An angiography of the intestinal arteries was performed during the same investigation. A whole-body dual-energy x-ray absorptiometry scan was performed in healthy volunteers to determine body composition. RESULTS: Angiography revealed no atherosclerotic lesions in the intestinal arteries. The mean baseline SBF was 1087 mL/min (731-1390), and this value increased significantly to 1787 mL/min after the meal in healthy volunteers (P < 0.001). The baseline SBF in patients was 1080 mL/min, which increased to 1718 mL/min postprandially (P < 0.001). The baseline SBF was independent of age, sex, lean body mass and percentage of body fat. The mean meal-induced increase in SBF was equal to 282 mL/min + 5.4 mL/min × bodyweight, (P = 0.025). The SO2U in healthy volunteers and patients was 50.7 mL/min and 48.0 mL/min, respectively, and these values increased to 77.5 mL/min and 75 mL/min postprandially, respectively. Both baseline and postprandial SO2U were directly related to lean body mass. Age and sex exerted no impact on SO2U. CONCLUSION: A direct correlation between body weight and the postprandial increase in SBF was observed. The effect of body weight should be considered in the diagnosis of chronic intestinal ischemia.


Subject(s)
Body Composition , Ischemia/physiopathology , Mesenteric Vascular Occlusion/physiopathology , Splanchnic Circulation , Vascular Diseases/physiopathology , Absorptiometry, Photon , Adult , Aged , Aged, 80 and over , Aniline Compounds , Body Weight , Case-Control Studies , Female , Glycine , Humans , Imino Acids , Ischemia/blood , Ischemia/diagnosis , Linear Models , Male , Mesenteric Arteries/diagnostic imaging , Mesenteric Arteries/physiopathology , Mesenteric Ischemia , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/diagnosis , Middle Aged , Organotechnetium Compounds , Oxygen Consumption , Postprandial Period , Predictive Value of Tests , Radiopharmaceuticals , Reference Values , Regional Blood Flow , Vascular Diseases/blood , Vascular Diseases/diagnosis
15.
Biomarkers ; 18(2): 116-20, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23312006

ABSTRACT

OBJECTIVE: To investigate the predictive value of serum nitrate (nitrogen oxide: NOx) levels in the detection of peripheral and mesenteric ischaemia durations. METHODS: Rats were sacrificed for determining the basal serum values of NOx in Group I without any intervention. The superior mesenteric artery was clamped in Groups II and III and blood samples were taken at 120 minutes in Group II and at 360 minutes in Group III. The right common femoral artery was clamped in Groups IV and V and blood samples were taken at 120 minutes in Group IV and at 360 minutes in Group V. RESULTS: The peak values of NOx were obtained in Group II and Group IV. NOx levels were reduced in advanced periods of ischaemia. In the other words, the NOx levels were significantly higher at two hours of ischaemia (p < 0.05), and NOx levels were reduced to normal ranges at the sixth hour of ischaemia. CONCLUSION: Early diagnosis and rapid treatment are important for acute ischaemic disorders. Serum NOx levels can be a decisive biomarker for prediction of the critical ischaemia period.


Subject(s)
Ischemia/blood , Mesenteric Vascular Occlusion/blood , Nitric Oxide/blood , Animals , Biomarkers/blood , Constriction , Femoral Artery/surgery , Ischemia/diagnosis , Ischemia/etiology , Male , Mesenteric Artery, Superior/surgery , Mesenteric Vascular Occlusion/complications , Mesenteric Vascular Occlusion/diagnosis , Predictive Value of Tests , Rats , Rats, Sprague-Dawley
17.
J Emerg Med ; 42(6): 741-7, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21871766

ABSTRACT

BACKGROUND: Acute intestinal ischemia is a serious clinical disorder with mesenteric infarction, which has high mortality. It is important to establish a biochemical marker for the early diagnosis of acute intestinal ischemia. OBJECTIVES: The aim of this experimental study was to assess the changes in the serum levels of intestinal fatty acid binding protein (IFABP) and phosphate by time using the acute intestinal ischemia model in rabbits. METHODS: In this study, 21 New Zealand rabbits were randomly divided into three groups. Blood samples were obtained at 0, 1, 3, and 6 h in the control group. Blood samples were obtained at 0, 1, 3, and 6 h in the sham group after simple laparotomy. Blood samples were obtained at the same hours in the ischemia group after simple laparotomy and ligation of the superior mesenteric artery. RESULTS: There was no significant difference between the control, the sham, and the ischemia groups in terms of serum IFABP levels at any time (p > 0.05). Serum phosphate levels significantly increased in the ischemia group (p < 0.001). Studies on IFABP have begun emerging in the literature, and there is no standard approach for the technique to measure the IFABP level. No studies on IFABP were found in the literature on rabbits. CONCLUSION: Based on our results, the role that IFABP levels play in the diagnosis of acute intestinal ischemia is unclear at this time. Serum phosphate levels continued to rise as the duration of ischemia was prolonged. These findings support the suggestion that serum phosphate levels are valuable for the diagnosis of acute intestinal ischemia.


Subject(s)
Fatty Acid-Binding Proteins/blood , Ischemia/diagnosis , Mesenteric Vascular Occlusion/blood , Phosphates/blood , Acute Disease , Animals , Biomarkers/blood , Disease Models, Animal , Rabbits
18.
Ulus Travma Acil Cerrahi Derg ; 17(3): 193-8, 2011 May.
Article in English | MEDLINE | ID: mdl-21935794

ABSTRACT

BACKGROUND: In this study, using an animal model of acute mesenteric ischemia (AMI), we investigated the possible use of procalcitonin and phosphorus in the early diagnosis of AMI. METHODS: In this study, 21 New Zealand rabbits were used. Subjects were allocated into three groups as Control, Sham and Ischemia. No intervention was performed in the subjects in the Control group. In the subjects in the Sham and Ischemia groups, laparotomy was performed with midline incision. In the Ischemia group, the superior mesenteric artery was found and tied after laparotomy. Blood was drawn from the animals in all groups at 0, 1, 3 and 6 hours, and procalcitonin and phosphorus levels were studied in these samples. RESULTS: In the Ischemia group, the increase in the levels of serum phosphorus and procalcitonin was found to be statistically significant compared to the Control and Sham groups (p<0.05). The levels of phosphorus and procalcitonin were detected to increase from the 1st hour after ischemia onset, and the increase continued for the following 6 hours (p<0.05). CONCLUSION: Phosphorus and procalcitonin may be important parameters for use in the early diagnosis and prognosis of AMI.


Subject(s)
Calcitonin/blood , Glycoproteins/blood , Mesenteric Vascular Occlusion/diagnosis , Phosphorus/blood , Protein Precursors/blood , Acute Disease , Animals , Disease Models, Animal , Ischemia/blood , Ischemia/diagnosis , Mesenteric Arteries , Mesenteric Vascular Occlusion/blood , Predictive Value of Tests , Prognosis , Rabbits
19.
Mol Med Rep ; 4(6): 1095-9, 2011.
Article in English | MEDLINE | ID: mdl-21842126

ABSTRACT

Early diagnosis of acute mesenteric ischemia (AMI) remains very difficult, partly due to the fact that useful markers of early small bowel ischemia have not yet been identified. Thus, in this study, we aimed to evaluate the levels of serum intracellular enzymes in the tissues and organs in a controlled animal model of mesenteric intestinal ischemia. Forty-eight New Zealand rabbits were divided into 4 groups including the control, artery ligation, vein ligation, and both artery and vein ligation groups. Plasma samples were obtained at 0-, 1-, 3-, 6- and 9-h time-points and enzyme levels were determined. The bowel color and vitality were observed at the same time. The bowel showed an appearance of infarction after a period of ischemia in the animals. Six and 9 h after superior mesenteric artery ischemia, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels increased significantly. However, after 3 h of superior mesenteric venous (SMV) ligation, γ-glutamyl transpeptidase levels in the blood were considerably higher compared to the control group. Six hours after SMV ischemia, ALT, AST, alkaline phosphatase and lactate dehydrogenase levels were significantly elevated compared to those pre-ligation. Serum enzyme levels during intestinal ischemia are not able to provide sufficient information as regards the extent and reversibility of intestinal ischemia, although, they may be able to reflect the presence of injury.


Subject(s)
Enzymes/blood , Ischemia/blood , Mesenteric Vascular Occlusion/blood , Acute Disease , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Animals , Aspartate Aminotransferases/blood , Disease Models, Animal , Female , Intestines/blood supply , Ischemia/diagnosis , L-Lactate Dehydrogenase/blood , Male , Mesenteric Artery, Superior/surgery , Mesenteric Veins/surgery , Rabbits , gamma-Glutamyltransferase/blood
20.
J Gastrointest Surg ; 15(1): 97-100, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20824370

ABSTRACT

BACKGROUND: Vascular thrombotic complications in inflammatory bowel disease (IBD) are well recognized, although mesenteric vascular thrombotic disease is rare. METHODS: We describe nine patients in a tertiary care center with IBD that developed thrombosis of the mesenteric arterial or venous vasculature (e.g., mesenteric thrombosis, MT). RESULTS: Eight subjects developed mesenteric venous thrombosis (five located in the superior mesenteric vein and three located in a branch of the portal vein) and one had a mesenteric arterial embolus, located in the splenic artery. Five subjects had Crohn's disease (CD), and four had ulcerative colitis. The one subject diagnosed with an arterial thrombosis had CD. Mean time from diagnosis of IBD to diagnosis of thrombosis was 24.6 ± 13.5 years. Five of the nine subjects developed mesenteric venous thrombosis while their IBD was clinically in remission. Seven of nine subjects were symptomatic from the development of MT, including bowel infarction that led to development of short bowel syndrome. CONCLUSION: Mesenteric thrombosis is a rare complication of IBD and may develop during clinical remission, suggesting a potential role for factors other than clinically significant inflammation in its pathogenesis.


Subject(s)
Inflammatory Bowel Diseases/complications , Mesenteric Vascular Occlusion/etiology , Thromboembolism/etiology , Adult , Aged , Blood Sedimentation , C-Reactive Protein/metabolism , Female , Follow-Up Studies , Humans , Inflammatory Bowel Diseases/blood , Male , Mesenteric Vascular Occlusion/blood , Mesenteric Vascular Occlusion/diagnosis , Middle Aged , Prognosis , Retrospective Studies , Thromboembolism/blood , Thromboembolism/diagnosis , Young Adult
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