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1.
Immunity ; 57(1): 141-152.e5, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38091996

RESUMO

Adipose tissues (ATs) are innervated by sympathetic nerves, which drive reduction of fat mass via lipolysis and thermogenesis. Here, we report a population of immunomodulatory leptin receptor-positive (LepR+) sympathetic perineurial barrier cells (SPCs) present in mice and humans, which uniquely co-express Lepr and interleukin-33 (Il33) and ensheath AT sympathetic axon bundles. Brown ATs (BATs) of mice lacking IL-33 in SPCs (SPCΔIl33) had fewer regulatory T (Treg) cells and eosinophils, resulting in increased BAT inflammation. SPCΔIl33 mice were more susceptible to diet-induced obesity, independently of food intake. Furthermore, SPCΔIl33 mice had impaired adaptive thermogenesis and were unresponsive to leptin-induced rescue of metabolic adaptation. We therefore identify LepR+ SPCs as a source of IL-33, which orchestrate an anti-inflammatory BAT environment, preserving sympathetic-mediated thermogenesis and body weight homeostasis. LepR+IL-33+ SPCs provide a cellular link between leptin and immune regulation of body weight, unifying neuroendocrinology and immunometabolism as previously disconnected fields of obesity research.


Assuntos
Tecido Adiposo Marrom , Leptina , Animais , Humanos , Camundongos , Tecido Adiposo Marrom/inervação , Tecido Adiposo Marrom/metabolismo , Peso Corporal , Metabolismo Energético/fisiologia , Interleucina-33/genética , Interleucina-33/metabolismo , Obesidade/metabolismo , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Termogênese/fisiologia
2.
J Headache Pain ; 23(1): 107, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35986251

RESUMO

BACKGROUND: Unlike the spontaneously appearing aura in migraineurs, experimentally, cortical spreading depression (CSD), the neurophysiological correlate of aura is induced by non-physiological stimuli. Consequently, neural mechanisms involved in spontaneous CSD generation, which may provide insight into how migraine starts in an otherwise healthy brain, remain largely unclear. We hypothesized that CSD can be physiologically induced by sensory stimulation in primed mouse brain. METHODS: Cortex was made susceptible to CSD with partial inhibition of Na+/K+-ATPase by epidural application of a low concentration of Na+/K+-ATPase blocker ouabain, allowing longer than 30-min intervals between CSDs or by knocking-down α2 subunit of Na+/K+-ATPase, which is crucial for K+ and glutamate re-uptake, with shRNA. Stimulation-triggered CSDs and extracellular K+ changes were monitored in vivo electrophysiologically and a K+-sensitive fluoroprobe (IPG-4), respectively. RESULTS: After priming with ouabain, photic stimulation significantly increased the CSD incidence compared with non-stimulated animals (44.0 vs. 4.9%, p < 0.001). Whisker stimulation also significantly increased the CSD incidence, albeit less effectively (14.9 vs. 2.4%, p = 0.02). Knocking-down Na+/K+-ATPase (50% decrease in mRNA) lowered the CSD threshold in all mice tested with KCl but triggered CSDs in 14.3% and 16.7% of mice with photic and whisker stimulation, respectively. Confirming Na+/K+-ATPase hypofunction, extracellular K+ significantly rose during sensory stimulation after ouabain or shRNA treatment unlike controls. In line with the higher CSD susceptibility observed, K+ rise was more prominent after ouabain. To gain insight to preventive mechanisms reducing the probability of stimulus-evoked CSDs, we applied an A1-receptor antagonist (DPCPX) to the occipital cortex, because adenosine formed during stimulation from ATP can reduce CSD susceptibility. DPCPX induced spontaneous CSDs but only small-DC shifts along with suppression of EEG spikes during photic stimulation, suggesting that the inhibition co-activated with sensory stimulation could limit CSD ignition when K+ uptake was not sufficiently suppressed as with ouabain. CONCLUSIONS: Normal brain is well protected against CSD generation. For CSD to be ignited under physiological conditions, priming and predisposing factors are required as seen in migraine patients. Intense sensory stimulation has potential to trigger CSD when co-existing conditions bring extracellular K+ and glutamate concentrations over CSD-ignition threshold and stimulation-evoked inhibitory mechanisms are overcome.


Assuntos
Depressão Alastrante da Atividade Elétrica Cortical , Transtornos de Enxaqueca , Enxaqueca com Aura , Adenosina Trifosfatases/farmacologia , Animais , Encéfalo , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Ácido Glutâmico , Camundongos , Ouabaína/farmacologia , RNA Interferente Pequeno/farmacologia
3.
Anatol J Cardiol ; 26(4): 249-257, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35435835

RESUMO

Thrombotic coronary artery occlusions usually manifest as acute coronary syndrome with cardiogenic shock, acute pulmonary edema, cardiac arrest, fatal arrhythmias, or sudden cardiac death. Although it usually occurs based on atherosclerosis, it can also occur without atherosclerosis. There is no predictor of coronary artery thrombosis clinically and no consensus regarding the optimal treatment. In the current literature, treatment options include emergency coronary artery bypass grafting, entrapment of thrombus in vessel wall with stent implantation, intracoronary thrombolysis, glycoprotein IIb/IIIa inhibitors, anticoagulation with heparin, and thrombus aspiration as reperfusion strategies. Here, we reviewed a new treatment strategy based on the literature, and a case series with successful results in hemodynamically stable patients with low-dose slow infusion tissue plasminogen activator (tPA) for thrombotic coronary artery occlusions that allow coronary flow was reported. Prospective randomized studies and common consensus are needed on low-dose, slow-infusion tissue plasminogen activator treatment regimen and optimal treatment management for thrombotic coronary artery occlusions.


Assuntos
Aterosclerose , Oclusão Coronária , Trombose Coronária , Aterosclerose/tratamento farmacológico , Trombose Coronária/terapia , Vasos Coronários , Humanos , Estudos Prospectivos , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico
4.
Neurobiol Dis ; 156: 105424, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34118418

RESUMO

Neuroinflammatory changes involving neuronal HMGB1 release and astrocytic NF-κB nuclear translocation occur following cortical spreading depolarization (CSD) in wildtype (WT) mice but it is unknown to what extent this occurs in the migraine brain. We therefore investigated in familial hemiplegic migraine type 1 (FHM1) knock-in mice, which express an intrinsic hyperexcitability phenotype, the extent of neuroinflammation without and after CSD. CSD was evoked in one hemisphere by pinprick (single CSD) or topical KCl application (multiple CSDs). Neuroinflammatory (HMGB1, NF-κB) and neuronal activation (pERK) markers were investigated by immunohistochemistry in the brains of WT and FHM1 mutant mice without and after CSD. Effects of NMDA receptor antagonism on basal and CSD-induced neuroinflammatory changes were examined by, respectively, systemically administered MK801 and ifenprodil or topical MK801 application. In FHM1 mutant mice, CSD caused enhanced neuronal HMGB1 release and astrocytic NF-κB nuclear translocation in the cortex and subcortical areas that were equally high in both hemispheres. In WT mice such effects were only pronounced in the hemisphere in which CSD was induced. Neuroinflammatory responses were associated with pERK expression indicating neuronal activation. Upon CSD, contralateral cortical and striatal HMGB1 release was reduced by topical application of MK801 in the hemisphere contralateral to the one in which CSD was induced. This study reveals that neuroinflammatory activation after CSD is widespread and extends to the contralateral hemisphere, particularly in brains of FHM1 mutant mice. Effective blockade of CSD-induced neuroinflammatory responses in the contralateral hemisphere in FHM1 mice by local NMDA receptor antagonism suggests that neuronal hyperexcitability-related neuroinflammation is relevant in migraine pathophysiology, but possibly also other neurological disorders in which spreading depolarization is involved.


Assuntos
Encéfalo/metabolismo , Ataxia Cerebelar/metabolismo , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Proteína HMGB1/metabolismo , Transtornos de Enxaqueca/metabolismo , NF-kappa B/metabolismo , Tecido Parenquimatoso/metabolismo , Animais , Astrócitos/metabolismo , Encéfalo/fisiopatologia , Ataxia Cerebelar/genética , Ataxia Cerebelar/fisiopatologia , Feminino , Proteína HMGB1/genética , Humanos , Camundongos , Camundongos Transgênicos , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/fisiopatologia , NF-kappa B/genética , Tecido Parenquimatoso/fisiopatologia
5.
Exp Neurol ; 332: 113392, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32610106

RESUMO

Although it has been documented that central nervous system pericytes are able to contract in response to physiological, pharmacological or pathological stimuli, the underlying mechanism of pericyte contractility is incompletely understood especially in downstream pericytes that express low amounts of alpha-smooth muscle actin (α-SMA). To study whether pericyte contraction involves F-actin polymerization as in vascular smooth muscle cells, we increased retinal microvascular pericyte tonus by intravitreal injection of a vasoconstrictive agent, noradrenaline (NA). The contralateral eye of each mouse was used for vehicle injection. The retinas were rapidly extracted and fixed within 2 min after injections. Polymeric/filamentous (F-actin) and monomeric/globular (G-actin) forms of actin were labeled by fluorescently-conjugated phalloidin and deoxyribonuclease-I, respectively. We studied 108 and 83 pericytes from 6 NA- and 6 vehicle-treated retinas and, found that F/G-actin ratio, a microscopy-based index of F-actin polymerization, significantly increased in NA-treated retinas [median (IQR): 4.2 (3.1) vs. 3.5 (2.1), p = .006], suggesting a role for F-actin polymerization in pericyte contractility. Shift from G-actin monomers to polymerized F-actin was more pronounced in 5th and 6th order contracted pericytes compared to non-contracted ones [7.6 (4.7) vs. 3.2 (1.2), p < .001], possibly due to their dependence on de novo F-actin polymerization for contractile force generation because they express α-SMA in low quantities. Capillaries showing F-actin polymerization had significantly reduced diameters compared to the ones that did not exhibit increased F/G-actin ratio in pericytes [near soma / branch origin diameter; 0.67 (0.14) vs. 0.81 (0.34), p = .005]. NA-responsive capillaries generally did not show nodal constrictions but a tide-like diameter decrease, reaching a maximum near pericyte soma. These findings suggest that pericytes on high order downstream capillaries have F-actin-mediated contractile capability, which may contribute to the vascular resistance and blood flow regulation in capillary bed.


Assuntos
Actinas/metabolismo , Actinas/fisiologia , Pericitos/fisiologia , Vasos Retinianos/fisiologia , Animais , Capilares/fisiologia , Feminino , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Norepinefrina/farmacologia , Polimerização , Vasoconstritores/farmacologia
6.
Acta Neuropathol Commun ; 7(1): 134, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429795

RESUMO

Increasing evidence indicates that pericytes are vulnerable cells, playing pathophysiological roles in various neurodegenerative processes. Microvascular pericytes contract during cerebral and coronary ischemia and do not relax after re-opening of the occluded artery, causing incomplete reperfusion. However, the cellular mechanisms underlying ischemia-induced pericyte contraction, its delayed emergence, and whether it is pharmacologically reversible are unclear. Here, we investigate i) whether ischemia-induced pericyte contractions are mediated by alpha-smooth muscle actin (α-SMA), ii) the sources of calcium rise in ischemic pericytes, and iii) if peri-microvascular glycogen can support pericyte metabolism during ischemia. Thus, we examined pericyte contractility in response to retinal ischemia both in vivo, using adaptive optics scanning light ophthalmoscopy and, ex vivo, using an unbiased stereological approach. We found that microvascular constrictions were associated with increased calcium in pericytes as detected by a genetically encoded calcium indicator (NG2-GCaMP6) or a fluoroprobe (Fluo-4). Knocking down α-SMA expression with RNA interference or fixing F-actin with phalloidin or calcium antagonist amlodipine prevented constrictions, suggesting that constrictions resulted from calcium- and α-SMA-mediated pericyte contractions. Carbenoxolone or a Cx43-selective peptide blocker also reduced calcium rise, consistent with involvement of gap junction-mediated mechanisms in addition to voltage-gated calcium channels. Pericyte calcium increase and capillary constrictions became significant after 1 h of ischemia and were coincident with depletion of peri-microvascular glycogen, suggesting that glucose derived from glycogen granules could support pericyte metabolism and delay ischemia-induced microvascular dysfunction. Indeed, capillary constrictions emerged earlier when glycogen breakdown was pharmacologically inhibited. Constrictions persisted despite recanalization but were reversible with pericyte-relaxant adenosine administered during recanalization. Our study demonstrates that retinal ischemia, a common cause of blindness, induces α-SMA- and calcium-mediated persistent pericyte contraction, which can be delayed by glucose driven from peri-microvascular glycogen. These findings clarify the contractile nature of capillary pericytes and identify a novel metabolic collaboration between peri-microvascular end-feet and pericytes.


Assuntos
Actinas/metabolismo , Capilares/metabolismo , Glicogênio/deficiência , Isquemia/diagnóstico por imagem , Pericitos/metabolismo , Vasos Retinianos/metabolismo , Vasoconstrição/fisiologia , Actinas/antagonistas & inibidores , Actinas/genética , Animais , Capilares/diagnóstico por imagem , Isquemia/metabolismo , Camundongos , Camundongos Transgênicos , Oftalmoscopia/métodos , Pericitos/patologia , Retina/diagnóstico por imagem , Retina/metabolismo , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/metabolismo , Vasos Retinianos/diagnóstico por imagem
7.
Anatol J Cardiol ; 21(5): 272-280, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31062761

RESUMO

The corner stone of atrial fibrillation therapy includes the prevention of stroke with less adverse effects. The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) study provided data to compare treatment strategies in Turkey with other populations and every-day practice of stroke prevention management with complications. METHODS: GARFIELD-AF is a large-scale registry that enrolled 52,014 patients in five sequential cohorts at >1,000 centers in 35 countries.This study initiated to track the evolution of global anticoagulation practice, and to study the impact of NOAC therapy in AF. 756 patients from 17 enrolling sites in Turkey were in cohort 4 and 5.Treatment strategies at diagnosis initiated by CHA2DS2-VASc score, baseline characteristics of patients, treatment according to stroke and bleeding risk profiles, INR values were analyzed in cohorts.Also event rates during the first year follow up were evaluated. RESULTS: AF patients in Turkey were mostly seen in young women.Stroke risk according to the CHADS2 score and CHA2DS2-VASc score compared with world data. The mean of risk score values including HAS-BLED score were lower in Turkey than world data.The percentage of patients receiving FXa inhibitor with or without an antiplatelet usage was more than the other drug groups. All-cause mortality was higher in Turkey. Different form world data when HAS-BLED score was above 3, the therapy was mostly changed to antiplatelet drugs in Turkey. CONCLUSION: The data of GARFIELD-AF provide data from Turkey about therapeutic strategies, best practices also deficiencies in available treatment options, patient care and clinical outcomes of patients with AF.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral/epidemiologia , Fatores Etários , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Estudos de Coortes , Feminino , Saúde Global , Humanos , Incidência , Masculino , Padrões de Prática Médica , Estudos Prospectivos , Sistema de Registros , Fatores Sexuais , Acidente Vascular Cerebral/prevenção & controle , Turquia/epidemiologia
8.
J Cardiovasc Imaging ; 27(2): 137-146, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30993949

RESUMO

BACKGROUND: This study evaluated the atrial electromechanical delay (AEMD) and the left atrial (LA) mechanical functions in patients with surgical early menopause. METHODS: A total of 62 patients were included in the study: 33 patients with surgical early menopause and 29 age- and sex-matched healthy controls. The duration distance from the start of the P wave to the beginning of the A wave for the lateral mitral annulus, septal mitral annulus, and lateral tricuspid annulus was assessed by tissue Doppler echocardiography. The differences in these durations were used to calculate the inter- and intra-atrial mechanical delays. LA volumes were evaluated using the biplane area-length technique, and LA mechanical function values were measured. RESULTS: The baseline laboratory and clinical characteristics were similar between the two groups. Surgical early menopause patients displayed increased static atrial electromechanical connection (PA') times for the septal mitral annulus and lateral tricuspid annulus compared to the controls. However, the lateral mitral annulus, the inter-atrial, the intra-LA, and the right atrial EMD PA' times were not significantly altered in surgical early menopause patients compared to controls. Importantly, the LA volume index (28.1 ± 8.17 vs. 24.89 ± 7.96 mL/m², p = 0.019), the maximal LA volume (49.6 ± 14.1 vs. 42.9 ± 16.1 mL, p = 0.004), the minimal LA volume (18.4 ± 7.0 vs. 15.2 ± 9.0 mL, p = 0.022), and the atrial precontraction LA volume (31.0 ± 10.9 vs. 24.9 ± 10.1 mL, p = 0.006) were higher in the patients with surgical early menopause compared to the controls. The LA reservoir, conduit and pumping functions and the total, passive, and active emptying volumes were all comparable between the two groups (p = 0.09; 0.06; 0.68; 0.06; 0.48; 0.07, respectively). CONCLUSIONS: Patients with surgical early menopause demonstrated impaired atrial electrical delay and electromechanical functions.

9.
Elife ; 72018 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-29561727

RESUMO

Recent evidence suggests that capillary pericytes are contractile and play a crucial role in the regulation of microcirculation. However, failure to detect components of the contractile apparatus in capillary pericytes, most notably α-smooth muscle actin (α-SMA), has questioned these findings. Using strategies that allow rapid filamentous-actin (F-actin) fixation (i.e. snap freeze fixation with methanol at -20°C) or prevent F-actin depolymerization (i.e. with F-actin stabilizing agents), we demonstrate that pericytes on mouse retinal capillaries, including those in intermediate and deeper plexus, express α-SMA. Junctional pericytes were more frequently α-SMA-positive relative to pericytes on linear capillary segments. Intravitreal administration of short interfering RNA (α-SMA-siRNA) suppressed α-SMA expression preferentially in high order branch capillary pericytes, confirming the existence of a smaller pool of α-SMA in distal capillary pericytes that is quickly lost by depolymerization. We conclude that capillary pericytes do express α-SMA, which rapidly depolymerizes during tissue fixation thus evading detection by immunolabeling.


Assuntos
Actinas/metabolismo , Capilares/metabolismo , Pericitos/metabolismo , Vasos Retinianos/metabolismo , Actinas/genética , Animais , Capilares/citologia , Imuno-Histoquímica , Camundongos Transgênicos , Músculo Liso/metabolismo , Polimerização , Interferência de RNA
10.
Arch Med Sci ; 12(1): 95-100, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26925123

RESUMO

INTRODUCTION: Neutrophil-to-lymphocyte ratio (NLR), which is an essential marker of inflammation, has been shown to be associated with adverse outcomes in various cardiovascular diseases in the literature. In this study we sought to evaluate the association between NLR and prognosis of acute pulmonary embolism (APE). MATERIAL AND METHODS: We retrospectively evaluated blood counts and clinical data of 142 patients with the diagnosis of pulmonary embolism (PE) from Ondokuz Mayis University Hospital between January 2006 and December 2012. The patients were divided into two groups according to NLR: NLR < 4.4 (low NLR group, n = 71) and NLR ≥ 4.4 (high NLR group, n = 71). RESULTS: Massive embolism (66.2% vs. 36.6%, p < 0.001) and in-hospital mortality (21.1%, 1.4%, p < 0.001) were higher in the high NLR group. In multivariate regression analysis NLR ≥ 5.7, systolic blood pressure (BP) < 90 mm Hg, serum glucose > 126 mg/dl, heart rate > 110 beats/min, and PCO2 < 35 or > 50 mm Hg were predictors of in-hospital mortality. The optimal NLR cutoff value was 5.7 for mortality in receiver operating characteristic (ROC) analysis. Having an NLR value above 5.7 was found to be associated with a 10.8 times higher mortality rate than an NLR value below 5.7. CONCLUSIONS: In patients presenting with APE, NLR value is an independent predictor of in-hospital mortality and may be used for clinical risk classification.

11.
Rev Port Cardiol ; 34(7-8): 465-71, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26164277

RESUMO

OBJECTIVE: Inflammatory mechanisms are known to play an important role in coronary artery disease. The present study aimed to investigate the importance of the neutrophil-to-lymphocyte ratio (NLR) in terms of in-hospital mortality and its association with currently used risk scores in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Three hundred and seventeen patients with NSTE-ACS were included. The patients were divided into tertiles according to their NLR values (NLR <2.6, NLR=2.6-4.5, and NLR >4.5). Clinical and angiographic risk was evaluated by the SYNTAX and GRACE risk scores. RESULTS: The GRACE risk score was significantly higher in the group with high NLR values compared to those with moderate or low NLR (161.5±40.3, 130.5±32.3, and 123.9±34.3, respectively, p<0.001). Similarly, the SYNTAX score was significantly higher in the group with high NLR values (20.4±10.1, 15.5±10.5, and 13.4±7.8, respectively, p=0.003). Moreover, both GRACE (r=0.457, p<0.001) and SYNTAX scores (r=0.253, p=0.001) showed a significant positive correlation with NLR. CONCLUSION: NLR has been found to be correlated with clinical and angiographic risk scores. Low NLR might be a good predictor for low in-hospital mortality and simple coronary anatomy in NSTE-ACS patients.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/mortalidade , Linfócitos , Neutrófilos , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco
12.
Anatol J Cardiol ; 15(6): 450-5, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25430410

RESUMO

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) is a novel inflammatory marker that is released from neutrophils. In this study, we evaluated the correlation between serum NGAL level and clinical and angiographic risk scores in patients diagnosed with non-ST elevation acute coronary syndrome (NSTE-ACS). METHODS: Forty-seven random NSTE-ACS patients and 45 patients with normal coronary arteries (NCA) who underwent coronary angiography were enrolled in the study. GRACE risk score and SYNTAX and Gensini risk scores were used, respectively, for the purpose of clinical risk assessment and angiographic risk scoring. Serum NGAL level was measured via ELISA in peripheral blood samples obtained from the patients at the time of admission. RESULTS: Serum NGAL level was significantly higher in the NSTE-ACS group compared to the control group (112.3±49.6 ng/mL vs. 58.1±24.3 ng/mL, p<0.001). There was a significant positive correlation between serum NGAL levels and the GRACE (r=0.533 and p<0.001), SYNTAX (r=0.395 and p=0.006), and Gensini risk scores (r=0.575 and p<0.001). The intermediate-high SYNTAX (>22) group had statistically significantly higher serum NGAL levels compared to the low SYNTAX (≤22) group (143±29.5 ng/mL vs. 98.7±43.2 ng/mL, p=0.001). CONCLUSION: NGAL level was positively correlated with lesion complexity and severity of coronary artery disease in patients with NSTE-ACS. Serum NGAL levels on admission are associated with increased burden of atherosclerosis in patients with NSTE-ACS.


Assuntos
Síndrome Coronariana Aguda/sangue , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Lipocalinas/sangue , Proteínas Proto-Oncogênicas/sangue , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/patologia , Proteínas de Fase Aguda , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Lipocalina-2 , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de Doença
13.
Anatol J Cardiol ; 15(6): 475-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25430414

RESUMO

OBJECTIVE: The underlying mechanism of coronary slow flow (CSF) has not yet been clarified, although many studies have been conducted to understand its pathophysiology. In this study, we investigated the role of a very potent vasoconstrictor, urotensin-II (UII), in the pathophysiology of CSF. This prospective and controlled investigation aimed to evaluate the association between CSF and serum levels of UII. METHODS: Our study included 32 patients with slow flow in any coronary artery and 32 patients with normal coronary arteries. Coronary flow was calculated using the Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) method, and CSF was defined as TFC ≥39 for the left anterior descending artery, TFC ≥27 for the circumflex coronary artery, and TFC ≥24 for the right coronary artery. UII levels in blood samples obtained from both groups were measured by enzyme-linked immunosorbent assay (ELISA) method. RESULTS: UII levels were significantly higher in the CSF group than in the control group [122 pg/mL (71-831), 95 pg/mL (21-635), respectively; p<0.001]. High-density lipoprotein (HDL) levels were lower in the CSF group, and leukocyte counts were significantly higher. A positive correlation between UII and mean TFC (r=0.524, p=0.002) was found in the CSF group. The multivariate logistic regression analysis determined that UII, HDL, and cigarette smoking were independent indicators in predicting CSF (OR=1.010, 95% confidence interval 1.002-1014, p=0.019; OR=0.927, 95% confidence interval 0.869-0.988, p=0.019; OR=5.755, 95% confidence interval 1.272-26.041, p=0.021, respectively). CONCLUSION: Serum UII levels were found to be significantly higher in the CSF group, suggesting that UII may be one of the underlying factors in the pathogenesis of CSF.


Assuntos
Biomarcadores/sangue , Circulação Coronária , Vasos Coronários , Isquemia Miocárdica/sangue , Urotensinas/sangue , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Estudos Prospectivos , Radiografia
14.
PLoS One ; 9(9): e107905, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25229454

RESUMO

Cancer-testis (CT) genes are expressed in various cancers but not in normal tissues other than in cells of the germline. Although DNA demethylation of promoter-proximal CpGs of CT genes is linked to their expression in cancer, the mechanisms leading to demethylation are unknown. To elucidate such mechanisms we chose to study the Caco-2 colorectal cancer cell line during the course of its spontaneous differentiation in vitro, as we found CT genes, in particular PAGE2, -2B and SPANX-B, to be up-regulated during this process. Differentiation of these cells resulted in a mesenchymal-to-epithelial transition (MET) as evidenced by the gain of epithelial markers CDX2, Claudin-4 and E-cadherin, and a concomitant loss of mesenchymal markers Vimentin, Fibronectin-1 and Transgelin. PAGE2 and SPAN-X up-regulation was accompanied by an increase in Ten-eleven translocation-2 (TET2) expression and cytosine 5-hydroxymethylation as well as the disassociation of heterochromatin protein 1 and the polycomb repressive complex 2 protein EZH2 from promoter-proximal regions of these genes. Reversal of differentiation resulted in down-regulation of PAGE2, -2B and SPANX-B, and induction of epithelial-to-mesenchymal transition (EMT) markers, demonstrating the dynamic nature of CT gene regulation in this model.


Assuntos
Antígenos de Neoplasias/genética , Transdiferenciação Celular/genética , Epigênese Genética , Proteínas Nucleares/genética , Diferenciação Celular/genética , Linhagem Celular Tumoral , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/metabolismo , Dioxigenases , Proteína Potenciadora do Homólogo 2 de Zeste , Transição Epitelial-Mesenquimal/genética , Humanos , Complexo Repressor Polycomb 2/metabolismo , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas/metabolismo
15.
Pak J Med Sci ; 30(5): 936-41, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25225502

RESUMO

BACKGROUND AND OBJECTIVE: The coronary slow flow phenomenon (CSFP) is a coronary artery disease with a benign course, but its pathological mechanisms are not yet fully understood.The purpose of this controlled study was to investigate the cellular content of blood in patients diagnosed with CSFP and the relationship of this with coronary flow rates. METHODS: Selective coronary angiographies of 3368 patients were analyzed to assess Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) values. Seventy eight of them had CSFP, and their demographic and laboratory findings were compared with 61 patients with normal coronary flow. RESULTS: Patients' demographic characteristics were similar in both groups. Mean corrected TFC (cTFC) values were significantly elevated in CSFP patients (p<0.001). Furthermore, hematocrit and hemoglobin values, and eosinophil and basophil counts of the CSFP patients were significantly elevated compared to the values obtained in the control group (p=0.005, p=0.047, p=0.001 and p=0.002, respectively). The increase observed in hematocrit and eosinophil levels showed significant correlations with increased TFC values (r=0.288 and r=0.217, respectively). CONCLUSION: Significant changes have been observed in the cellular composition of blood in patients diagnosed with CSFP as compared to the patients with normal coronary blood flow. The increases in hematocrit levels and in the eosinophil and basophil counts may have direct or indirect effects on the rate of coronary blood flow.

16.
Med Princ Pract ; 23(4): 336-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24924735

RESUMO

OBJECTIVE: To analyze the coronary angiograms of patients with symptomatic heart disease in order to determine the frequency and characteristics of coronary-cameral communications (CCCs) in a single center. SUBJECTS AND METHODS: The coronary angiograms of 16,573 patients with symptomatic heart disease performed from November 2001 to January 2011 were analyzed. The diagnosis of coronary fistula and coronary-cameral microcommunications (CCMCs) was made according to previously defined criteria. RESULTS: Of the 16,573 patients, 15 (0.09%; 8 males and 7 females, mean age 63 ± 12 years) had CCCs, while coronary fistulas were identified in 2 (0.01%). In the first patient, the coronary fistula arose from the branches of the left anterior descending (LAD) artery and the right coronary artery (RCA) and drained into the right ventricle. In the second patient, the fistula originated from branches of the LAD artery, the circumflex (Cx) artery and the RCA and drained into the left ventricle. In 7 patients, the CCMCs originated from the LAD artery. In 3 patients, the Cx artery was the origin. The CCMCs originated from the RCA in 2 patients. In 1 patient the CCMC took its origin from the RCA and the Cx artery, while in 2 patients the CCMCs were associated with intracardiac masses in the left atrium and the right atrium, respectively. CONCLUSION: The prevalence of CCCs in adult patients was low and that of large coronary fistulas was even lower; coronary fistulas are probably very rare in adult patients because the majority of them are detected and treated during childhood.


Assuntos
Fístula Artério-Arterial/diagnóstico , Fístula Artério-Arterial/epidemiologia , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Idoso , Fístula Artério-Arterial/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
17.
Int J Cardiovasc Imaging ; 30(6): 1057-64, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24839086

RESUMO

The myocardial performance index (MPI) reflects both the systolic and diastolic function of the heart, and is easily applied in practice. In this study, we aimed to determine the relationship between MPI and invasive haemodynamic parameters in heart failure patients. A total of 126 patients with heart failure were selected, all of whom were referred for diagnostic cardiac catheterisation, and were divided into two groups. Group I consisted of 59 patients (32 men and 27 women, mean age 61 ± 10; functional capacity New York Heart Association (NYHA) Class I; and left ventricular end-diastolic pressure (LVEDP) <16 mmHg). Group II included 67 patients (34 men and 33 women, mean age 60 ± 9; NYHA Class ≥ II; LVEDP ≥ 16 mmHg). The following parameters were measured in all patients: ejection fraction with Simpson method, the peak mitral early (E) and late (A) diastolic velocities, E/A ratio, deceleration time (DT) and tissue Doppler from four different areas of the mitral annulus (septum, lateral, inferior and anterior). In order to measure MPI with two methods (standard Doppler and tissue Doppler), isovolumetric contraction time (IVCT), isovolumetric relaxation time (IVRT) and ejection time (ET) were measured from four areas and mean values of MPI were calculated. There was no difference between the two groups in E/A ratios, DT and IVRT (p > 0.05). Group II patients had longer IVCT and ET, when compared with group I patients (p < 0.05). MPI, measured by both standard pulsed wave Doppler and tissue Doppler methods, was significantly higher in group II patients, when compared with the values obtained from group I patients (Group I: 0.50 ± 0.2 and 0.50 ± 0.14; group II: 0.98 ± 0.3 and 1.2 ± 0.32; p < 0.001). According to receiver operating characteristics curve analysis, the cut-off value for MPI measured by tissue Doppler was 0.74. The sensitivity and specificity of this value were measured as 92.5 and 91.5%, respectively. MPI measured by standard Doppler method was 0.67, and its sensitivity and specificity were 85.1 and 83.1%, respectively. We found a strong relationship between MPI and LVEDP (r = 0.83, p < 0.001; r = 0.96, p < 0.001), especially when measured by tissue Doppler. In addition, we observed a significant relationship between the MPI values measured by tissue Doppler and those measured by standard traditional methods (r = 0.85, p < 0.001). We showed that MPI was reliable for the evaluation of global cardiac functions in patients with heart failure, as measured with both pulsed-wave Doppler and tissue Doppler. We assert that, in order to differentiate between those patients with symptomatic heart failure from the asymptomatic cases, MPI as measured with the tissue Doppler method is an improvement on MPI as measured using traditional methods.


Assuntos
Ecocardiografia Doppler , Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Hemodinâmica , Contração Miocárdica , Função Ventricular Esquerda , Idoso , Área Sob a Curva , Ecocardiografia Doppler de Pulso , Feminino , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Valor Preditivo dos Testes , Curva ROC , Volume Sistólico , Fatores de Tempo , Pressão Ventricular
18.
Blood Coagul Fibrinolysis ; 25(7): 688-94, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24721807

RESUMO

The data on the successful use of oral anticoagulation (OAC) in patients with atrial fibrillation are inconclusive. We aimed to describe the indications and the utilization patterns of OAC therapy in patients with atrial fibrillation who have been admitted to a quaternary hospital. Patients who were admitted to a quaternary hospital from January 2011 to January 2012 with atrial fibrillation were included in the study. The data on patient demographics, atrial fibrillation classification, CHA2DS2VASc scores, and the use of OAC were collected. Of the patients admitted, 301 patients met the inclusion criteria. Of these, 277 (92%) had a CHA2DS2VASc score at least 2. Of the patients who met criteria for treatment with OAC, 104 (36.6%) were not on OAC therapy. The reason for this discrepancy was tendency and history of bleeding (29.8%). Of those 180 patients who were on OAC, the time in therapeutic range was higher in those patients less than 50 years as compared with those between ages 65-74 and more than 75 (78.2 versus 42 and 36.1%, P < 0.05). The overall time in therapeutic range of patients on OAC was 47.4%. We found that approximately one-third of the patients who have indications for OAC are not being treated as per guidelines due to history of and tendency for bleeding. Furthermore, of those on OAC, only half of the patients achieved successful anticoagulation.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Administração Oral , Idoso , Feminino , Humanos , Masculino , Projetos Piloto , Fatores de Risco , Resultado do Tratamento
19.
J Thorac Dis ; 5(5): 650-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24255779

RESUMO

PURPOSE: This study compared patients who underwent cardiac resynchronization therapy (CRT) by high-amplitude left ventricular (LV) pacing with those who underwent CRT by standard LV pacing. METHODS: We included 32 CRT patients with ejection fraction (EF) ≤35%, QRS time ≥120 ms, and New York Heart Association (NYHA) class III/IV symptoms of heart failure despite optimal medical treatment. These patients were evaluated clinically and echocardiographically before, three and six months after CRT. At the 3(rd) month, the LV pulse amplitude value was set high at 5 volt for 16 patients [high-amplitude Group (HAG)], while for the other 16 patients, it was reduced to at least twice the threshold value at ≤2.5 volt [low-amplitude group (LAG)]. RESULTS: Clinical and echocardiographic response rates of HAG and LAG after CRT were similar in the 3(rd) and 6(th) month. In both groups, increase in LVEF and decrease in LV ESV in the 3(rd) and 6(th) month were statistically significant compared to those before CRT, and NYHA class and end-diastolic volume (EDV) was significantly reduced in the 6(th) month compared to those before CRT. However, NHYA class and EDV continued to reduce significantly in HAG from the 3(rd) to the 6(th) month (P<0.05), while the decrease in LAG was not significant (P>0.05). The rate of mitral regurgitation (MR) was reduced significantly in HAG in the 6(th) month compared to that before CRT, while the decrease in LAG was not significant (P<0.05; P>0.05 respectively). CONCLUSIONS: CRT by high-amplitude LV pacing was more effective according to clinical and echocardiographic evaluations. It should be considered as an alternative in non-responsive patients.

20.
Exp Clin Cardiol ; 18(2): 121-3, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23940436

RESUMO

BACKGROUND/OBJECTIVES: Coronary artery anomalies are present at birth, but relatively few are symptomatic. The majority are discovered incidentally. In the present study, coronary angiograms performed in the authors' centre (Ondokuz Mayis University Hospital, Samsun, Turkey) were analyzed to determine the prevalence and types of coronary artery origin and course anomalies. METHODS: Coronary angiographic data of 16,573 patients were analyzed. Anomalous origins and courses of coronary arteries were assessed. RESULTS: Anomalous coronary arteries were detected in 48 (0.29%) of 16,573 patients. The origin of the circumflex (Cx) artery from the right coronary artery (RCA) or right sinus of Valsalva was the most common anomaly (28 patients [58.3%]). An anomalous RCA originating from the left anterior descending artery (LAD) or Cx artery was observed in six patients (12.5%). The left coronary artery originated from the right sinus of Valsalva in five patients, and the LAD originated from the RCA or the right sinus of Valsalva in five patients. The RCA originated from the left sinus of Valsalva in three patients and from an ectopic ostium in the ascending aorta in one patient. CONCLUSIONS: The most frequent anomaly observed in the present study was related to the Cx artery, which is consistent with previous reports. Although coronary artery anomalies are rare, they may cause difficulties during coronary interventions or cardiac surgery and may occasionally result in sudden cardiac death. Therefore, the recognition and diagnosis of these anomalies is important and requires specialization in coronary angiographic techniques and other imaging modalities.

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