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BACKGROUND: The literature on the systemic inflammatory reaction following tourniquet-induced ischemia and reperfusion in elective orthopedic surgery is limited. METHODS: This prospective comparative study compared the levels of clinically relevant cytokines and peripheral blood counts and major complications in patients undergoing total knee arthroplasty (TKA) with or without a tourniquet during the first postoperative day. Forty-three patients undergoing primary TKA for degenerative osteoarthritis were divided into two groups; 21 patients were operated on using (TG group) and 22 (NTG group) without using a tourniquet. Proinflammatory cytokines interleukin-1b, interleukin-6, anti-inflammatory cytokine interleukin-10, intercellular and vascular adhesion molecules, C-reactive protein, and full blood count were evaluated preoperatively and at one, three, six, and 24 hours postoperatively in both groups. RESULTS: Demographics, American Society of Anesthesiologists score, surgery duration, osteoarthritis grade, and other preoperative variable values were comparable between groups. The average tourniquet time was 67.8 minutes. The majority of testing variables did not demonstrate significant postoperative differences between groups. However, the mean IL-6 value was non-significantly higher for the TG than the NTG group during the first six postoperative hours. It demonstrated a trend to significance at the end of the first postoperative day. The mean hemoglobin and hematocrit levels were significantly higher for the NTG group at the sixth postoperative hour. CONCLUSIONS: The tourniquet use may affect the systemic inflammatory response. Patients undergoing TKA with or without a tourniquet demonstrated a similar systemic inflammatory response. However, reperfusion following approximately 70 minutes of tourniquet ischemia is a safe practice. HIPPOKRATIA 2021, 25 (1):31-37.
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OBJECTIVE: Leptin is an adipokine, known to be associated with oxidative stress, inflammation, and atherogenesis. Leptin plays an essential role in atheromatosis-associated inflammatory cascade through stimulation of inflammatory mediators such as soluble intracellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). However, little is known about this association in patients with atherosclerosis and severe internal carotid artery (ICA) stenosis undergoing carotid endarterectomy (CEA). Our objective was to evaluate the variations of serum leptin levels, as well as sICAM-1 and sVCAM-1 levels in these patients during the process of CEA and 24 hours postoperatively. PATIENTS AND METHODS: The study group enrolled 50 patients undergoing CEA for ICA stenosis (> 70%). Serum leptin, sICAM-1 and sVCAM-1 plasma concentration measurements were performed at 4 distinct time points: before clamping of the ICA, 30 minutes after clamping of the ICA, 60 minutes after declamping of ICA and 24 hours postoperatively. RESULTS: Leptin was significantly decreased during CEA, but an overshooting in its levels was observed at 24 hours after the operation. Both sICAM-1 and sVCAM-1 initially followed the pattern of leptin changes but after completing CEA and up to 24 hours postoperatively a steep increase in their levels was not established. sVCAM-1 and sICAM-1 correlated with indices of oxidative stress at peak inflammatory burden. CONCLUSIONS: Leptin is a circulating marker of carotid atherosclerosis. Oxidative stress and expression of sVCAM-1 and sICAM-1 on vascular endothelial cells are key features in the pathophysiological process of atherosclerosis.
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Estenosis Carotídea/cirugía , Endarterectomía Carotidea/métodos , Molécula 1 de Adhesión Intercelular/sangre , Leptina/sangre , Molécula 1 de Adhesión Celular Vascular/sangre , Anciano , Estenosis Carotídea/sangre , Estudios de Casos y Controles , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Estudios ProspectivosRESUMEN
Immune system is crucial to tumour's initiation, progress and establishment and is contributing to prevent upcoming damaging invasion. Tumour development and surgical resection are both immunosuppressive processes. Immune response could be evaluated by ex vivo lipopolysaccharide (LPS) test, measuring cytokines and receptors release. The aim of the study is to investigate the postoperative immune recovery of cancer patients upon discharge. Twenty-two patients with colon cancer, without pre-treatment, and 16 healthy volunteers (HV) were enrolled in the study. Ten ml of whole blood were collected from every patient on admission (PRE) and upon discharge (POD7) and every HV. Diluted whole blood samples were stimulated with 500 pg/ml LPS, at 37°C, for 4H. Cell culture supernatants (CCSP) were removed after centrifugation and stored at -70°C. Tumour necrosis factor-alpha (TNF-α), interleukin-6 and interleukin-10 (IL-6, IL-10), soluble TNF receptors (sTNFRs) were measured in serum and CCSP by enzymelinked immunosorbent assay. Serum cytokines and receptors, PRE and POD7, were significantly elevated compared to HV (P < 0.001) and significant correlations were found between POD7 IL-6 and sTNFRs (Spearman's ρ 0.47, P < 0.05). Ex vivo, TNF-α, IL-6 and TNFRI release were lower either PRE or POD7, while IL-10 and TNFRII were higher, than in HV. No significant differences (P > 0.05) were found between PRE and POD7 levels in serum or CCSP. Cancer patients are not postoperatively immune restored until discharge. The trend of anti-inflammatory TNFRs release could account for alternative marker for the control of cancer patients immune response and the schedule of their following therapeutic treatment.
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Neoplasias del Colon/inmunología , Neoplasias del Colon/patología , Receptores del Factor de Necrosis Tumoral/análisis , Células Cultivadas , Neoplasias del Colon/cirugía , Medios de Cultivo/química , Citocinas/análisis , Ensayo de Inmunoadsorción Enzimática , Humanos , Lipopolisacáridos/inmunología , Suero/químicaRESUMEN
BACKGROUND: Antitumor activity of paclitaxel is based on promotion of abnormal microtubule (MT) assembly but it is also considered to have significant pro-inflammatory and anti-angiogenic effects in vivo and thus may cause vascular dysfunction. METHODS: We studied 27 women treated with paclitaxel-containing combinations for breast or ovarian cancer. The control group was represented by 10 women with carcinoma of the uterine cervix who received low doses of weekly cisplatin as radiation sensitizer. We measured endothelial-dependent flow-mediated dilatation (FMD) and nitrate-mediated dilatation (NMD) of the right brachial artery by ultrasonography, as well as levels of the inflammatory cytokines TNF-alpha and IL-6 before and after chemotherapy. RESULTS: Patients who received paclitaxel and an anthracycline had the most marked reduction in both FMD (p=0.005) and NMD (p=0.027). A significant reduction in FMD was also observed in patients treated with weekly paclitaxel (p=0.045), whereas NMD was not affected (p=0.421). Although TNF-alpha and IL-6 levels were different among chemotherapy groups after treatment, no significant differences were observed between levels of both markers before and after chemotherapy. CONCLUSION: Treatment with paclitaxel-containing combinations impairs endothelial function in vivo but endothelial function deterioration is not related to the serum levels of inflammation markers.
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Antineoplásicos Fitogénicos/efectos adversos , Arteria Braquial/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Paclitaxel/efectos adversos , Vasodilatación/efectos de los fármacos , Adulto , Anciano , Antraciclinas/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores/sangre , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/fisiopatología , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Casos y Controles , Cisplatino/administración & dosificación , Endotelio Vascular/diagnóstico por imagen , Endotelio Vascular/fisiopatología , Femenino , Humanos , Interleucina-6/sangre , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Factor de Necrosis Tumoral alfa/sangre , UltrasonografíaRESUMEN
The purpose of the study was to investigate the effect of different ventilatory strategies on local and systemic cytokine production in swine with intact lungs in vivo after 4 h of mechanical ventilation. Twenty-five swine were anesthetized and then randomized into five groups (n = 5): (1) low tidal volume zero PEEP (LVZP); (2) medium tidal volume zero PEEP (MVZP); (3) high tidal volume zero PEEP (HVZP); (4) low tidal volume PEEP (LVP); (4) high tidal volume PEEP (HVP). Respiratory rate was adjusted to maintain normocapnia and fraction of inspired oxygen (FiO2) was 1.0. TNF-alpha and IL-10 were measured in BALF and serum at baseline, 2 h, and 4 h of MV. One animal in LVZP (2 h) and two in HVP (3 h) group died before the end of the experiment. TNF-alpha level in BALF was significantly higher in LVZP and LVP at 4 h compared to baseline and the other groups. IL-10 level in BALF was significantly higher in LVP at 4h compared to baseline and the other groups. There was a statistically significant increase in serum TNF-alpha levels at 4 h in LVP group compared to baseline and the other groups at 4 h. There was statistically significant increase in serum IL-10 levels in HVZP and LVP groups at 2 and 4 h which was significantly higher compared to the other groups at 4 h. Our results show that a) low volume MV may induce local and systemic pro- and anti-inflammatory cytokine increase b) in the presence of pro-inflammatory cytokine response there is also an anti-inflammatory response in the same compartment (lungs, circulation). c) There maybe loss of alveolar-to-systemic cytokine compartmentalization.
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Citocinas/metabolismo , Pulmón/metabolismo , Respiración Artificial , Animales , Análisis de los Gases de la Sangre , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Citocinas/análisis , Citocinas/sangre , Interleucina-10/análisis , Interleucina-10/sangre , Interleucina-10/metabolismo , Masculino , Neumonía/etiología , Respiración Artificial/efectos adversos , Respiración Artificial/métodos , Porcinos , Factores de Tiempo , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
We examined the effects of bronchoalveolar lavage (BAL) and BAL fluid characteristics on the systemic proinflammatory cytokine expression and their relation to clinical and laboratory findings. Thirty patients suspected to have lung cancer were subjected to fiber-optic bronchoscopy (FOB) and BAL. Clinical and laboratory findings were determined at baseline, 4 h, and 24 h, including lung auscultation, temperature, chest X-ray, WBC, neutrophils, and serum IL-1beta, IL-6, and TNF-alpha. BAL fluid characteristics were determined including cytokine levels. Fifteen volunteers served as controls to determine serum variation of the same cytokines. Significant temperature elevation was defined as 1 degrees C increase compared to baseline. BAL was associated with temperature and serum TNF-alpha and IL-6 but not IL-1beta increase at 4 h. Four patients (13.3%) developed temperature over 38 degrees C. In controls there were no significant changes between baseline and 24 h measurements for the same cytokines. Eleven patients (36.6%) developed a significant temperature elevation 4 h after BAL. These patients had a statistically significant ( p < 0.05) increase in serum IL-6 at 4 h and in TNF-alpha at both 4 and 24 h after BAL compared with the nonsignificant temperature increase group. BAL characteristics were not different between the two groups. On the other hand, BAL fluid IL-6 and TNF-alpha levels were significantly higher ( p < 0.05) in the nonfever group. Significant temperature increase was observed in 36.6% of the patients undergoing BAL and associated with significant serum TNF-alpha and IL-6 increase at 4 h. Lung cytokines levels, alveolar macrophages, and BAL fluid characteristics are not related to temperature and serum proinflammatory cytokine increase. The hypothesis of alveolar macrophages derive from cytokine production and shift to the systemic circulation cannot be supported by our data.
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Temperatura Corporal/fisiología , Lavado Broncoalveolar , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Citocinas/sangre , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/fisiopatología , Adenocarcinoma/sangre , Adenocarcinoma/fisiopatología , Adulto , Anciano , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Broncoscopía , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/fisiopatología , Femenino , Hemodinámica/fisiología , Humanos , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Oxígeno/sangre , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Background: Several reports have shown that circulating, soluble cellular adhesion molecules and endothelin-1 (ET-1) are implicated in the pathophysiological events of atherosclerosis and may reflect the endothelial dysfunction characterizing this disorder. Methods: To evaluate the expression of these factors in arterial hypertension (AH), we measured plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble P-selectin (sP-selectin), and ET-1 in 60 untreated patients with mild to moderate AH (hypercholesterolemic: n=31, normocholesterolemic: n=29) and 30 sex- and age-matched normocholesterolemic normotensive controls. Results: Hypertensive patients exhibited significantly higher levels of sICAM-1 (234+/-21 vs. 187+/-12 ng/ml, P<0.005), sVCAM-1 (681+/-42 vs. 589+/-23 ng/ml, P<0.005), sP-selectin (89+/-17 vs. 55+/-11 ng/ml, P<0.01) and ET-1 (6.2+/-0.7 vs. 2.4+/-0.3 pg/ml, P<0.01) than did normotensive controls. The normocholesterolemic hypertensives had lower levels of sICAM-1, sVCAM-1 (P<0.01), sP-selectin and ET-1 (P<0.05) than hypercholesterolemic hypertensives, but higher levels than normotensive controls (P<0.05). In hypertensives, plasma ET-1 was significantly correlated with mean arterial pressure (r=0.51, P<0.03) and sICAM-1 levels (r=0.64, P<0.01). In hypercholesterolemic hypertensives, LDL cholesterol was also significantly correlated with plasma levels of sICAM-1 (r=0.53, P<0.04) and sP-selectin (r=0.41, P<0.05). Conclusions: Plasma levels of soluble cellular adhesion molecules are elevated in hypertensive patients in comparison to normotensive controls and may be related to plasma ET-1 activity. The coexistence of hypercholesterolemia may enhance the plasma soluble adhesion molecule activity induced by AH.
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Cachexia is a strong predictor for mortality in patients with congestive heart failure. To investigate the role of leptin and regulators of apoptosis in cardiac cachexia we compared leptin concentrations and their relation to the TNF system, interleukin 1-beta (IL-1b), and soluble Fas in patients with heart failure with and without cachexia. Patients with cardiac cachexia have increased levels of interleukin-1b compared to non-cachectic heart failure patients [mean(S.E.)=1.11(0.62) vs. 0.02(0.02), P=0.01] and decreased concentrations of leptin [10.79(3.93) vs. 23.24 (8.35), P=0.1]. Leptin levels correlate with TNF-RI in cachectic heart failure patients (r=0.58, P=0.018). The TNF-RI levels were also correlated with Fas, both in all the patients taken together (r=0.5, P=0.006) and in those with cachexia (r=0.52, P=0.036). Our data indicate that more prospective studies are needed to clarify the role of leptin in the pathophysiology of heart failure cachexia.
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Caquexia/sangre , Insuficiencia Cardíaca/sangre , Leptina/sangre , Anciano , Caquexia/fisiopatología , Ensayo de Inmunoadsorción Enzimática , Insuficiencia Cardíaca/fisiopatología , Humanos , Interleucina-1/sangre , Masculino , Persona de Mediana Edad , Receptores de Leptina , Estadísticas no Paramétricas , Factor de Necrosis Tumoral alfa/metabolismo , Receptor fas/sangreRESUMEN
In this report, we showed for the first time that granulocyte-macrophage colony-stimulating factor plasma levels are elevated in patients with severe heart failure, and these levels are correlated well with neurohormonal activation and hemodynamic deterioration characterizing this syndrome.
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Cardiomiopatía Dilatada/complicaciones , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Insuficiencia Cardíaca/sangre , Isquemia Miocárdica/complicaciones , Biomarcadores/sangre , Cateterismo Cardíaco , Gasto Cardíaco , Cardiomiopatía Dilatada/sangre , Cardiomiopatía Dilatada/fisiopatología , Femenino , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/sangre , Isquemia Miocárdica/fisiopatología , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
There is considerable interest in identifying the basic mechanisms by which dexamethasone alters ion transport across the adult alveolar epithelium. Herein, we incubated synchronized A549 cells, a human alveolar epithelial cell line, with dexamethasone (1 microM) for 24-48 h. When normalized to HPRT (a housekeeping gene), A549 beta- and gamma-subunit mRNA levels for the human amiloride-sensitive epithelial sodium channel (hENaC), assessed by RT-PCR, increased by 1.6- and 17-fold respectively, compared with control values (P < 0.05). These changes were abolished by actinomycin D, indicating transcriptional regulation. Western blotting studies revealed that dexamethasone also increased expression of beta- and gamma-hENaC protein levels. In contrast, alpha-hENaC mRNA increased by onefold (P > 0.05) and alpha-hENaC protein level was unchanged. Incubation of A549 cells with dexamethasone increased their whole cell amiloride-sensitive sodium currents twofold and decreased the K(0.5) for amiloride from 833 +/- 69 to 22 +/- 5.4 nM (mean +/- SE; P < 0.01). Single channel recordings in the cell-attached mode showed that dexamethasone treatment increased single channel open time and open probability threefold and decreased channel conductance from 8.63 +/- 0.036 to 4. 4 +/- 0.027 pS (mean +/- SE; P < 0.01). We concluded that dexamethasone modulates the amiloride-sensitive Na(+) channels by differentially regulating the expression of beta- and gamma-subunits at the mRNA and protein levels in the human A549 cell line, with little effect on alpha-hENaC subunit.
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Antiinflamatorios/farmacología , Dexametasona/farmacología , Pulmón/metabolismo , Canales de Sodio/efectos de los fármacos , Canales de Sodio/fisiología , Administración Tópica , Línea Celular , Conductividad Eléctrica , Electrofisiología , Canales Epiteliales de Sodio , Glucocorticoides , Humanos , Pulmón/citología , Pulmón/fisiología , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Canales de Sodio/genéticaRESUMEN
OBJECTIVE: A number of different hormone changes have been described during the acute myocardial infarction (AMI), including those of the non-thyroidal illness syndrome (NTIS). DESIGN AND METHODS: We assessed the alterations of serum thyroid hormones, cytokines and cortisol levels in 30 patients with a first episode of AMI 4, 24, 48h and 10 days (240h) after the onset of the chest pain and we investigated the possible relationship of these alterations with the severity of AMI. RESULTS: Fifteen patients had left ventricular ejection fraction (LVEF) =50% (group I) and 15 patients had LVEF >50% (group II). A transient decrease of total tri-iodothyronine (T(3)), more prominent in group I (P<0.05, t-test) with a concomitant rise of reverse T(3 )(rT(3)) occurred at 24h. Total thyroxine (T(4)), free T(4) (FT(4)) and free T(4) index did not change significantly, but tended to be higher in group I patients, whereas TSH significantly increased in group II at 48h. Interleukin-6 (IL-6) increased significantly at 24h only in group I and declined thereafter (24 vs 240h, P<0.001) and this temporal change of IL-6 was associated with similar changes of creatine phosphokinase and creatine kinase isoenzyme MB (CK-MB). Tumor necrosis factor-alpha and IL-1beta remained low in both groups. Cortisol was higher at 4h and in 12 patients was above the normal values. Negative correlation was found between LVEF and IL-6 (P<0. 001), whereas T(3), T(4) or cortisol levels were not correlated with the LVEF. CONCLUSIONS: Our data indicate that NTIS, in association with increase of IL-6, occurs in the early post-infarction period. In the NTIS following AMI the high level of IL-6 is the best predictor, among several parameters, of the severity of AMI as assessed by the LVEF and the rise of CK-MB.
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Citocinas/sangre , Hidrocortisona/sangre , Infarto del Miocardio/sangre , Hormonas Tiroideas/sangre , Anciano , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Volumen Sistólico , Pruebas de Función de la Tiroides , Factores de TiempoRESUMEN
The present study investigates the differences in serum activity of granulocyte-macrophage colony-stimulating factor, macrophage chemoattractant protein-1, and macrophage inflammatory protein-1alpha between hypertensive patients with and without significant hyperlipidemia before receiving any medical treatment. The serum activity of the studied inflammatory factors is more elevated in hypertensive patients with significant hyperlipidemia and may be associated with atherosclerotic inflammatory process induced by the coexistence of 2 major cardiovascular risk factors.
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Quimiocina CCL2/sangre , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Hiperlipidemias/sangre , Hipertensión/sangre , Proteínas Inflamatorias de Macrófagos/sangre , Estudios de Casos y Controles , Quimiocina CCL4 , Femenino , Humanos , Hiperlipidemias/complicaciones , Hipertensión/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
Alveolar epithelial cells effect edema clearance by transporting Na(+) and liquid out of the air spaces. Active Na(+) transport by the basolaterally located Na(+)-K(+)-ATPase is an important contributor to lung edema clearance. Because alveoli undergo cyclic stretch in vivo, we investigated the role of cyclic stretch in the regulation of Na(+)-K(+)-ATPase activity in alveolar epithelial cells. Using the Flexercell Strain Unit, we exposed a cell line of murine lung epithelial cells (MLE-12) to cyclic stretch (30 cycles/min). After 15 min of stretch (10% mean strain), there was no change in Na(+)-K(+)-ATPase activity, as assessed by (86)Rb(+) uptake. By 30 min and after 60 min, Na(+)-K(+)-ATPase activity was significantly increased. When cells were treated with amiloride to block amiloride-sensitive Na(+) entry into cells or when cells were treated with gadolinium to block stretch-activated, nonselective cation channels, there was no stimulation of Na(+)-K(+)-ATPase activity by cyclic stretch. Conversely, cells exposed to Nystatin, which increases Na(+) entry into cells, demonstrated increased Na(+)-K(+)-ATPase activity. The changes in Na(+)-K(+)-ATPase activity were paralleled by increased Na(+)-K(+)-ATPase protein in the basolateral membrane of MLE-12 cells. Thus, in MLE-12 cells, short-term cyclic stretch stimulates Na(+)-K(+)-ATPase activity, most likely by increasing intracellular Na(+) and by recruitment of Na(+)-K(+)-ATPase subunits from intracellular pools to the basolateral membrane.
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Alveolos Pulmonares/metabolismo , Receptores de Estiramiento Pulmonares/fisiología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Adenosina Trifosfato/metabolismo , Amilorida/farmacología , Animales , Transporte Biológico , Línea Celular , Membrana Celular/metabolismo , Epitelio/metabolismo , Gadolinio/farmacología , Ratones , Nistatina/farmacología , Rubidio/metabolismo , Sodio/metabolismoRESUMEN
Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that produces left ventricular dysfunction and a negative inotropic effect in cardiac tissue when overexpressed in human subjects. Previous studies have shown that levels of circulating TNF-alpha are elevated in patients with advanced congestive heart failure (CHF) and especially in those with cardiac cachexia. To clarify the potential role of TNF-alpha in the unstable state of decompensated advanced CHF, we investigated the TNF-alpha serum activity in 25 cachectic and 22 non-cachectic CHF patients (New York Heart Association, NYHA functional classes III or IV), who were treated with intravenous diuretics and positive inotropic agents for acute decompensation of the disease, during a 5-day hospitalization period, as well as in 15 age-matched healthy control subjects. Cachectic CHF patients needed higher dosages of inotropic agents than non-cachectic patients and the determination of TNF-alpha serum concentrations in this patient group showed high levels of TNF-alpha at hospital admission (18.3 +/- 3.2 pg/ml) and a transient increase in circulating TNF-alpha during the treatment period with the highest levels on the 2nd day of hospitalization (32.5 +/- 7.1 pg/ml). The TNF-alpha serum levels were low in non-cachectic CHF patients and healthy controls on the 1st day (4.0 +/- 0.9 and 3.7 +/- 0.6 pg/ml, respectively) and did not change substantially during the course of the study. The present results show that TNF-alpha serum activity is transiently increased during the treatment of decompensated cachectic CHF patients only and may be related to the clinical instability and the consequent therapeutic interventions in this category of CHF patients.