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BACKGROUND: Obesity is a crucial factor that increases the risk of initiating and advancing knee osteoarthritis. However, it remains unclear how obesity directly impacts the biomechanical experience of the lower limb joints, potentially triggering or exacerbating joint degeneration. This study investigated the interactive effects of BMI augmentation on lower limb kinematics, kinetics, and muscle activations during walking. METHODOLOGY: A group of 60 participants underwent a three-dimensional gait analysis. These individuals were categorized into three groups based on their body mass index (BMI): those with a BMI below 25 were classified as having a healthy weight, those with a BMI between 25 and 30 were categorized as overweight, and those with a BMI exceeding 30 were considered obese. This study analyzed the gait of 60 participants categorized by BMI. During walking trials, they recorded ground reaction forces electromyography of leg muscles like the gastrocnemii, hamstrings, and quadriceps. Lower limb joint angles and net moments were also calculated. Statistical mapping identified variations in kinematic, kinetic, and muscle activation patterns across the stance phase between BMI groups. RESULTS: The results displayed distinct biomechanical patterns in obese individuals. Notably, there was a significant increase in flexion observed in the hip and knee joints (P < 0.001) during the initial stance phase and an increase in hip and knee adduction angles and moments throughout the entire stance phase (P < 0.001). Additionally, muscle activations underwent significant changes (P < 0.01), with a positive correlation noted with the BMI factor. This correlation was most pronounced during the early stance phase for the quadriceps and hamstring muscles and the late stance phase for the gastrocnemius. CONCLUSION: These findings represent a comprehensive picture that contributes to understanding how excess weight and obesity influence joint biomechanics, highlighting the associated risk of joint osteoarthritis.
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Knee osteoarthritis (OA) and obesity are major public health concerns that are closely intertwined. This intimate relationship was documented by considering obesity as the most significant preventable risk factor associated with knee OA. To date, however, the effects of obesity on the knee joint's passive-active structure and cartilage loading have been inconclusive. Hence, this study investigates the intricate relationship between obesity and knee OA, centering on the biomechanical changes in knee joint active and passive reactions during the stance phase of gait. Using a subject-specific musculoskeletal and finite element approach, muscle forces, ligament stresses, and articular cartilage contact stresses were analyzed among 60 individuals with different body mass indices (BMI) classified under healthy weight, overweight, and obese categories. Our predicted results showed that obesity significantly influenced knee joint mechanical reaction, increasing muscle activations, ligament loading, and articular cartilage contact stresses, particularly during key instances of the gait cycle-first and second peak loading instances. The study underscores the critical role of excessive body weight in exacerbating knee joint stress distribution and cartilage damage. Hence, the insights gained provide a valuable biomechanical perspective on the interaction between body weight and knee joint health, offering a clinical utility in assessing the risks associated with obesity and knee OA.
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Peso Corporal , Análisis de Elementos Finitos , Marcha , Articulación de la Rodilla , Obesidad , Osteoartritis de la Rodilla , Humanos , Articulación de la Rodilla/fisiología , Fenómenos Biomecánicos , Obesidad/fisiopatología , Osteoartritis de la Rodilla/fisiopatología , Masculino , Marcha/fisiología , Femenino , Cartílago Articular/fisiología , Adulto , Índice de Masa Corporal , Persona de Mediana EdadRESUMEN
Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.
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Síndrome de Sjögren , Humanos , Resultado del Tratamiento , Síndrome de Sjögren/terapia , Dolor , FatigaRESUMEN
Coumarins and their derivatives are becoming a potential source for new drug discovery due to their vast array of biological activities. The present study was designed to investigate the cardioprotective effects of a newly synthesised coumarin, symbolised as 5,6-PhSHC, against cardiac remodelling process in isoproterenol (ISO) induced myocardial infarction (MI) in male Wistar rats by evaluating haematological, biochemical and cardiac biomarkers. Rats were pre/co-treated with 5,6-PhSHC or clopidogrel (150 µg/kg body weight) daily for a period of 7 days and then MI was induced by injecting ISO (85 mg/kg body weight), at an interval of 24 hours for 2 consecutive days, on the sixth and seventh days. The in vivo exploration indicated that the injection of 5,6-PhSHC improved the electrocardiographic (ECG) pattern and prevented severe heart damage by reducing leakage of the cardiac injury markers, such as troponin-T (cTn-T), lactate dehydrogenase (LDH), and creatine kinase-MB. The cellular architecture of cardiac sections, altered in the myocardium of infracted rats, was reversed by 5,6-PhSHC treatment. Results showed that injection of 5,6-PhSHC elicited significant cardioprotective effects by prevention of myocardium cell necrosis and inflammatory cells infiltration, along with marked decrease in plasma levels of fibrinogen. In addition, the total cholesterol, triglyceride, LDL-c, and HDL profiles underwent remarkable beneficial changes. It was also interesting to note that 5,6-PhSHC enhanced the antioxidative defence mechanisms by increasing myocardial glutathione (GSH) level, superoxide dismutase (SOD), and catalase (CAT) activities, together with reducing the levels of thiobarbituric-acid-reactive substances (TBARS), when compared with ISO-induced rats. Taken together, these findings suggested a beneficial role for 5,6-PhSHC against ISO-induced MI in rats. Furthermore, in silico analysis showed that 5,6-PhSHC possess high computational affinities (E-value >-9.0 kcal/mol) against cyclooxygenase-2 (PDB-ID: 1CX2), vitamin K epoxide reductase (PDB-ID: 3KP9), glycoprotein-IIb/IIIa (PDB-ID: 2VDM) and catalase (PDB-ID: 1DGF). Therefore, the present study provided promising data that the newly synthesised coumarin can be useful in the design and synthesis of novel drug against myocardial infarction.
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Infarto del Miocardio , Animales , Antioxidantes/metabolismo , Peso Corporal , Cardiotónicos/efectos adversos , Catalasa/metabolismo , Cumarinas/farmacología , Cumarinas/uso terapéutico , Electrocardiografía , Glutatión/metabolismo , Isoproterenol/efectos adversos , Masculino , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/prevención & control , Miocardio/metabolismo , Estrés Oxidativo , Ratas , Ratas WistarRESUMEN
This study was designed to evaluate the underlying protective mechanisms of oleuropein involved in alleviating brain damage in a rat model of ischemic stroke. Male Wistar rats were divided into four groups; Control, stroke (MCAO), MCAO + clopidogrel (Clop) and MCAO + oleuropein (Ole). Results showed that the MCAO group evidenced significant brain edema (+ 9%) as well as increases of plasma cardiac markers such as lactate deshydrogenase (LDH), creatine kinase (CK-MB), fibrinogen and Trop-T by 11 %, 43%, 168 and 590%, respectively, as compared to the control group. Moreover, infarcted rats exhibited remarkable elevated levels of angiotensin converting enzyme (ACE), both in plasma and brain tissue, with astrocyte swelling and necrotic neurons in the infarct zone, hyponatremia, and increased rate of thiobarbituric acid-reactive substances (TBARS) by 89% associated with decreases in the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (Cat) by 51%, 44 and 42%, respectively, compared to normal control rats. However, MCAO rats treated with oleuropein underwent mitigation of cerebral edema, correction of hyponatremia, remarkable decrease of plasma fibrinogen and cardiac dysfunctional enzymes, inhibition of ACE activity and improvement of oxidative stress status in brain tissue. Furthermore, in silico analysis showed considerable inhibitions of ACE, protein disulfide isomerase (PDI) and TGF-ß1, an indicative of potent anti-embolic properties. Overall, oleuropein offers a neuroprotective effect against ischemic stroke through its antioxidative and antithrombotic activities.
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Depuradores de Radicales Libres/uso terapéutico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Glucósidos Iridoides/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Acetilcolinesterasa/metabolismo , Animales , Encéfalo/patología , Edema Encefálico/patología , Edema Encefálico/prevención & control , Clopidogrel/uso terapéutico , Depuradores de Radicales Libres/metabolismo , Humanos , Hiponatremia/prevención & control , Infarto de la Arteria Cerebral Media/patología , Glucósidos Iridoides/metabolismo , Masculino , Simulación del Acoplamiento Molecular , Fármacos Neuroprotectores/metabolismo , Estrés Oxidativo/efectos de los fármacos , Peptidil-Dipeptidasa A/metabolismo , Unión Proteica , Proteína Disulfuro Isomerasas/metabolismo , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
OBJECTIVE: Towards developing an instrument to measure knee and hip osteoarthritis (KHOA) flare, the Outcome Measures in Rheumatology (OMERACT) Flares in OA Working Group first sought to identify and define relevant domains of flare in KHOA. METHODS: Guided by OMERACT Filter 2.1, candidate domains were identified from data generated in interviews, in English or French, with persons with KHOA and health professionals (HPs) who treat OA. The first and second rounds of an online Delphi process with patients and HPs, including researchers, selected relevant domains. The third round provided agreement on the selected domains and their definitions. At the virtual OMERACT 2020 workshop, the proposed domains and their definitions were discussed in facilitated breakout groups with patients and HPs. Participants then voted, with consensus set at ≥70%. RESULTS: Qualitative interviews characterizing OA flare were completed with 29 persons with KHOA and 16 HPs. Content was analyzed and grouped into nine clusters. These candidate domains were included in two Delphi rounds, completed by 91 patients and 165 HPs then 50 patients and 116 HPs, per round, respectively. This resulted in selecting five relevant domains. A final Delphi round, completed by 38 patients and 89 HPs, provided agreement on these domains and their definitions. The OMERACT virtual vote included 27 patients and 106 HPs. The domains and their definitions were endorsed with ≥98% agreement. Domains include: Pain, Swelling, Stiffness, Psychological aspects, and Impact of symptoms, all defined "during flare". CONCLUSION: Using OMERACT methodology, we have developed five domains of KHOA flare that were highly endorsed by patients and HPs.
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Osteoartritis de la Cadera , Osteoartritis de la Rodilla , Reumatología , Consenso , Humanos , Articulación de la RodillaRESUMEN
This study is carried out to assess the cardiopreventive effect of (E)-N'-(1-(7-methoxy-2-oxo-2H-chromen-3-yl) ethylidene)-4-methylbenzenesulfonohydrazide or SHC, a novel synthesized coumarin, against myocardial infarction induced by isoproterenol (ISO). The SHC compound was identified and characterized by spectral methods (infrared, 1 H NMR [nuclear magnetic resonance], 13 C NMR, Nuclear Overhauser Effect Spectroscopy, and high-resolution mass spectroscopy). Male Wistar rats were divided into four groups: Control, ISO (rats were injected subcutaneously by 85 mg/kg body weight [BW] of isoproterenol at Days 6 and 7 of the experience), ISO + SHC (150 µg/kg BW, orally for 7 days) and ISO + acenocoumarol (150 µg/kg BW, orally for 7 days). Results showed that ISO induced a remarkable alteration of electrocardiogram (ECG) pattern and increases of plasma cardiac troponin T, creatine kinase-MB, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, lactate dehydrogenase, aspartate transaminase, and malondialdehyde. In addition, ISO reduced the high-density lipoprotein-cholesterol content and the activities of superoxide dismutase and glutathione peroxidase, with the induction of myocardial necrosis. However, SHC administration revealed a significant decrease in cardiac dysfunction markers, restored normal ECG pattern, as well as improving lipids parameters. Moreover, SHC treatment remarkably alleviated the cardiac oxidative stress and the myocardial remodeling process. Overall, the SHC offers good protection from acute myocardial infarction through the antioxidant capacity.
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Bencenosulfonatos/farmacología , Cardiotónicos/farmacología , Isoproterenol/efectos adversos , Infarto del Miocardio , Miocardio , Estrés Oxidativo/efectos de los fármacos , Animales , Bencenosulfonatos/química , Cardiotónicos/química , Isoproterenol/farmacología , Masculino , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/prevención & control , Miocardio/metabolismo , Miocardio/patología , Ratas , Ratas WistarRESUMEN
Fibroblast growth factor 23 (FGF23) gene is found to be responsible for autosomal dominant hypophosphatemic rickets, and is highly expressed in chronic kidney disease (CKD) and end-stage renal disease patients with iron deficiency anemia (IDA). We evaluated the efficacy of different iron treatments on FGF23 levels in dialysis-dependent and non-dialysis-dependent CKD patients with IDA. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing different types of iron treatment versus placebo in CKD patients up to May 2020. We investigated the efficacy of iron treatment on the levels of FGF23 and C-terminal FGF23 (cFGF23) in CKD patients. We estimated weighted mean differences (WMDs) and 95% confidence intervals (CIs) using the random-effects model. Nine studies with 11 arms were included in the meta-analysis. Overall, iron treatment showed a significant reduction in FGF23 levels compared to control group (WMD: - 60.56 pg/ml, 95% CI: - 92.17, - 28.95). Compared to placebo, subgroup analysis showed that oral iron therapy (WMD: - 6.98 pg/ml, 95% CI: - 10.66, - 3.31) was more effective than intravenous (IV) iron therapy (WMD: 4.90 pg/ml, 95% CI: - 12.03, 21.83) on FGF23 levels. There was no significant change in cFGF23 levels between iron treatment and control group (WMD: - 64.72 Ru/ml, 95% CI: - 147.69, 18.25). Subgroup analysis showed that oral iron therapy resulted in a significant reduction in cFGF23 levels compared to control group (WMD: - 150.48 RU/ml, 95% CI: - 151.31, - 149.65). In conclusion, iron treatment was associated with a significant decrease in FGF23 levels in CKD patients.
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Hierro , Insuficiencia Renal Crónica , Suplementos Dietéticos , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos , Humanos , Insuficiencia Renal Crónica/tratamiento farmacológicoRESUMEN
This study aimed to evaluate the cerebroprotective potential of a novel synthetic coumarin, (E)-4-amino-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl)ethylidene) benzohydrazide noted (HC) against a pharmaceutically induced ischemic stroke in experimental male Wistar rats. Animals were randomly allocated into four groups: control, Stroke, Stroke + Ace (acenocoumarol) and Stroke + HC-treated group for 7 days. Our results showed that stroke group evidenced atrial flutter, significant cardiac hypertrophy (+23%) and increase in plasma level of troponin-T, with disturbance in plasma ionic levels and rise in fibrinogen rate and oxidative damages in heart and brain. Moreover, the histological findings revealed myocardium necrosis, cardiac cavity thrombi and brain injury as compared to normal rats. However, HC-treatment significantly prevents the embolic process, improves cerebral damages and mitigates the oxidative stress markers in stroke rats. Overall, HC is endowed with a thrombolytic potential against MI and stroke in such severe conditions through an anti-vit K (AVK) mechanism.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Isoproterenol , Masculino , Miocardio/metabolismo , Estrés Oxidativo , Ratas , Ratas Wistar , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/metabolismo , Vitamina K/metabolismo , VitaminasRESUMEN
This study aimed to explore the cardioprotective effect of new synthesized coumarin (E)-4-hydroxy-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide denoted (Hyd.Cou) against myocardial infarction disorders. Male Wistar rats were divided into four groups; Control, isoproterenol (ISO), ISO + Acenocoumarol (Ac) and ISO + Hyd.Cou. Results showed that the ISO group exhibited serious alteration in EGC pattern, significant heart hypertrophy (+33%), haemodynamic disturbance and increase in plasma rate of CK-MB, LDH and troponin-T by 44, 53, and 170%, respectively, as compared to Control. Moreover, isoproterenol induced a rise in plasma angiotensin-converting enzyme activity (ACE) by 49%, dyslipidaemia, and increased thiobarbituric acid-reactive substances (TBARS) by 117% associated with decrease in the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) by 46% and 58%, respectively in myocardium. Interestingly, the molecular docking calculation demonstrated strong interactions of Hyd.Cou with the receptors of the protein disulphide isomerase (PDI) which could highlight the antithrombotic effect. Moreover, Hyd.Cou improved plasma cardiac dysfunction biomarkers, mitigated the ventricle remodelling process and alleviated heart oxidative stress damage. Overall, Hyd.Cou prevented the heart from the remodelling process through inhibition of ACE activity and oxidative stress improvement.
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The current study was aimed to assess the protective effect of a new molecule (E)-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide, denoted 1c, against cardiac remodeling process in isoproterenol (Isop) induced myocardial infarction (MI) in rats. Male Wistar rats were randomly divided into four groups, control, Isop (85 mg/kg body weight was injected subcutaneously into rats at an interval of 24 h for 2 days (6th and 7th day) to induce MI and pretreated animals with acenocoumarol (Ace) (150 µg/kg bw) and 1c (150 µg/kg bw) by oral administration during 7 days and injected with isoproterenol (Isop + Ace) and (Isop + 1c) groups. Results in vitro showed that 1c is endowed with potent inhibition of angiotensin-converting enzyme (ACE) with an IC50 39.12 µg/ml. The in vivo exploration evidenced alteration in the ECG pattern, notable cardiac hypertrophy and increase in plasma level of fibrinogen, troponin-T, CK-MB and LDH, AST and ALT by 171%, 300%, 50%, 64% and 75% respectively with histological myocardium necrosis and cells inflammatory infiltration. However, pre-treatment with 1c improved the ECG pattern reduced significantly the cardiac dysfunction markers and ameliorated the thrombolytic process by decreasing fibrinogen level as compared to untreated infracted rats. Overall, (E)-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide 1c could be used as anticoagulant agent to prevent thrombosis in acute myocardial infarction.
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Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Fibrinolíticos/farmacología , Hidrazonas/farmacología , Infarto del Miocardio/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Inhibidores de la Enzima Convertidora de Angiotensina/síntesis química , Animales , Antiinflamatorios/síntesis química , Antiinflamatorios/farmacología , Biomarcadores/sangre , Cardiotoxicidad , Modelos Animales de Enfermedad , Fibrinógeno/metabolismo , Fibrinolíticos/síntesis química , Frecuencia Cardíaca/efectos de los fármacos , Hidrazonas/síntesis química , Isoproterenol , Lípidos/sangre , Masculino , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/metabolismo , Infarto del Miocardio/fisiopatología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Necrosis , Ratas Wistar , Remodelación Ventricular/efectos de los fármacosRESUMEN
The present study was directed to investigate the effect of precotreatment with (E)-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide (7-hyd.HC), a novel potent synthesized coumarin, on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. The hydrazone compound was characterized by IR, 1D, and 2D NMR analyses. Experimental induction of MI in rats was established by ISO (85 mg/kg/day, s.c) for two consecutive days (6th and 7th days). 7-hyd.HC or sintrom was given for 7 days prior and simultaneous to ISO injection. 7-hyd.HC offered a cardiopreventive effect by preventing heart injury marker leakage (LDH, ALT, AST, CK-MB, and cTn-I) from cardiomyocytes and normalizing cardiac function and ECG pattern, as well as improving lipid profile (TC, TG, LDL-C, and HDL-C), which were altered by ISO administration. Moreover, 7-hyd.HC precotreatment significantly mitigated the oxidative stress biomarkers, as evidenced by the decrease of lipid peroxidation and the increased level of the myocardial GSH level together with the SOD, GSH-Px, and catalase activities. 7-hyd.HC inhibited the cardiac apoptosis by upregulating the expression of Bcl-2 and downregulating the expression of Bax and caspase-3 genes. In addition, 7-hyd.HC reduced the elevated fibrinogen rate and better prevented the myocardial necrosis and improved the interstitial edema and neutrophil infiltration than sintrom. Overall, 7-hyd.HC ameliorated the severity of ISO-induced myocardial infarction through improving the oxidative status, attenuating apoptosis, and reducing fibrinogen production. The 7-hyd.HC actions could be mediated by its antioxidant, antiapoptotic, and anti-inflammatory capacities.
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Antiinflamatorios/uso terapéutico , Benzopiranos/uso terapéutico , Cumarinas/uso terapéutico , Hidrazonas/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Animales , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Apoptosis/efectos de los fármacos , Benzopiranos/síntesis química , Benzopiranos/química , Biomarcadores/metabolismo , Cumarinas/síntesis química , Cumarinas/química , Hidrazonas/síntesis química , Hidrazonas/química , Inflamación/metabolismo , Isoproterenol/toxicidad , Masculino , Estructura Molecular , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocardio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
The current study was carried out to evaluate the effect of pretreatment and co-treatment with a newly synthesized coumarin hydrazone, (E)-4-hydroxy-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide (hereinafter EK6), against isoproterenol-induced myocardial infarction in rats. Changes in biochemistry, cardiac biomarkers, electrocardiography, and histopathology after treatment with EK6 or acenocoumarol (Sintrom) were studied. Animals were randomly divided into 4 groups: vehicle control (C), isoproterenol + Sintrom (ISO + Sin), isoproterenol + EK6 (ISO + EK6), and isoproterenol (ISO). Myocardial infarction was induced by subcutaneous ISO administration at a dose of 85 mg·kg-1·day-1 with a drug-free interval of 24 h on days 6 and 7. Treatment with ISO led to significant elevation (p < 0.05) in serum levels of cardiac injury biomarkers, namely cardiac troponin-T, lactate dehydrogenase, creatine kinase-MB, alanine aminotransferase, and aspartate aminotransferase compared with levels in the vehicle control. A change in the lipid profile was also observed as a significant increase in total cholesterol and triglycerides. Furthermore, ISO caused significant alterations in the electrocardiogram pattern, including significant ST-segment elevation, significant decreased R wave amplitude, and significant increase in heart rate (16%) as well as marked changes in the histopathology of the heart tissue. Pretreatment and co-treatment with newly synthesized coumarin hydrazone restored all ISO-induced biochemical, lipid, cardiac, and histopathological changes in rats with myocardial infarction.
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Benzopiranos/administración & dosificación , Cardiotónicos/administración & dosificación , Cumarinas/administración & dosificación , Hidrazonas/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Animales , Benzopiranos/síntesis química , Biomarcadores/análisis , Cardiotónicos/síntesis química , Cumarinas/síntesis química , Modelos Animales de Enfermedad , Electrocardiografía , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hidrazonas/síntesis química , Isoproterenol/toxicidad , Masculino , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/diagnóstico , Miocardio/patología , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
Several uncontrolled studies have encouraged the use of rituximab (RTX) in patients with myositis. Unfortunately, the first placebo-phase trial to assess the efficacy of RTX in refractory myositis did not show a significant difference between the two treatment groups, and doubts have been expressed about its study design. In this review we present an up-to-date overview of the reported experiences of RTX therapy in myositis. A PubMed search was performed to find all the available cases of refractory myositis patients treated with RTX up to July 2015. The following terms were assessed: inflammatory myopathies OR anti-synthetase syndrome OR polymyositis OR dermatomyositis AND RTX. A total of 48 studies were included. We identified 458 patients with myositis treated with RTX. We found a rate of response to RTX of 78.3%. RTX can play a role in the management of patients with myositis, at least in those with positive myositis-specific autoantibodies.
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Antirreumáticos/uso terapéutico , Miositis/tratamiento farmacológico , Rituximab/uso terapéutico , Anticuerpos Antinucleares/inmunología , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/inmunología , Humanos , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/inmunología , Miositis/inmunología , Polimiositis/tratamiento farmacológico , Polimiositis/inmunología , Resultado del TratamientoRESUMEN
The present study aimed to investigate the cardioprotective effect of hydroxytyrosol (HT) against isoproterenol-induced myocardial infarction in rats. Male rats were randomly divided into four groups, control, isoproterenol (Isop) and pretreated animals with HT in two different doses (2 and 5 mg/kg) orally for 7 days and intoxicated with isoproterenol (Isop + HT1) and (Isop + HT2) groups. Myocardial infarction in rats was induced subcutaneously by isoproterenol (100 mg/kg, s.c.) at an interval of 24 h on 6th and 7th day. On 8th day, electrocardiographic (ECG) pattern, gravimetric and biochemical parameters were assessed. Isoproterenol exhibited changes in ECG pattern, including significant ST-segment elevation and increase in the serum troponin-T level by 317 % as compared to control rats. Moreover, cardiac injury markers (creatine kinase-MB, lactate dehydrogenase, alanine aminotransferase) underwent a notable rise in serum of infarcted animals. Else, a disturbance in lipids profile and significant increase in lipase and angiotensin-converting enzyme (ACE) activities and heart weight ratio were observed in isoproterenol group. However, pre- and co-treatment with HT (2 and 5 mg/kg) improved the myocardium injury, restored the hemodynamic function and inhibited the ACE activity that prevent cardiac hypertrophy and remodeling. Overall, these findings demonstrated that HT exerted a potent cardioprotective effect against isoproterenol-induced myocardial infarction.
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Cardiotónicos/uso terapéutico , Isoproterenol/toxicidad , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/prevención & control , Alcohol Feniletílico/análogos & derivados , Remodelación Ventricular/efectos de los fármacos , Animales , Cardiotónicos/farmacología , Masculino , Infarto del Miocardio/patología , Alcohol Feniletílico/farmacología , Alcohol Feniletílico/uso terapéutico , Ratas , Ratas Wistar , Remodelación Ventricular/fisiologíaRESUMEN
CONTEXT: Zygophyllum album L. (Zygophyllaceae), commonly known as Bougriba, is widely used to treat diabetes, digestive tract spasm, and hypertension in folk medicine, in Tunisia. OBJECTIVE: This study investigates the antidiabetic, antidiarrheal, and antihypertensive activities of the leaves of the essential oil from Zygophyllum album (OZA) in alloxan-induced diabetic rats. MATERIALS AND METHODS: The oil was obtained by hydrodistillation and analyzed by GC-MS. Males rats were divided into four groups: control, diabetic-untreated group, diabetic-treated group with acarbose (10 mg/kg), and diabetic-treated rats with OZA (200 mg/kg) for 30 d. RESULTS: At the end of the experimental period, the OZA significantly decreased the activity of α-amylase in pancreas and serum of the diabetic rats by 43% and 38%, respectively, which led to reduce the serum glucose level by 60% and lower of glycated hemoglobin (HbA1c) rate by 17% as compared with untreated diabetic animals. Moreover, the OZA treatment attenuated symptoms of diarrhea, improved lipid disorders, and hypertension through inhibiting the pancreatic lipase and angiotensin-converting enzyme (ACE) activities by 47% and 25%, respectively, in serum of diabetic rats. CONCLUSION: OZA showed a good effect in the management of diabetes mellitus and exerted preventive action from related hypertension.
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Aloxano , Antidiarreicos/farmacología , Antihipertensivos/farmacología , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Experimental/tratamiento farmacológico , Inhibidores Enzimáticos/farmacología , Hipoglucemiantes/farmacología , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Antidiarreicos/aislamiento & purificación , Antihipertensivos/aislamiento & purificación , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Cromatografía Liquida , Complicaciones de la Diabetes/sangre , Complicaciones de la Diabetes/enzimología , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/enzimología , Digestión/efectos de los fármacos , Inhibidores Enzimáticos/aislamiento & purificación , Cromatografía de Gases y Espectrometría de Masas , Hemoglobina Glucada/metabolismo , Hipoglucemiantes/aislamiento & purificación , Masculino , Aceites Volátiles/aislamiento & purificación , Páncreas/efectos de los fármacos , Páncreas/enzimología , Fitoterapia , Hojas de la Planta , Aceites de Plantas/aislamiento & purificación , Plantas Medicinales , Ratas Wistar , Factores de Tiempo , Zygophyllum/química , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/sangreRESUMEN
This study aimed to evaluate the antithrombotic, anti-inflammatory and anti-cardiac remodeling properties of eugenol in isoproterenol-induced myocardial infarction in rats. Male Wistar rats were randomly divided into four groups, control, iso [100 mg/kg body weight was injected subcutaneously into rats at an interval of 24 h for 2 days (6th and 7th day) to induce MI] and pretreated animals with clopidogrel (0.2 mg/kg) and eugenol (50 mg/kg) orally for 7 days and intoxicated with isoproterenol (Iso + Clop) and (Iso + EG) groups. Isoproterenol-induced myocardial infarcted rats showed notable changes in the ECG pattern, increase in heart weight index, deterioration in the hemodynamic function and rise in plasma level of troponin-T, CK-MB and LDH and ALT by 316, 74, 172 and 45 %, respectively, with histological myocardium necrosis and cells inflammatory infiltration. In addition, significant increases in plasma levels of inflammatory biomarkers such as fibrinogen, α1, α2, ß1, ß2 and γ globulins with decrease level of albumin were observed in infarcted rats as compared to normal ones. Else, the angiotensin-converting enzyme (ACE) activity in plasma, kidney and heart of the isoproterenol-induced rats was significantly increased by 34, 47 and 93 %, respectively, as compared to normal group. However, the administration of eugenol induced a clear improvement in cardiac biomarkers injury, reduced inflammatory mediators proteins, increased heart activities of superoxide dismutase and glutathione peroxidase with reduce in thiobarbituric acid-reactive substances content and inhibition of ventricular remodeling process through inhibition of ACE activity. Overall, eugenol evidences high preventive effects from cardiac remodeling process.
Asunto(s)
Antiinflamatorios/farmacología , Coagulación Sanguínea/efectos de los fármacos , Citocinas/sangre , Eugenol/farmacología , Fibrinolíticos/farmacología , Mediadores de Inflamación/sangre , Isoproterenol , Infarto del Miocardio/tratamiento farmacológico , Miocardio/metabolismo , Remodelación Ventricular/efectos de los fármacos , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Antioxidantes/farmacología , Biomarcadores/sangre , Modelos Animales de Enfermedad , Fibrinógeno/metabolismo , Hemodinámica/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Infarto del Miocardio/sangre , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/fisiopatología , Miocardio/patología , Necrosis , Estrés Oxidativo/efectos de los fármacos , Peptidil-Dipeptidasa A/metabolismo , Ratas Wistar , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
OBJECTIVE: Myocardial infarction remains the major cause of global death due to cardiovascular diseases. This study aimed to assess the protective role of oleuropein in attenuating the cardiac remodeling in isoproterenol-induced myocardial infarction in rats. METHODS AND RESULTS: Male Wistar rats were randomly divided into four groups, control, isoproterenol (Isop) and pretreated animals with oleuropein at two different doses (20 and 40 mg/kg) orally for 7 days and intoxicated with isoproterenol (Isop+Oleu20) and (Isop+Oleu40) groups. The subcutaneous injection of isoproterenol (100 mg/kg body weight) to untreated rats for two consecutive days showed significant increases in ST-segment elevation, heart weight index and alteration in the ECG pattern and hemodynamic function. Else, serum levels of cardiac troponin-T, creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) underwent a notable rise in serum of Isop group by (345, 82, 73 and 106%, respectively) as compared to normal rats. Isoproterenol-induced myocardial injury was evidenced by alteration in serum lipids profile and increased activities of pancreatic lipase by 94% and angiotensin-converting enzyme (ACE) by 78% which reflects the occurrence of cardiac remodeling process. The histopathological findings of the infarcted group showed myocardium necrosis and cells inflammatory infiltration. However, the treatment with oleuropein gave a good protection of the myocardium by decreasing cardiac injury markers specially troponin-T, restoring hemodynamic parameters and attenuating cardiac remodeling process through inhibition of ACE activity. CONCLUSION: Oleuropein offers high preventive effects from cardiac remodeling process in rats with acute myocardial infarction.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Iridoides/uso terapéutico , Infarto del Miocardio/patología , Infarto del Miocardio/prevención & control , Vasodilatadores/uso terapéutico , Remodelación Ventricular/efectos de los fármacos , Agonistas Adrenérgicos beta , Animales , Relación Dosis-Respuesta a Droga , Electrocardiografía/efectos de los fármacos , Pruebas de Función Cardíaca , Hemodinámica/efectos de los fármacos , Glucósidos Iridoides , Iridoides/aislamiento & purificación , Isoproterenol , Masculino , Infarto del Miocardio/inducido químicamente , Olea/química , Raíces de Plantas/química , Ratas , Ratas WistarRESUMEN
The present study was designed to evaluate the cardioprotective effect of Tunisian flaxseed oil (Linum usitatissimum) against isoproterenol-induced myocardial infarction in rats by studying hypertensive and cardiac damage markers especially electrocardiographic changes and troponin T serum level. In vitro, the extracted oil showed an important inhibition of angiotensin converting enzyme (ACE) with an IC50 = 85.96 µg/ml. According to chemical analysis, this extract is composed essentially of alpha linolenic acid (ALA), an n-3 polyunsaturated fatty acid (58.59 %). Male rats were randomly divided into three groups, namely control (C), isoproterenol (ISO), and isoproterenol-treated group with flaxseed oil (FO + ISO). Isoproterenol injection showed changes in ECG pattern, including ST-segment elevation (diagnostic of myocardial infarction), increase in the serum levels of Troponin T and cardiac injury markers (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT)). However, Linum oil pre-co-treatment prevented almost all the parameters isoproterenol-induced myocardial infarction in rats. Results of the present study proved that flaxseed oil has a significant effect by heart protection against isoproterenol-induced myocardial infarction through beneficial effect of the important fraction of ALA.