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1.
J Neurotrauma ; 38(24): 3431-3439, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34541888

RESUMEN

Neurological examination in the acute phase after spinal cord injury (SCI) is often impossible and severely confounded by pharmacological sedation or concomitant injuries. Therefore, diagnostic biomarkers that objectively characterize severity or the presence of SCI are urgently needed to facilitate clinical decision-making. This study aimed to determine if serum markers of neural origin are related to: 1) presence and severity of SCI, and 2) magnetic resonance imaging (MRI) parameters in the very acute post-injury phase. We performed a secondary analysis of serological parameters, as well as MRI findings in patients with acute SCI (n = 38). Blood samples were collected between Days 1-4 post-injury. Serum protein levels of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and neurofilament light protein (NfL) were determined. A group of 41 age- and sex-matched healthy individuals served as control group. In the group of individuals with SCI, pre-operative sagittal and axial T2-weighted and sagittal T1-weighted MRI scans were available for 21 patients. Serum markers of neural origin are different among individuals who sustained traumatic SCI depending on injury severity, and the extent of the lesion according to MRI in the acute injury phase. Unbiased Recursive Partitioning regression with Conditional Inference Trees (URP-CTREE) produced preliminary cut-off values for NfL (75.217 pg/mL) and GFAP (73.121 pg/mL), allowing a differentiation between individuals with SCI and healthy controls within the first 4 days after SCI. Serum proteins NfL and GFAP qualify as diagnostic biomarkers for the presence and severity of SCI in the acute post-injury phase, where the reliability of clinical exams is limited.


Asunto(s)
Edema/sangre , Edema/etiología , Proteína Ácida Fibrilar de la Glía/sangre , Proteínas de Neurofilamentos/sangre , Traumatismos de la Médula Espinal/sangre , Traumatismos de la Médula Espinal/complicaciones , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosfopiruvato Hidratasa/sangre , Factores de Tiempo
2.
Int J Mol Sci ; 22(8)2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33919841

RESUMEN

Sodium restriction is often recommended in heart failure (HF) to block symptomatic edema, despite limited evidence for benefit. However, a low-sodium diet (LSD) activates the classical renin-angiotensin-aldosterone system (RAAS), which may adversely affect HF progression and mortality in patients with dilated cardiomyopathy (DCM). We performed a randomized, blinded pre-clinical trial to compare the effects of a normal (human-equivalent) sodium diet and a LSD on HF progression in a normotensive model of DCM in mice that has translational relevance to human HF. The LSD reduced HF progression by suppressing the development of pleural effusions (p < 0.01), blocking pathological increases in systemic extracellular water (p < 0.001) and prolonging median survival (15%, p < 0.01). The LSD activated the classical RAAS by increasing plasma renin activity, angiotensin II and aldosterone levels. However, the LSD also significantly up-elevated the counter-regulatory RAAS by boosting plasma angiotensin converting enzyme 2 (ACE2) and angiotensin (1-7) levels, promoting nitric oxide bioavailability and stimulating 3'-5'-cyclic guanosine monophosphate (cGMP) production. Plasma HF biomarkers associated with poor outcomes, such as B-type natriuretic peptide and neprilysin were decreased by a LSD. Cardiac systolic function, blood pressure and renal function were not affected. Although a LSD activates the classical RAAS system, we conclude that the LSD delayed HF progression and mortality in experimental DCM, in part through protective stimulation of the counter-regulatory RAAS to increase plasma ACE2 and angiotensin (1-7) levels, nitric oxide bioavailability and cGMP production.


Asunto(s)
Angiotensina I/biosíntesis , GMP Cíclico/metabolismo , Dieta Hiposódica , Edema/prevención & control , Insuficiencia Cardíaca/complicaciones , Óxido Nítrico/metabolismo , Fragmentos de Péptidos/biosíntesis , Animales , Disponibilidad Biológica , Biomarcadores/sangre , Presión Sanguínea , Cardiomiopatía Dilatada/complicaciones , Cardiomiopatía Dilatada/fisiopatología , Edema/sangre , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Riñón/fisiopatología , Masculino , Ratones Endogámicos C57BL , Péptido Natriurético Encefálico/metabolismo , Óxido Nítrico/sangre , Óxido Nítrico Sintasa/metabolismo , Hidrolasas Diéster Fosfóricas/metabolismo , Derrame Pleural , Sistema Renina-Angiotensina , Análisis de Supervivencia , Sístole
3.
J Obstet Gynaecol ; 41(1): 73-76, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32420780

RESUMEN

The exact prevalence of mirror syndrome remains unclear, and the precise clinical features need to be disclosed. We retrospectively reviewed 85 cases of foetal hydrops from a total of 98,484 deliveries. Of these 16 showed mirror syndrome, while 69 did not. The incidence of mirror syndrome among all deliveries was 0.0162%, while that among patients with foetal hydrops was 23.2%. Maternal symptoms of mirror syndrome included anaemia (n = 15), hypertension (n = 7), proteinuria (n = 8), pulmonary oedema (n = 3), cardiac failure (n = 2) and HELLP syndrome (n = 2). Placental thickness, placental weight and amniotic fluid index were significantly different between the groups. In the mirror syndrome group, uric acid, lactate dehydrogenase, creatinine and D-dimer levels were significantly higher (p < .05), whereas haemoglobin, serum albumin levels, haematocrit value and platelet count were significantly lower (p < .05). Elevated uric acid, lactate dehydrogenase and D-dimer levels may be useful as predictors of mirror syndrome.Impact statementWhat is already known on this subject? As mirror syndrome is uncommon and under-diagnosed, its exact incidence is not yet clear, and most publications are case reports or reviews of case reports.What the results of this study add? The incidence of mirror syndrome among all deliveries was 0.0162%, while that among patients with foetal hydrops was 23.2%. Pregnant women who develop mirror syndrome may show severe complications of pregnancy. Attention should be paid to the further progress of the condition. Placental thickness, placental weight and amniotic fluid index were significantly different between those with mirror syndrome and those without. In the mirror syndrome group, the uric acid, lactate dehydrogenase, creatinine and D-dimer levels were significantly higher (p < .05), whereas haemoglobin level, haematocrit value, platelet count and serum albumin level were significantly lower (p < .05).What the implications are of these findings for clinical practice and/or further research? Mirror syndrome is not rare among patients with foetal hydrops. Elevated uric acid, lactate dehydrogenase and D-dimer levels may be useful as predictors of mirror syndrome.


Asunto(s)
Edema/patología , Hidropesía Fetal/patología , Complicaciones del Embarazo/patología , Adulto , Edema/sangre , Edema/complicaciones , Femenino , Humanos , Placenta/patología , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/etiología , Estudios Retrospectivos , Síndrome
4.
J Ethnopharmacol ; 270: 113743, 2021 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-33359187

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Cannabis sativa L. is an aromatic annual herb belonging to the family Cannabaceae and it is widely distributed worldwide. Cultivation, selling, and consumption of cannabis and cannabis related products, regardless of its use, was prohibited in Lebanon until April 22, 2020. Nevertheless, cannabis oil has been traditionally used unlawfully for many years in Lebanon to treat diseases such as arthritis, diabetes, cancer and few neurological disorders. AIM OF THE STUDY: The present study aims to evaluate the phytochemical and anti-inflammatory properties of a cannabis oil preparation that is analogous to the illegally used cannabis oil in Lebanon. MATERIALS AND METHODS: Dried Cannabis flowers were extracted with ethanol without any purification procedures to simulate the extracts sold by underground dealers in Lebanon. GC/MS was performed to identify chemical components of the cannabis oil extract (COE). In vivo anti-inflammatory effect of COE was evaluated by using carageenan- and formalin-induced paw edema rat models. TNF-α production were determined by using LPS-activated rat monocytes. Anti-inflammatory markers were quantified using Western blot. RESULTS: Chemical analysis of COE revealed that cannabidiol (CBD; 59.1%) and tetrahydrocannabinol (THC; 20.2%) were found to be the most abundant cannabinoids.Various monoterpenes (α-Pinene, Camphene, ß-Myrecene and D-Limonene) and sesquiterpenes (ß-Caryophyllene, α-Bergamotene, α-Humelene, Humulene epoxide II, and Caryophyllene oxide) were identified in the extract. Results showed that COE markedly suppressed the release of TNF-α in LPS-stimulated rat monocytes. Western blot analysis revealed that COE significantly inhibited LPS-induced COX-2 and i-NOS protein expressions and blocked the phosphorylation of MAPKs, specifically that of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 MAPK. COE displayed a significant inhibition of paw edema in both rat models. Histopathological examination revealed that COE reduced inflammation and edema in chronic paw edema model. CONCLUSION: The current findings demonstrate that COE possesses remarkable in vivo and in vitro anti-inflammatory activities which support the traditional use of the Lebanese cannabis oil extract in the treatment of various inflammatory diseases including arthritis.


Asunto(s)
Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Cannabis/química , Edema/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios/química , Carragenina/toxicidad , Modelos Animales de Enfermedad , Edema/sangre , Edema/inducido químicamente , Edema/patología , Flores/química , Formaldehído/toxicidad , Inflamación/sangre , Inflamación/inducido químicamente , Inflamación/patología , Líbano , Lipopolisacáridos/toxicidad , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Fitoquímicos/química , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Extractos Vegetales/química , Cultivo Primario de Células , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo
5.
Artículo en Inglés | MEDLINE | ID: mdl-33010450

RESUMEN

Toll-like receptors (TLR) are crucial for recognizing bacterial, viral or fungal pathogens and to orchestrate the appropriate immune response. The widely expressed TLR2 and TLR4 differentially recognize various pathogens to initiate partly overlapping immune cascades. To better understand the physiological consequences of both immune responses, we performed comparative lipidomic analyses of local paw inflammation in mice induced by the TLR2 and TLR4 agonists, zymosan and lipopolysaccharide (LPS), respectively, which are commonly used in models for inflammation and inflammatory pain. Doses for both agonists were chosen to cause mechanical hypersensitivity with identical strength and duration. Lipidomic analysis showed 5 h after LPS or zymosan injection in both models an increase of ether-phosphatidylcholines (PC O) and their corresponding lyso species with additional lipids being increased only in response to LPS. However, zymosan induced stronger immune cell recruitment and edema formation as compared to LPS. Importantly, only in LPS-induced inflammation the lipid profile in the contralateral paw was altered. Fittingly, the plasma level of various cytokines and chemokines, including IL-1ß and IL-6, were significantly increased only in LPS-treated mice. Accordingly LPS induced distinct changes in the lipid profiles of ipsilateral and contralateral paws. Here, oxydized fatty acids, phosphatidylcholines and phosphatidylethanolamines were uniquely upregulated on the contralateral side. Thus, both models cause increased levels of PC O and lyso-PC O lipids at the site of inflammation pointing at a common role in inflammation. Also, LPS initiates systemic changes, which can be detected by changes in the lipid profiles.


Asunto(s)
Reacción de Fase Aguda/sangre , Edema/sangre , Lipopolisacáridos/administración & dosificación , Fosfatidilcolinas/sangre , Fosfatidiletanolaminas/sangre , Zimosan/administración & dosificación , Reacción de Fase Aguda/inducido químicamente , Reacción de Fase Aguda/genética , Reacción de Fase Aguda/patología , Animales , Edema/inducido químicamente , Edema/genética , Edema/patología , Ácidos Grasos/sangre , Ácidos Grasos/clasificación , Regulación de la Expresión Génica , Miembro Posterior/irrigación sanguínea , Miembro Posterior/efectos de los fármacos , Miembro Posterior/metabolismo , Interleucina-1beta/sangre , Interleucina-1beta/genética , Interleucina-6/sangre , Interleucina-6/genética , Lipidómica/métodos , Ratones , Ratones Endogámicos C57BL , Fosfatidilcolinas/clasificación , Fosfatidiletanolaminas/clasificación , Transducción de Señal , Receptor Toll-Like 2/sangre , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/sangre , Receptor Toll-Like 4/genética
6.
BMJ Case Rep ; 13(12)2020 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-33370989

RESUMEN

A 64-year-old man had a several year history of B prolymphocytic leukaemia (PLL) which behaved indolently and had not required any treatment. Five years after diagnosis, he developed hypoalbuminaemia associated with severe lower-limb oedema, consistent with systemic capillary leak syndrome (SCLS). He recovered spontaneously but went on to have three further increasingly severe and protracted episodes over the subsequent 18 months. There was no identifiable precipitating factor for these episodes, but his peripheral lymphocyte count continued to increase slowly. The start of treatment for his PLL with chemoimmunotherapy was followed by a rapid resolution of residual oedema and normalisation of serum albumin. He has had no further attacks of SCLS in the 14 months since he started therapy for PLL. SCLS is a rare consequence of haematological malignancy which may show an excellent response to treatment of the haematological disease.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Síndrome de Fuga Capilar/etiología , Edema/etiología , Hipoalbuminemia/etiología , Leucemia Prolinfocítica Tipo Células B/complicaciones , Síndrome de Fuga Capilar/sangre , Síndrome de Fuga Capilar/diagnóstico , Síndrome de Fuga Capilar/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Edema/sangre , Edema/diagnóstico , Edema/tratamiento farmacológico , Humanos , Hipoalbuminemia/sangre , Hipoalbuminemia/diagnóstico , Leucemia Prolinfocítica Tipo Células B/sangre , Leucemia Prolinfocítica Tipo Células B/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Rituximab/uso terapéutico , Albúmina Sérica Humana/análisis , Resultado del Tratamiento , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico
7.
Daru ; 28(1): 263-269, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32291620

RESUMEN

BACKGROUND: Some physicians co-administer albumin with loop diuretics to overcome diuretic resistance in critically ill hypoalbuminemia patients, though previous studies have reported conflicting results on this matter. OBJECTIVE: The effects of adding albumin to furosemide to enhance its efficacy in critically ill hypoalbuminemia patients are evaluated. METHODS: This was a non-blinded randomized trial. 49 adult critically ill patients with hypoalbuminemia and generalized edema who received randomly furosemide and furosemide/albumin complex were enrolled. The patients' urine was collected at intervals of 2, 4, 6 and 8 h after initiation of the furosemide treatment, and the urine output and urinary excretion of furosemide and sodium were measured. The urinary excretion of furosemide was considered an indicator of drug efficacy. RESULTS: The amount of sodium and furosemide excreted in urine showed no significant differences between the two groups; however, the mean of the urinary excretion of furosemide in the first 2 h after drug infusion was significantly higher (p = 0.03) in the furosemide/albumin group. No significant correlation between APACHE II scores and serum albumin levels and the urinary excretion of furosemide was seen. CONCLUSION: The results indicated that there is not statistically significant differences between groups with furosemide alone and combined with albumin in urinary furosemide excretion. It seems that adding albumin for furosemide pharmacotherapy regime is not recommended as an intervention to increase furosemide efficacy in critically ill hypoalbuminemia patients. TRIAL REGISTRATION: IRCT with the registration number IRCT201412132582N12 in 23 February 2015; https://en.irct.ir/trial/2356 Graphical abstract.


Asunto(s)
Diuréticos/administración & dosificación , Edema/tratamiento farmacológico , Furosemida/administración & dosificación , Hipoalbuminemia/tratamiento farmacológico , Albúmina Sérica/administración & dosificación , Anciano , Anciano de 80 o más Años , Enfermedad Crítica , Diuréticos/farmacocinética , Edema/sangre , Edema/orina , Femenino , Furosemida/farmacocinética , Humanos , Hipoalbuminemia/sangre , Hipoalbuminemia/orina , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Albúmina Sérica/análisis , Albúmina Sérica/farmacocinética , Resultado del Tratamiento
8.
BMC Pulm Med ; 20(1): 106, 2020 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-32334550

RESUMEN

BACKGROUND: Mechanical ventilation (MV), compared to spontaneous breathing (SB), has been found to increase abdominal edema and inflammation in experimental sepsis. Our hypothesis was that in primary acute respiratory distress syndrome (ARDS) MV would enhance inflammation and edema in the abdomen. METHODS: Thirteen piglets were randomized into two groups (SB and MV) after the induction of ARDS by lung lavage and 1 h of injurious ventilation. 1. SB: continuous positive airway pressure 15 cmH2O, fraction of inspired oxygen (FIO2) 0.5 and respiratory rate (RR) maintained at about 40 cycles min- 1 by titrating remifentanil infusion. 2. MV: volume control, tidal volume 6 ml kg- 1, positive end-expiratory pressure 15 cmH2O, RR 40 cycles min- 1, FIO2 0.5. MAIN OUTCOMES: abdominal edema, assessed by tissues histopathology and wet-dry weight; abdominal inflammation, assessed by cytokine concentration in tissues, blood and ascites, and tissue histopathology. RESULTS: The groups did not show significant differences in hemodynamic or respiratory parameters. Moreover, edema and inflammation in the abdominal organs were similar. However, blood IL6 increased in the MV group in all vascular beds (p < 0.001). In addition, TNFα ratio in blood increased through the lungs in MV group (+ 26% ± 3) but decreased in the SB group (- 17% ± 3). CONCLUSIONS: There were no differences between the MV and SB group for abdominal edema or inflammation. However, the systemic increase in IL6 and the TNFα increase through the lungs suggest that MV, in this model, was harmful to the lungs.


Asunto(s)
Edema/patología , Inflamación/patología , Respiración Artificial/efectos adversos , Síndrome de Dificultad Respiratoria/patología , Síndrome de Dificultad Respiratoria/terapia , Abdomen/patología , Animales , Ascitis/sangre , Ascitis/patología , Presión de las Vías Aéreas Positiva Contínua , Modelos Animales de Enfermedad , Edema/sangre , Inflamación/sangre , Interleucina-6/sangre , Masculino , Distribución Aleatoria , Respiración , Porcinos , Factor de Necrosis Tumoral alfa/sangre
9.
Arch Cardiovasc Dis ; 113(5): 332-340, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32151555

RESUMEN

BACKGROUND: Chronic peripheral oedema is frequent in old patients, and very often results from multiple causes. AIM: To investigate whether determination of B-type natriuretic peptide plasma concentration helps with the diagnosis of chronic peripheral oedema aetiologies. METHODS: This was a cross-sectional observational study conducted in geriatric hospital wards (intermediate and long-term care) on consecutive in-hospital patients aged>75 years with chronic peripheral oedema and no dyspnoea. From medical history, physical examination, routine biological tests and chest radiography, two investigators determined the aetiologies of oedema, with special attention paid to recognizing chronic heart failure. This reference diagnosis was compared with the clinical diagnosis mentioned in the medical chart. Brain natriuretic peptide plasma concentrations were measured soon after the investigators' visit. RESULTS: Among the 141 patients (113 women and 28 men) aged 86±6 years, a single aetiology was identified in 53 (38%), and multiple aetiologies in 84 (60%). The main aetiologies were venous insufficiency (69%), chronic heart failure (43%), hypoproteinaemia (38%) and drug-induced oedema (26%). Chronic heart failure was frequently misdiagnosed by attending clinicians (missed in 18 cases and wrongly diagnosed in 14 cases). Brain natriuretic peptide concentration was significantly higher in patients with chronic heart failure than in those without: median (interquartile range) 490 (324-954) versus 137 (79-203) pg/mL, respectively (P<0.0001). The receiver operating characteristic curve showed that a concentration of 274pg/mL was appropriate for diagnosing chronic heart failure, with a specificity of 0.89 and a sensitivity of 0.82. Brain natriuretic peptide concentrations above this cut-off were significantly and independently associated with the diagnosis of chronic heart failure. CONCLUSIONS: Chronic heart failure is frequently misdiagnosed in old patients with chronic peripheral oedema, and B-type natriuretic peptide plasma concentration helped to improve the diagnosis of this condition and identify chronic heart failure.


Asunto(s)
Edema/diagnóstico , Insuficiencia Cardíaca/diagnóstico , Péptido Natriurético Encefálico/sangre , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedad Crónica , Estudios Transversales , Edema/sangre , Edema/etiología , Edema/terapia , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Factores de Riesgo
11.
Sci Rep ; 9(1): 18328, 2019 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-31797976

RESUMEN

Morbidity in patients with single-ventricle Fontan circulation is common and includes arrhythmias, edema, and pulmonary arteriovenous malformations (PAVM) among others. We sought to identify biomarkers that may predict such complications. Twenty-five patients with Fontan physiology and 12 control patients with atrial septal defects (ASD) that underwent cardiac catheterization were included. Plasma was collected from the hepatic vein and superior vena cava and underwent protein profiling for a panel of 20 analytes involved in angiogenesis and endothelial dysfunction. Ten (40%) of Fontan patients had evidence of PAVM, eighteen (72%) had a history of arrhythmia, and five (20%) were actively in arrhythmia or had a recent arrhythmia. Angiopoietin-2 (Ang-2) was higher in Fontan patients (8,875.4 ± 3,336.9 pg/mL) versus the ASD group (1,663.6 ± 587.3 pg/mL, p < 0.0001). Ang-2 was higher in Fontan patients with active or recent arrhythmia (11,396.0 ± 3,457.7 vs 8,118.2 ± 2,795.1 pg/mL, p < 0.05). A threshold of 8,500 pg/mL gives Ang-2 a negative predictive value of 100% and positive predictive value of 42% in diagnosing recent arrhythmia. Ang-2 is elevated among adults with Fontan physiology. Ang-2 level is associated with active or recent arrhythmia, but was not found to be associated with PAVM.


Asunto(s)
Angiopoyetina 2/sangre , Arritmias Cardíacas/sangre , Proteínas Sanguíneas/genética , Edema/sangre , Procedimiento de Fontan , Adulto , Angiopoyetina 2/genética , Arritmias Cardíacas/patología , Fístula Arteriovenosa/sangre , Malformaciones Arteriovenosas/sangre , Malformaciones Arteriovenosas/fisiopatología , Biomarcadores/sangre , Cateterismo Cardíaco , Edema/patología , Células Endoteliales/metabolismo , Células Endoteliales/patología , Femenino , Defectos del Tabique Interatrial/sangre , Defectos del Tabique Interatrial/patología , Humanos , Masculino , Neovascularización Fisiológica , Arteria Pulmonar/anomalías , Venas Pulmonares/anomalías
13.
Biomed Pharmacother ; 118: 109347, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31545273

RESUMEN

λ-Carrageenan (Carr), a seaweed polysaccharide, is used as a proinflammatory agent in research. Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid, exerts immunomodulatory, antioxidant, anti-inflammatory, antitumor, anti-malarial and anti-HIV effects. The aim of this study was to investigate whether BA exerts anti-inflammatory effect against Carr-induced paw edema in mice, and how BA could mediate the expression of inflammation-associated MAPK-COX-2-PGE2 signal pathway. BA pretreatment significantly reduced the inflammatory response to Carr-induced paw edema, especially at 4 h after injection. BA reduced the serum levels of pro-inflammatory cytokines, such as IL-1α, IL-1ß, IL-5, IL-6, GM-CSF, KC, MCP-1 and PGE2 in Carr-treated mice, and increased those of anti-inflammatory cytokines, such as IL-12. It also increased SOD, CAT and GSH-Px activities, and GSH content, and reduced MDA content in the liver of Carr-treated mice. Besides, BA reduced neutrophil infiltration in the basal and subcutaneous layers of the paw of Carr-treated mice, decreased the expression of COX-2 protein, and reduced the phosphorylation of JNK, p38 and ERK1/2. These results indicated that the protective effect of BA on Carr-induced paw edema might be due to its alleviation of inflammatory response and inhibition of oxidative stress, possibly by inhibiting MAPK-COX-2-PGE2 signaling pathway activation.


Asunto(s)
Antiinflamatorios/uso terapéutico , Edema/tratamiento farmacológico , Extremidades/patología , Triterpenos/uso terapéutico , Animales , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Carragenina , Ciclooxigenasa 2/metabolismo , Citocinas/sangre , Dinoprostona/sangre , Edema/sangre , Edema/inducido químicamente , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Triterpenos Pentacíclicos , Fosforilación/efectos de los fármacos , Triterpenos/farmacología , Ácido Betulínico
14.
Int J Mol Sci ; 20(16)2019 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-31404946

RESUMEN

Heart failure (HF) patients frequently have elevated plasma renin activity. We examined the significance of elevated plasma renin activity in a translationally-relevant model of dilated cardiomyopathy (DCM), which replicates the progressive stages (A-D) of human HF. Female mice with DCM and elevated plasma renin activity concentrations were treated with a direct renin inhibitor (aliskiren) in a randomized, blinded fashion beginning at Stage B HF. By comparison to controls, aliskiren treatment normalized pathologically elevated plasma renin activity (p < 0.001) and neprilysin levels (p < 0.001), but did not significantly alter pathological changes in plasma aldosterone, angiotensin II, atrial natriuretic peptide, or corin levels. Aliskiren improved cardiac systolic function (ejection fraction, p < 0.05; cardiac output, p < 0.01) and significantly reduced the longitudinal development of edema (extracellular water, p < 0.0001), retarding the transition from Stage B to Stage C HF. The normalization of elevated plasma renin activity reduced the loss of body fat and lean mass (cachexia/sarcopenia), p < 0.001) and prolonged survival (p < 0.05). In summary, the normalization of plasma renin activity retards the progression of experimental HF by improving cardiac systolic function, reducing the development of systemic edema, cachexia/sarcopenia, and mortality. These data suggest that targeting pathologically elevated plasma renin activity may be beneficial in appropriately selected HF patients.


Asunto(s)
Amidas/uso terapéutico , Cardiomiopatía Dilatada/tratamiento farmacológico , Fumaratos/uso terapéutico , Renina/antagonistas & inhibidores , Renina/sangre , Animales , Caquexia/sangre , Caquexia/complicaciones , Caquexia/tratamiento farmacológico , Cardiomiopatía Dilatada/sangre , Cardiomiopatía Dilatada/complicaciones , Modelos Animales de Enfermedad , Edema/sangre , Edema/complicaciones , Edema/tratamiento farmacológico , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Ratones , Ratones Endogámicos C57BL
15.
Biol Pharm Bull ; 42(8): 1419-1422, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31366877

RESUMEN

The pathogenic relationship of ulcerative colitis and rheumatoid arthritis is not known. Therefore, we examined dextran sodium sulfate (DSS)-induced colitis separately and in combination with a mouse arthritis model that mimics rheumatoid arthritis and evaluated the deterioration-related factors of each condition. Arthritis was induced in a collagen-induced arthritis mouse model using DBA/1JJmsSlc mice and ulcerative colitis was induced by the administration of drinking water containing 3.0% (w/v) DSS. The arthritis/DSS-treated mice developed worse colitis scores compared to that of the other groups of mice. The arthritis/DSS-treated mice did not demonstrate changes in hind foot volumes or in the concentration of matrix metalloproteinase-3 (MMP-3) in the plasma; however, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α were increased. Our results showed that IL-6 and TNF-α may influence the deterioration effect of colitis in arthritic mice.


Asunto(s)
Artritis Experimental/inmunología , Colitis Ulcerosa/inmunología , Interleucina-6/sangre , Factor de Necrosis Tumoral alfa/sangre , Animales , Artritis Experimental/sangre , Artritis Experimental/patología , Colitis Ulcerosa/sangre , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/patología , Colon/patología , Sulfato de Dextran , Edema/sangre , Edema/inmunología , Edema/patología , Pie/patología , Metaloproteinasa 3 de la Matriz/sangre , Ratones Endogámicos DBA
16.
Mediators Inflamm ; 2019: 3041438, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31263381

RESUMEN

Despite the usefulness of glucocorticoids, they may cause hazardous side effects that limit their use. Searching for compounds that are as equally efficient as glucocorticoids, but with less side effects, the current study compared plant steroids, namely, glycyrrhetinic acid, guggulsterone, boswellic acid, withaferin A, and diosgenin with the classical glucocorticoid, fluticasone. This was approached both in silico using molecular docking against glucocorticoid receptor (GR) and in vivo in two different animal models. All tested compounds interacted with GR, but only boswellic acid and withaferin A showed docking results comparable to fluticasone, as well as similar in vivo anti-inflammatory effects, by significantly decreasing serum levels of interleukin-6 and tumor necrosis factor-α in cotton pellet-induced granuloma in rats. In addition, both compounds significantly decreased the percent of change in ear weight in croton oil-induced ear edema in mice and the granuloma weight in cotton pellet-induced granuloma in rats, to levels comparable to that of fluticasone. Both boswellic acid and withaferin A had no effect on adrenal index, but only withaferin A significantly increased the thymus index. In conclusion, boswellic acid may have comparable anti-inflammatory effects to fluticasone with fewer side effects.


Asunto(s)
Enfermedades del Oído/tratamiento farmacológico , Enfermedades del Oído/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Fitosteroles/uso terapéutico , Receptores de Glucocorticoides/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Aceite de Crotón/toxicidad , Diosgenina/uso terapéutico , Enfermedades del Oído/sangre , Enfermedades del Oído/inducido químicamente , Edema/sangre , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/metabolismo , Ensayo de Inmunoadsorción Enzimática , Ácido Glicirretínico/uso terapéutico , Inflamación/inducido químicamente , Inflamación/inmunología , Interleucina-6/sangre , Ratones , Simulación del Acoplamiento Molecular , Pregnenodionas/uso terapéutico , Ratas , Programas Informáticos , Timo/efectos de los fármacos , Timo/metabolismo , Triterpenos/uso terapéutico , Factor de Necrosis Tumoral alfa/sangre , Witanólidos/uso terapéutico
17.
J Med Invest ; 66(1.2): 112-118, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31064921

RESUMEN

Polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome are common inflammatory rheumatic diseases in the elderly. In this study, we investigate predictive factors which correspond to subsequent disease control of PMR and RS3PE syndrome. Twenty four patients, which contained 18 PMR and 6 RS3PE syndrome, were treated with initial dosages of 10-20 mg per day oral prednisolone, and the dosage of prednisolone was then tapered. Significantly higher initial CRP was observed in patients with poor disease control than in those with good disease control afterwards. The number of patients with negative CRP after 4 weeks was significantly more in patients with good disease control after 1 year than in those with poor disease control. Patients were shown to be in good disease control status after 1 year when CRP after 4 weeks became negative even if they had initial high CRP. Our study clarify that to make CRP negative after 4 weeks is associated with subsequent suppression of the disease activity and with decreased dosages of corticosteroids. J. Med. Invest. 66 : 112-118, February, 2019.


Asunto(s)
Edema/tratamiento farmacológico , Polimialgia Reumática/tratamiento farmacológico , Prednisolona/uso terapéutico , Sinovitis/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Edema/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimialgia Reumática/sangre , Estudios Retrospectivos , Síndrome , Sinovitis/sangre
18.
Indian Heart J ; 71(1): 32-38, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31000180

RESUMEN

BACKGROUND: Despite several decades of use of calcium channel blockers, the side effect of edema persists as a class effect, and its mechanism is unresolved. Amlodipine has effects on hemorheology (HR), and its hemodilutory property may partly contribute to its antihypertensive action. This aspect is not well studied, and the literature is sparse in this regard. OBJECTIVE: This experiment was planned to determine effect of a single-dose administration of amlodipine on HR parameters in normal human volunteers. METHODS AND RESULTS: Amlodipine (5 mg) or S (-) amlodipine (2.5 mg) was administered to 27 normal human volunteers. Whole-blood viscosity (WBV) at different shear rates, plasma viscosity (PV), red cell rigidity (RCR), red cell aggregation (RCA), hematocrit (Hct), plasma hemoglobin, along with plasma drug concentration were determined at time intervals, t = 0, 4, 8, 12, and 24 h. Statistically significant reductions were observed at tmax = 4 h in WBV at shear rates of 0.512 s-1 (p < 0.005), WBV at shear rates of 5.26 s-1 (p < 0.01), PV (p < 0.05), and Hct (p < 0.01). At t = 8 h, as drug concentration reduced, some of the changes persisted and later slowly decreased with the decreasing drug concentration till t = 24 h. Red blood cell-related parameters such as RCA and RCR remained unaltered. WBV values at all shear rates, when corrected for Hct = 0.45, did not show deviation from their original values at any time. CONCLUSIONS: Amlodipine causes a reduction in Hct and blood viscosity, along with hemodilution. These effects persist as long as the drug remains in plasma. Edema resulting from chronic dosing may be explained by the aforementioned effects. It is possible that antihypertensive action of the drug may be due to a combination of vasodilatation and an improvement in the HR properties.


Asunto(s)
Amlodipino/administración & dosificación , Viscosidad Sanguínea/efectos de los fármacos , Edema/sangre , Agregación Eritrocitaria/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/administración & dosificación , Relación Dosis-Respuesta a Droga , Edema/tratamiento farmacológico , Edema/etiología , Voluntarios Sanos , Hematócrito , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Masculino , Método Simple Ciego , Resultado del Tratamiento , Adulto Joven
19.
Indian J Pharmacol ; 51(1): 25-30, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31031464

RESUMEN

OBJECTIVE: Bauhinia purpurea (BP) Linn. (Caesalpiniaceae) is a plant of great medicinal importance and has been used since ancient times for treating many inflammatory conditions including arthritis. This study investigates the anti-arthritic potential of the hydroalcoholic extract from the stem bark of BP. MATERIALS AND METHODS: The anti-inflammatory and anti-arthritic activity of BP at various doses was used to evaluate its anti-inflammatory activity and anti-arthritic activity. Serum of arthritic rats was collected at day 21 for detecting serum cytokines level and to evaluate the effect of BP on its serum level. Furthermore, the safety of BP was evaluated in acute (5 days) and subacute (28 days) toxicity study in rats. RESULTS: There was a significant inhibition (P < 0.01) in paw edema at a different time scale with different doses of BP (50, 100, and 200 mg/kg). BP also demonstrated dose-dependent anti-arthritic activity on all observation days (3, 7, 14, and 21). In addition, there was also a significant decrease (P < 0.01) in oxidative stress markers, circulating pro-inflammatory cytokine (tumor necrosis factor alpha from 45.91 to 37.44, interleukin-1 (IL-1) ß from 18.24 to 16.06, and IL-6 from 69.77 to 58.44) and an increase in anti-inflammatory cytokine (IL-10 from 8.07 to 12.07) levels. BP was found to be safe with an oral LD50 value of >2 g/kg in acute toxicity study and also no toxicological effect was observed in the oral subacute toxicity study. CONCLUSION: This study demonstrates that BP bark possesses anti-arthritic activity potential and confirm its folklore use in the treatment of inflammatory conditions.


Asunto(s)
Antiinflamatorios/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Bauhinia , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios/farmacología , Artritis Experimental/sangre , Citocinas/sangre , Edema/sangre , Edema/tratamiento farmacológico , Masculino , Extractos Vegetales/farmacología , Ratas Wistar , Pruebas de Toxicidad Subaguda
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