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1.
J Vet Intern Med ; 33(5): 2257-2266, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31512777

RESUMO

BACKGROUND: Plasma adrenocorticotropic hormone (ACTH) and serum cortisol concentrations increase with illness-associated stress. Dynamics of plasma ACTH and serum cortisol concentrations in adult horses with systemic illness are undocumented. HYPOTHESIS/OBJECTIVE: To determine whether ACTH and cortisol concentrations and the ACTH/cortisol ratio vary with survival, the presence of systemic inflammatory response syndrome (SIRS), or ischemic gastrointestinal lesions at admission, or throughout hospitalization. ANIMALS: One hundred fifty-one adult horses. METHODS: Prospective study measuring serum cortisol and plasma ACTH at admission and on days 2, 4, and 6 of hospitalization. Horses were grouped by outcome (survival, SIRS status, number of SIRS criteria [SIRS score], SIRS severity group, and the presence of an ischemic lesion). Differences between groups and over time for ACTH, cortisol, and ACTH/cortisol ratio were investigated with a mixed effect model. Receiving operator characteristic curves and odds ratios were calculated for survival and ischemia. RESULTS: In all groups, ACTH, cortisol, and ACTH/cortisol ratio significantly decreased over time (P < .0001). ACTH, cortisol, and ACTH/cortisol ratio were higher at admission in nonsurvivors, and ACTH and cortisol were higher in horses with ischemic lesions (P < .01). Horses with ACTH above reference interval at admission were 6.10 (2.73-13.68 [95% confidence interval]) times less likely to survive (P < .0001). No significant difference in ACTH, cortisol, and ACTH/cortisol ratio between horses with different SIRS status, scores, or groups were detected, although nonsurvivors had a higher SIRS score (P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Pituitary and adrenal responses are altered in nonsurviving horses and those with an ischemic gastrointestinal lesion.


Assuntos
Gastroenteropatias/veterinária , Doenças dos Cavalos/sangue , Isquemia/veterinária , Síndrome de Resposta Inflamatória Sistêmica/veterinária , Hormônio Adrenocorticotrópico/sangue , Animais , Feminino , Gastroenteropatias/sangue , Cavalos , Hidrocortisona/sangue , Isquemia/sangue , Masculino , Estudos Prospectivos , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/sangue
2.
J Zhejiang Univ Sci B ; 20(8): 687-692, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31273966

RESUMO

The objective of this study was to assess the angiogenic potential expressed as a quotient of vascular endothelial growth factor A (VEGF-A), as an indicator of proangiogenic activity, and the circulating receptors (soluble VEGF receptor protein R1 (sVEGFR-1) and sVEGFR-2), as indicators of the effect of angiogenic inhibition, depending on the concentrations of matrix metalloproteinase 2 (MMP-2) and MMP-9 and their tissue inhibitor 1 (TIMP-1) and TIMP-2 in the plasma of patients with lower extremity artery disease (LEAD). These blood parameters in patients with intermittent claudication (IC) and critical limb ischemia (CLI) were compared for select clinical and biochemical features. Stimulation of angiogenesis in the plasma of individuals with LEAD was evident as indicated by the significant increase in VEGF-A concentration along with reduced inhibition depending on circulating receptors sVEGFR-1 and sVEGFR-2. Critical ischemia was associated with higher VEGF-A, MMP-9, TIMP-1, and TIMP-2 concentrations than in the case of IC.


Assuntos
Claudicação Intermitente/sangue , Isquemia/sangue , Extremidade Inferior/irrigação sanguínea , Metaloproteinase 9 da Matriz/sangue , Neovascularização Patológica , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/sangue , Idoso , Inibidores da Angiogênese/farmacologia , Feminino , Regulação da Expressão Gênica , Humanos , Claudicação Intermitente/tratamento farmacológico , Isquemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue
3.
Oxid Med Cell Longev ; 2019: 7857082, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191804

RESUMO

Intestinal ischemia/reperfusion (I/R), which is associated with high morbidity and mortality, is also accompanied with abnormal energy metabolism and liver injury. Irisin, a novel exercise-induced hormone, can regulate adipose browning and thermogenesis. The following study investigated the potential role of dexmedetomidine in liver injury during intestinal I/R in rats. Adult male Sprague-Dawley rats underwent occlusion of the superior mesenteric artery for 90 min followed by 2 h of reperfusion. Dexmedetomidine or irisin-neutralizing antibody was intravenously administered for 1 h before surgery. The results demonstrated that severe intestine and liver injuries occurred during intestinal I/R as evidenced by pathological scores and an apparent increase in serum diamine oxidase (DAO), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels. In addition, the hepatic irisin, cleaved caspase-3, Bax, and NLRP3 inflammasome components (including NLRP3, ASC, and caspase-1), protein expressions, apoptotic index, reactive oxygen species (ROS), malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 6 levels increased; however, the serum irisin level and hepatic Bcl-2 protein expression and superoxide dismutase (SOD) activity decreased after intestinal I/R. Interestingly, dexmedetomidine could reduce the above listed changes and increase the irisin levels in plasma and the liver in I/R rats. Dexmedetomidine-mediated protective effects on liver injury and NLRP3 inflammasome activation during intestinal I/R were partially abrogated via irisin-neutralizing antibody treatment. The results suggest that irisin might contribute to the hepatoprotection of dexmedetomidine during intestinal ischemia/reperfusion.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Dexmedetomidina/uso terapêutico , Fibronectinas/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/patologia , Isquemia/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Fibronectinas/antagonistas & inibidores , Fibronectinas/sangue , Isquemia/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/sangue , Fator de Necrose Tumoral alfa/metabolismo
5.
Medicine (Baltimore) ; 98(11): e14910, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30882710

RESUMO

The relevance of LP(a), Hcy, and D-D in ischemic cerebrovascular disease remains undefined. This study aimed to assess the associations of plasma LP(a), Hcy and D-D levels with the subtype of ischemic cerebrovascular disease.Patients with ischemic cerebrovascular disease admitted to the Taixing People's Hospital were retrospectively enrolled from November 2017 to July 2018. Immunoturbidimetry was used to assess 119 LAA, 107 SAO, and 112 TIA patients for plasma LP(a), Hcy, and D-D levels.Plasma LP(a), Hcy, and D-D levels in the large artery atherosclerosis (LAA) group were significantly lower than those of the transient ischemic attack (TIA) group (all P < .05). LP(a), Hcy, and D-D levels were significantly reduced in the SAO group compared with the TIA group (both P < .05). The LAA and SAO groups showed comparable values for all the above parameters (P > .05).LP(a), Hcy, and D-D levels differ according to the subtype of ischemic cerebrovascular disease.


Assuntos
Transtornos Cerebrovasculares/sangue , Isquemia/sangue , Acidente Vascular Cerebral/sangue , Idoso , Análise de Variância , Hidrolases de Éster Carboxílico/análise , Hidrolases de Éster Carboxílico/sangue , Transtornos Cerebrovasculares/classificação , Feminino , Humanos , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/sangue , Lipoproteína(a)/análise , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas
6.
J Vasc Surg ; 70(3): 795-805.e1, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30857850

RESUMO

BACKGROUND: It is well known that the clinical outcome of patients with critical limb ischemia (CLI) is poor. However, the relationship between stress-related hormone levels and CLI outcome remains unclear. The aim of this study was to reveal the association of stress hormones with the risk of a perioperative major adverse cardiovascular event (pMACE) in CLI patients undergoing surgical and endovascular revascularization. METHODS: The study analyzed 467 CLI patients who had levels of stress-related hormones (epinephrine, norepinephrine, dopamine, and cortisol) measured before undergoing revascularization. The primary end point was pMACE, including all-cause mortality, myocardial infarction, and stroke within 30 days after revascularization. Propensity score matching was used to try to control for potential confounding. RESULTS: Of the 467 patients analyzed, pMACE was observed in 21 patients (4.5%). The crude comparison of stress-related hormone levels between those with and those without pMACE showed that those with pMACE had a higher level of epinephrine, dopamine, and cortisol compared with those without pMACE. After propensity matching (20 patients with pMACE and 192 patients without pMACE), epinephrine and cortisol levels were significantly higher in those with pMACE. Multivariate analysis confirmed that both epinephrine and cortisol levels were related to the risk of pMACE independently of each other. The Cox proportional hazards regression model demonstrated that both hormones were associated with 30-day mortality but not with longer term mortality. CONCLUSIONS: Stress-related hormone (epinephrine and cortisol) levels were significantly associated with the risk of pMACE in CLI patients undergoing revascularization. Both hormones were related to 30-day mortality.


Assuntos
Procedimentos Endovasculares/efeitos adversos , Epinefrina/sangue , Hidrocortisona/sangue , Isquemia/cirurgia , Infarto do Miocárdio/epidemiologia , Doença Arterial Periférica/cirurgia , Acidente Vascular Cerebral/epidemiologia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Dopamina/sangue , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Isquemia/sangue , Isquemia/diagnóstico , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Norepinefrina/sangue , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/mortalidade
7.
Trials ; 20(1): 101, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717805

RESUMO

BACKGROUND: Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy. METHODS: The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2470 elderly (≥ 70 years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ≤9 g/dl during surgery or within 3 days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb ≤ 9 g/dl with a target range for the post-transfusion Hb level of 9-10.5 g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb ≤ 7.5 g/dl with a target range for the post-transfusion Hb level of 7.5-9 g/dl). The intervention per patient will be followed until hospital discharge or up to 30 days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90 days after surgery. Infections requiring iv antibiotics with re-hospitalisation are assessed as important secondary endpoint. The primary endpoint will be analysed by logistic regression adjusting for age, cancer surgery (y/n), type of surgery (intermediate- or high-risk), and incorporating centres as random effect. DISCUSSION: The LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90 days after surgery. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT03369210 ).


Assuntos
Anemia/terapia , Transfusão de Eritrócitos/métodos , Isquemia/prevenção & controle , Assistência Perioperatória/métodos , Procedimentos Cirúrgicos Operatórios , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/complicações , Anemia/mortalidade , Biomarcadores/sangue , Causas de Morte , Ensaios Clínicos Fase IV como Assunto , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Eritrócitos/mortalidade , Feminino , Alemanha , Hemoglobinas/metabolismo , Humanos , Isquemia/sangue , Isquemia/diagnóstico , Isquemia/etiologia , Masculino , Estudos Multicêntricos como Assunto , Readmissão do Paciente , Assistência Perioperatória/efeitos adversos , Assistência Perioperatória/mortalidade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Procedimentos Cirúrgicos Operatórios/mortalidade , Fatores de Tempo , Resultado do Tratamento
8.
J Vasc Surg ; 69(6): 1924-1935, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30777693

RESUMO

OBJECTIVE: Previous studies have shown that hydrogen sulfide (H2S) exerts potent proangiogenic properties under in vitro conditions and in rodent models. We sought to determine whether a novel H2S prodrug promotes peripheral revascularization in a swine model of acute limb ischemia (ALI). METHODS: ALI was induced in 17 female miniswine via intravascular occlusion of the external iliac. At day 7 after ALI induction, miniswine (n = 17) were randomized to received placebo or the H2S prodrug, SG-1002 (800 mg per os twice a day), for 35 days. At day 35 SG-1002 increased circulating levels of H2S (5.0 ± 1.2 µmol/L vs 1.8 ± 0.50 µmol/L; P < .05), sulfane sulfur (10.6 ± 2.3 µmol/L vs 2.6 ± 0.8 µmol/L; P < .05), and nitrite (0.5 ± 0.05 µmol/L vs 0.3 ± 0.03 µmol/L; P < .005) compared with placebo. SG-1002 therapy increased angiographic scoring in ischemic limb vessel number (27.6 ± 1.6 vs 22.2 ± 1.8; P < .05) compared with placebo. Treatment with SG-1002 preserved existing capillaries in ischemic limbs (128.3 ± 18.7 capillaries/mm2 vs 79.0 ± 9.8 capillaries/mm2; P < .05) compared with placebo. Interestingly, treatment with SG-1002 also improved coronary vasorelaxation responses to bradykinin and substance P in miniswine with ALI. CONCLUSIONS: Our results suggest that daily administration of the H2S prodrug, SG-1002, leads to an increase in circulating H2S and nitric oxide signaling and preserves vessel number and density in ischemic limbs. Furthermore, SG-1002 therapy improved endothelial-dependent coronary artery vasorelaxation in the setting of ALI. Our data demonstrate that SG-1002 preserves the vascular architecture in ischemic limbs and exerts vascular protective effects in the coronary vasculature in a model of peripheral vascular disease.


Assuntos
Indutores da Angiogênese/farmacologia , Extremidades/irrigação sanguínea , Sulfeto de Hidrogênio/farmacologia , Isquemia/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , Doença Arterial Periférica/tratamento farmacológico , Pró-Fármacos/farmacologia , Doença Aguda , Indutores da Angiogênese/sangue , Indutores da Angiogênese/farmacocinética , Animais , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Feminino , Sulfeto de Hidrogênio/sangue , Sulfeto de Hidrogênio/farmacocinética , Isquemia/sangue , Isquemia/fisiopatologia , Óxido Nítrico/sangue , Nitritos/sangue , Estresse Oxidativo/efeitos dos fármacos , Doença Arterial Periférica/sangue , Doença Arterial Periférica/fisiopatologia , Pró-Fármacos/farmacocinética , Fluxo Sanguíneo Regional , Transdução de Sinais , Suínos , Porco Miniatura , Vasodilatação/efeitos dos fármacos
9.
Thromb Res ; 175: 46-52, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30703701

RESUMO

INTRODUCTION: The ultrastructure and cellular composition of thrombi has a profound effect on the outcome of acute ischemic stroke (AIS), coronary (CAD) and peripheral artery disease (PAD). Activated neutrophils release a web-like structure composed mainly of DNA and citrullinated histones, called neutrophil extracellular traps (NET) that modify the stability and lysability of fibrin. Here, we investigated the NET-related structural features of thrombi retrieved from different arterial localizations and their interrelations with routinely available clinical data. PATIENTS AND METHODS: Thrombi extracted from AIS (n = 78), CAD (n = 66) or PAD (n = 64) patients were processed for scanning electron microscopy, (immune)stained for fibrin, citrullinated histone H3 (cH3) and extracellular DNA. Fibrin fiber diameter, cellular components, DNA and cH3 were measured and analyzed in relation to clinical parameters. RESULTS: DNA was least present in AIS thrombi showing a 2.5-fold lower DNA/fibrin ratio than PAD, whereas cH3 antigen was unvaryingly present at all locations. The NET content of thrombi correlated parabolically with systemic inflammatory markers and positively with patients' age. The median platelet content was lower in PAD (2.2%) than in either AIS (3.9%) or CAD (3.1%) and thrombi from smokers contained less platelets than non-smokers. Fibrin fibers were significantly thicker in male patients with CAD (median fiber diameter 76.3 nm) compared to AIS (64.1 nm) or PAD (62.1 nm) and their diameter correlated parabolically with systemic inflammatory markers. CONCLUSIONS: The observed NET-related variations in thrombus structure shed light on novel determinants of thrombus stability that eventually affect both the spontaneous progress and therapeutic outcome of ischemic arterial diseases.


Assuntos
Armadilhas Extracelulares/metabolismo , Isquemia/sangue , Neutrófilos/metabolismo , Doença Arterial Periférica/sangue , Trombose/sangue , Feminino , Humanos , Isquemia/patologia , Masculino , Doença Arterial Periférica/patologia , Trombose/patologia
10.
J Thromb Thrombolysis ; 47(4): 540-549, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30762155

RESUMO

INTRODUCTION: Hypolysible fibrin clots composed of tightly packed fibers characterize patients with peripheral artery disease (PAD) especially those with critical limb ischemia (CLI). Little is known about the impact of a prothrombotic clot phenotype on restenosis following endovascular revascularization in CLI. The goal of this study was to compare fibrin clot properties and their determinants in CLI patients with restenosis after endovascular treatment (ET) and those free of this complication. METHODS: 85 patients with CLI and restenosis within 1 year after ET on optimal pharmacotherapy and 47 PAD control patients without restenosis were included into the study. Plasma fibrin clot permeability (Ks, a measure of the average pore size in the fibrin network) and clot lysis time (CLT) with its potential determinants were determined. During follow-up, the composite endpoint including re-intervention, amputation and death was assessed. RESULTS: Compared with the control group, patients with restenosis had reduced Ks (- 9.5%, p < 0.001), prolonged CLT (+ 12.4%, p = 0.003), higher thrombin generation (+ 7.9%, p < 0.001) and elevated von Willebrand factor (vWF) antigen (+ 14.2%, p < 0.001). During a 24 months follow-up the composite endpoint occurred in 54 CLI patients with restenosis (63.5%) and nine control patients (19.1%, p < 0.001) with no association with baseline Ks and CLT. CONCLUSION: The increased thrombin formation and unfavorable fibrin clot properties occur in patients with CLI who experienced restenosis despite optimal endovascular and pharmacological therapy.


Assuntos
Extremidades/irrigação sanguínea , Fibrina/metabolismo , Oclusão de Enxerto Vascular/terapia , Isquemia/sangue , Trombina/metabolismo , Trombose/sangue , Trombose/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Tempo de Lise do Coágulo de Fibrina , Oclusão de Enxerto Vascular/sangue , Humanos , Masculino , Trombólise Mecânica , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/cirurgia
11.
PLoS One ; 14(1): e0209158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30650075

RESUMO

INTRODUCTION: Epoxyeicosatrienoic acids (EETs) are able to enhance angiogenesis and regulate inflammation that is especially important in wound healing under ischemic conditions. Thus, we evaluated the effect of local EET application on ischemic wounds in mice. METHODS: Ischemia was induced by cautherization of two of the three supplying vessels to the mouse ear. Wounding was performed on the ear three days later. Wounds were treated either with 11,12 or 14,15 EET and compared to untreated control and normal wounds. Epithelialization was measured every second day. VEGF, TNF-α, TGF-ß, matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), Ki67, and SDF-1α were evaluated immunohistochemically in wounds on day 3, 6, and 9. RESULTS: Ischemia delayed wound closure (12.8 days ± 1.9 standard deviation (SD) for ischemia and 8.0 days ± 0.94 SD for control). 11,12 and14,15 EET application ameliorated deteriorated wound healing on ischemic ears (7.6 ± 1.3 SD for 11,12 EET and 9.2 ± 1.4 SD for 14,15 EET). Ischemia did not change VEGF, TNF-α, TGF-ß, SDF-1α, TIMP, MMP7 or MMP9 level significantly compared to control. Local application of 11,12 as well as 14,15 EET induced a significant elevation of VEGF, TGF-ß, and SDF-1α expression as well as proliferation during the whole phase of wound healing compared to control and ischemia alone. CONCLUSION: In summary, EET improve impaired wound healing caused by ischemia as they enhance neovascularization and alter inflammatory response in wounds. Thus elevating lipid mediator level as 11,12 and 14,15 EET in wounds might be a successful strategy for amelioration of deranged wound healing under ischemia.


Assuntos
Eicosanoides/uso terapêutico , Isquemia/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Quimiocina CXCL12/sangue , Modelos Animais de Doenças , Isquemia/sangue , Metaloproteinase 7 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Camundongos , Inibidor Tecidual de Metaloproteinase-1/sangue , Fator de Crescimento Transformador beta/sangue , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/sangue
12.
Cir Cir ; 87(1): 45-52, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-30600808

RESUMO

Introduction: The purpose of this prospective cohort study was to evaluate whether serum procalcitonin (PCT) levels predict the need for surgery and the presence of ischemia and/or necrosis (I/N) in small bowel obstruction. Method: Of 54 patients included, conservative management was performed in 31 (non-surgical group) and an exploratory laparotomy in 23 (surgical group). The reference value of the PCT was between 0.10 and 0.50 ng/mL. Results: PCT levels were higher in the surgical group (7.05 ± 7.03 ng/mL) than in the non-surgical (0.37 ± 0.63 ng/mL), and in patients with I/N (10.06 ± 7.07 ng/mL) than without I/N (1.52 ± 1.45 ng/mL). In the ROC curve, the area under the curve was 0.91 for the need for surgery and 0.93 for I/N. PCT ≥ 0.80 ng/mL had the best sensitivity and specificity for surgery and ≥ 1.95 ng/mL for I/N. PCT was also an independent predictor for these events. Conclusions: The levels of PCT can recognize the need for surgery and the presence of I/N in small bowel obstruction. Additional studies are needed to affirm or invalidate our findings.


Assuntos
Obstrução Intestinal/sangue , Intestino Delgado/irrigação sanguínea , Intestino Delgado/patologia , Isquemia/sangue , Pró-Calcitonina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Obstrução Intestinal/complicações , Obstrução Intestinal/cirurgia , Intestino Delgado/cirurgia , Isquemia/cirurgia , Masculino , Pessoa de Meia-Idade , Necrose/sangue , Necrose/cirurgia , Valor Preditivo dos Testes
13.
Int J Mol Sci ; 20(1)2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30621250

RESUMO

MCP-1-induced protein (MCPIP, also known as Zc3h12a or Regnase-1), a newly identified suppressor of cytokine signaling, is expressed in endothelial cells (ECs). To investigate the role of endothelial MCPIP in vascular homeostasis and function, we deleted the MCPIP gene specifically in ECs using the Cre-LoxP system. EC-specific MCPIP deletion resulted in systemic inflammation, increased vessel permeability, edema, thrombus formation, and premature death in mice. Serum levels of cytokines, chemokines, and biomarkers of EC dysfunction were significantly elevated in these mice. Upon lipopolysaccharide (LPS) challenge, mice with EC-specific MCPIP depletion were highly susceptible to LPS-induced death. When subjected to ischemia, these mice showed defective post-ischemic angiogenesis and impaired blood flow recovery in hind limb ischemia. In aortic ring cultures, the MCPIP-deficient ECs displayed significantly impaired vessel sprouting and tube elongation. Mechanistically, silencing of MCPIP by small interfering RNAs in cultured ECs enhanced NF-κΒ activity and dysregulated synthesis of microRNAs linked with elevated cytokines and biomarkers of EC dysfunction. Collectively, these results establish that constitutive expression of MCPIP in ECs is essential to maintaining endothelial homeostasis and function by serving as a key negative feedback regulator that keeps the inflammatory signaling suppressed.


Assuntos
Células Endoteliais da Veia Umbilical Humana/metabolismo , Isquemia/metabolismo , Ribonucleases/metabolismo , Animais , Coagulação Sanguínea , Permeabilidade Capilar , Citocinas/sangue , Deleção de Genes , Humanos , Inflamação/metabolismo , Inflamação/patologia , Isquemia/sangue , Isquemia/patologia , Pulmão/patologia , Camundongos Knockout , MicroRNAs/metabolismo , Modelos Biológicos , NF-kappa B/metabolismo , Neovascularização Fisiológica , Especificidade de Órgãos , Perfusão , Fenótipo , Ribonucleases/deficiência , Trombose/sangue , Trombose/patologia , Trombose/fisiopatologia
14.
Med Clin (Barc) ; 152(1): 6-12, 2019 01 04.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29650265

RESUMO

BACKGROUND AND OBJECTIVE: In patients with peripheral artery disease requiring surgery, anaemia has been found to independently predict short and medium term higher morbidity and mortality. PATIENTS AND METHODS: We retrospectively studied all patients undergoing surgery, consecutively during 2months in 12 vascular surgery units. We analysed cardiovascular risk factors and preoperative haemoglobin. Statistical analysis was done with Kaplan-Meier for survival and logistic regression modelling to identify predictors of mortality. RESULTS: 518 patients were consecutively operated on in our vascular units, the mortality rate was 21% the first year and 34% for cardiovascular events. Preoperative anaemia was present in 63% of the ischemic patients and in 23% of the patients requiring aneurysm repair, one year after surgery it increased to 68% and 50% respectively. When preoperative anaemia was superior to 10mg/dl, one year survival increased (96% vs. 90%), fewer cardiovascular events occurred and there were fewer amputations (24% vs. 68%). CONCLUSIONS: On multivariable analysis: age, renal failure, chronic lung disease, coronary artery disease, postoperative complications and previous cardiovascular events were associated with an increased risk mortality rate. Preoperative haemoglobin influenced proportionally such that for every 1mg /dl increase, the probability of mortality decreases by 0.81. Preoperative anaemia, especially when haemoglobin is inferior to 10mg/dl, is associated with an increased risk of death and amputation.


Assuntos
Amputação/estatística & dados numéricos , Anemia/complicações , Doenças Vasculares Periféricas/cirurgia , Complicações Pós-Operatórias/mortalidade , Procedimentos Cirúrgicos Vasculares/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/epidemiologia , Aneurisma/sangue , Aneurisma/cirurgia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Causas de Morte , Feminino , Hemoglobina A/análise , Humanos , Isquemia/sangue , Isquemia/cirurgia , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/sangue , Doenças Vasculares Periféricas/mortalidade , Complicações Pós-Operatórias/sangue , Prevalência , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Procedimentos Cirúrgicos Vasculares/efeitos adversos
15.
Artigo em Inglês | MEDLINE | ID: mdl-30198519

RESUMO

AIM: The therapeutic potential of adipose-derived stem cell conditioned medium (ASC-CM) was studied in the rabbit model of critical limb ischemia (CLI). METHODS: Rabbits received treatment with ASC-CM or placebo. Gastrocnemius muscle tissue was collected 35 days after ischemia induction. Ischemic changes were evaluated in hematoxylin-eosin stained tissues for early (necrotic lesions/granulation tissue) and late (fibrous scars) phases of tissue repair. The expression of proangiogenic miR-126 was also evaluated using in situ hybridization. The levels of cytokines, insulin, and C-peptide were measured in blood. RESULTS: Early repair phases were observed more often in placebo-treated samples (45.5%) than in ASC-CM-treated ones (22.2%). However, the difference was not statistically significant. We demonstrated a statistically significant positive correlation between the early healing phases in tissue samples and C-peptide levels in peripheral blood. The expression of proangiogenic miR-126 was also shown in a number of structures in all phases of ischemic tissue healing. CONCLUSION: Based on our results, we believe that treatment with ASC-CM has the potential to accelerate the healing process in ischemic tissues in the rabbit model of CLI. The whole healing process was accompanied by miR-126 tissue expression. C-peptide could be used to monitor the course of the tissue healing process.


Assuntos
Peptídeo C/sangue , Citocinas/sangue , Diabetes Mellitus Experimental/sangue , Insulina/sangue , Isquemia/sangue , Células-Tronco Mesenquimais , Músculo Esquelético/patologia , Cicatrização/fisiologia , Adulto , Animais , Cicatriz/patologia , Meios de Cultivo Condicionados/farmacologia , Pé Diabético , Modelos Animais de Doenças , Fibrose , Tecido de Granulação/patologia , Membro Posterior , Humanos , Hibridização In Situ , Masculino , MicroRNAs/metabolismo , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/efeitos dos fármacos , Necrose , Neovascularização Fisiológica/efeitos dos fármacos , Coelhos , Cicatrização/efeitos dos fármacos
16.
Biochem Biophys Res Commun ; 508(2): 614-619, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30522866

RESUMO

Platelets play a critical role in the pathophysiology of peripheral arterial disease (PAD). The mechanisms by which muscle ischemia regulates aggregation of platelets are poorly understood. We have recently identified the Nod-like receptor nucleotide-binding domain leucine rich repeat containing protein 3 (NLRP3) expressed by platelets as a critical regulator of platelet activation and aggregation, which may be triggered by activation of toll-like receptor 4 (TLR4). In this study, we performed femoral artery ligation (FAL) in transgenic mice with platelet-specific ablation of TLR4 (TLR4 PF4) and in NLRP3 knockout (NLRP3-/-) mice. NLRP3 inflammasome activity of circulating platelets, as monitored by activation of caspase-1 and cleavage of interleukin-1ß (IL-1ß), was upregulated in mice subjected to FAL. Genetic ablation of TLR4 in platelets led to decreased platelet caspase 1 activation and platelet aggregation, which was reversed by the NLRP3 activator Nigericin. Two weeks after the induction of FAL, ischemic limb perfusion was increased in TLR4 PF4 and NLRP3-/- mice as compared to control mice. Hence, activation of platelet TLR4/NLRP3 signaling plays a critical role in upregulating platelet aggregation and interfering with perfusion recovery in muscle ischemia and may represent a therapeutic target to improve limb salvage.


Assuntos
Modelos Animais de Doenças , Membro Posterior/metabolismo , Inflamassomos/metabolismo , Isquemia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Inflamassomos/sangue , Isquemia/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/deficiência , Ativação Plaquetária , Agregação Plaquetária , Transdução de Sinais , Receptor 4 Toll-Like/sangue , Regulação para Cima
17.
Balkan Med J ; 36(2): 121-128, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30417831

RESUMO

Background: Laparoscopic partial nephrectomy, which minimizes renal function loss due to its nephron sparing nature, has become a standard technique among many experienced centers worldwide for surgical treatment of localized kidney tumors. Although partial nephrectomy will remain the gold standard, we need to improve perioperative management and surgical method to prevent postoperative acute kidney injury. Aims: To demonstrate the frequency of the development of postoperative acute kidney injury following laparoscopic partial nephrectomy in patients with healthy contralateral kidney and determine the early predictive effects of serum neutrophil gelatinase-associated lipocalin on ischemia-reperfusion injury and its association with warm ischemia time. Study Design: Cross-sectional study. Methods: Eighty patients were included. We analyzed tumor size, operating time, duration of anesthesia, and warm ischemia time. Serum samples were obtained for measurement of serum creatinine, estimated glomerular filtration rate, and neutrophil gelatinase-associated lipocalin level preoperatively, at the postoperative 2nd hour, and on postoperative days 1 and 2. We used receiver operating characteristic curve for determining the cut-off point of neutrophil gelatinase-associated lipocalin to detect postoperative acute kidney injury. Correlation analysis was performed using Spearman's test. Results: Twenty-seven patients developed acute kidney injury on postoperative day 2, and the neutrophil gelatinase-associated lipocalin level increased significantly at the postoperative 2nd hour in the acute kidney injury group (p=0.048). For a cut-off of 129.375 ng/mL neutrophil gelatinase-associated lipocalin, the test showed 70.0% sensitivity and 68.3% specificity for the detection of acute kidney injury at the postoperative 2nd hour. For a cut-off of 184.300 ng/mL neutrophil gelatinase-associated lipocalin, the test exhibited 73.3% sensitivity and 63.3% specificity for the detection of acute kidney injury on postoperative day 1. A significant correlation was found between warm ischemia time and neutrophil gelatinase-associated lipocalin level at the postoperative 2nd hour (r=0.398, p=0.003). The creatinine values were significantly higher and the estimated glomerular filtration rates were significantly lower on postoperative days 1 and 2 in the acute kidney injury group compared with those in the non-acute kidney injury group (p<0.001). Conclusion: The neutrophil gelatinase-associated lipocalin may be used as an alternative biomarker to serum creatinine in differentiation of ischemic damage in patients undergoing laparoscopic partial nephrectomy.


Assuntos
Isquemia/sangue , Lipocalina-2/análise , Nefrectomia/efeitos adversos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/etiologia , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Rim/lesões , Rim/cirurgia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Lipocalina-2/sangue , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Complicações Pós-Operatórias/sangue , Fatores de Tempo
18.
Biochimie ; 159: 107-111, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30447282

RESUMO

Intestinal ischemia, also called mesenteric ischemia, is a severe gastrointestinal and vascular medical emergency caused by a sudden decrease of blood flow through the mesenteric vessels. It generates hypoperfusion of intestinal tissues and can rapidly progress to intestinal wall infarction, systemic inflammation or even death if not treated in time. The mortality of this condition is still considerably high despite all the medical advances of the past few years. This is partially due to the difficulty of diagnosing early stage mesenteric ischemia. Indeed, a speedy and correct diagnosis is decisive for suitable medical care. However, early symptoms are unspecific and conventional clinical markers are neither specific nor sensitive enough. In the last few years, significant clinical and preclinical efforts have been made to find biomarkers which could predict gastrointestinal damage before it becomes irreversible. Here, the gut-derived hormone glucagon-like peptide-1 (GLP-1) is described as a potential early biomarker of this severe condition. Indeed, GLP-1 plasma levels rise rapidly in both mice and humans with intestinal ischemia. This discovery could counter the cruel lack of clinical biomarkers available to diagnose and therefore manage intestinal ischemia efficiently in the early stages. GLP-1 could thus become part of a panel of biomarkers for intestinal ischemia and could help to reduce the associated high mortality rates.


Assuntos
Peptídeo 1 Semelhante ao Glucagon/sangue , Enteropatias/sangue , Enteropatias/diagnóstico , Intestinos/irrigação sanguínea , Isquemia/sangue , Isquemia/diagnóstico , Animais , Biomarcadores/sangue , Humanos , Enteropatias/mortalidade , Isquemia/mortalidade
19.
Biomed Res Int ; 2018: 4232794, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30539011

RESUMO

Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease, which is common but rarely diagnosed. Noninvasive biomarkers are urgently required to assist in the diagnosis of CLI. Accumulating evidence indicates that miRNAs play an important role in the development of various diseases. In this study, microarray profiling revealed 11 miRNAs with significantly altered expression in four T2DM patients with CLI compared with that in four sex- and age-matched T2DM patients without CLI. In independent cohorts, qRT-PCR validation confirmed the increased miRNA-4739 level in patients with CLI versus patients without CLI. miRNA-4739 levels increased with FPG and HbA1c (all P < 0.05). After adjusting for the risk factors, miRNA-4739 levels were found to be associated with an increased odds ratio (OR) of T2DM with CLI (OR =12.818, 95% confidence intervals (CI) 1.148 to 143.143, P = 0.038). ROC curve analysis revealed that the area under the curve (AUC) of miR-4739+confounding risk factors was 0.94 (95% CI 0.891 to 0.998, P < 0.001), which was higher than that of confounding risk factors (AUC 0.94 vs. 0.91, 95% CI -0.122 to 0.060, P > 0.05) and of miR-4739 (AUC 0.94 vs. 0.69, 95% CI -0.399 to -0.101, P < 0.001), respectively. We conclude that elevated plasma miRNA-4739 levels are independently associated with CLI in T2DM patients. miRNA-4739 is implicated as a novel diagnostic marker and a potential therapeutic target for CLI in diabetes.


Assuntos
MicroRNA Circulante/metabolismo , Diabetes Mellitus Tipo 2/complicações , Pé Diabético/diagnóstico , Pé/irrigação sanguínea , MicroRNAs/sangue , MicroRNAs/genética , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , MicroRNA Circulante/sangue , Diabetes Mellitus Tipo 2/sangue , Pé Diabético/sangue , Feminino , Perfilação da Expressão Gênica , Humanos , Isquemia/sangue , Isquemia/diagnóstico , Isquemia/genética , Modelos Logísticos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Fatores de Risco
20.
Proc Natl Acad Sci U S A ; 115(47): E11015-E11024, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30404911

RESUMO

Transmission-mode pulse oximetry, the optical method for determining oxygen saturation in blood, is limited to only tissues that can be transilluminated, such as the earlobes and the fingers. The existing sensor configuration provides only single-point measurements, lacking 2D oxygenation mapping capability. Here, we demonstrate a flexible and printed sensor array composed of organic light-emitting diodes and organic photodiodes, which senses reflected light from tissue to determine the oxygen saturation. We use the reflectance oximeter array beyond the conventional sensing locations. The sensor is implemented to measure oxygen saturation on the forehead with 1.1% mean error and to create 2D oxygenation maps of adult forearms under pressure-cuff-induced ischemia. In addition, we present mathematical models to determine oxygenation in the presence and absence of a pulsatile arterial blood signal. The mechanical flexibility, 2D oxygenation mapping capability, and the ability to place the sensor in various locations make the reflectance oximeter array promising for medical sensing applications such as monitoring of real-time chronic medical conditions as well as postsurgery recovery management of tissues, organs, and wounds.


Assuntos
Antebraço/irrigação sanguínea , Testa/irrigação sanguínea , Oximetria/instrumentação , Oximetria/métodos , Oxigênio/sangue , Adulto , Desenho de Equipamento , Humanos , Isquemia/sangue , Modelos Teóricos , Oxiemoglobinas/análise , Oxiemoglobinas/metabolismo
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