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BACKGROUND: The aim of the current study is to assess the prevalence of different categories of thyroid dysfunction and their associated risk factors among the modern urban population of Tehran, the capital of Iran. METHODS: The present investigation is a sub-study of the HAMRAH study, a population-based prospective study designed to assess the prevalence of traditional cardiovascular risk factors and their changes through a 10-year follow-up. 2228 (61% female) adults aged between 30 and 75 years old and with no overt cardiovascular diseases were selected through a multistage cluster randomized sampling. Blood levels of thyroid-stimulating hormone (TSH), thyroxin (T4), and triiodothyronine (T3) were measured with the aim of assessing the prevalence of abnormal thyroid function status among the modern urban Iranian population, and in order to report the total prevalence of participants with clinical hypo- or hyperthyroidism, the number of individuals taking thyroid-related drugs were added to the ones with overt thyroid dysfunction. A subgroup analysis was also performed to determine the associated risk factors of thyroid dysfunction. RESULTS: The prevalence of thyroid dysfunction among the total population was 7% (95%CI: 5.9 - 8%) and 0.4% (95% CI: 0.1 - 0.6%) for subclinical and overt hypothyroidism, and 1.6% (95% CI: 1 - 2%) and 0.2% (95% CI: 0 - 0.3%) for subclinical and overt hyperthyroidism, respectively. Clinical thyroid dysfunction was detected in 10.3% of the study population (9.4% had clinical hypo- and 0.9% had clinical hyperthyroidism). In the subgroup analysis, thyroid dysfunction was significantly more prevalent among the female participants (P-value = 0.029). CONCLUSIONS: In the current study, the prevalence of different categories of abnormal thyroid status, and also the rate of clinical hypo- and hyperthyroidism was assessed using the data collected from the first phase of the HAMRAH Study. In this study, we detected a higher prevalence of clinical and subclinical hypothyroidism among the Iranian population compared to the previous studies.
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Hipertiroidismo , Hipotiroidismo , Enfermedades de la Tiroides , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Estudios Prospectivos , Prevalencia , Irán/epidemiología , Enfermedades de la Tiroides/epidemiología , Hipertiroidismo/epidemiología , Tiroxina , TirotropinaRESUMEN
Background: To evaluate the efficiency of Menstrual blood Stromal/Stem Cells (MenSCs) administration in Myocardial Infarction (MI), the effects of MenSCs and their derived conditioned Medium (CM) on cardiac function in MI rat model was assessed. Methods: Animals were divided into four groups including sham group, MI group, MenSCs derived CM group (CM group), and MenSCs suspended in CM (MenSCs+CM) group. The injection of different groups was carried out 30 min after ligation of left anterior descending coronary artery into the infarct border zone. Results: The results showed a significant reduction in scar size after injection of MenSCs+CM compared to MI group. Ejection fraction and fractional shortening of MenSCs+CM group were higher than CM and MI group at day 28. Administration of MenSCs+CM led to much more survival of cardiomyocytes, and prevention of meta-plastic development. Moreover, human mitochondrial transfer from MenSCs to cardiomyocytes was seen in group treated by MenSCs+CM. Indeed, MenSCs+CM treatment evoked nuclear factor-κB (NF-κB) down-regulation more than other treatments. Conclusion: MenSCs+CM treatment could significantly ameliorate cardiac function by different mechanisms including inhibition of cartilaginous metaplasia, inhibition of NF-κB and mitochondrial transfer.
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BACKGROUND: Patients' rights are integral to medical ethics. This study aimed to perform sentiment analysis and opinion mining on patients' messages by a combination of lexicon-based and machine learning methods to identify positive or negative comments and to determine the different ward and staff names mentioned in patients' messages. METHODS: The level of satisfaction and observance of the rights of 250 service recipients of the hospital was evaluated through the related checklists by the evaluator. In total, 822 Persian messages, composed of 540 negative and 282 positive comments, were collected and labeled by the evaluator. Pre-processing was performed on the messages and followed by 2 feature vectors which were extracted from the messages, including the term frequency-inverse document frequency (TFIDF) vector and a combination of the multifeature (MF) (a lexicon-based method) and TFIDF (MF + TFIDF) vectors. Six feature selectors and 5 classifiers were used in this study. For the evaluations, 5-fold cross-validation with different metrics including area under the receiver operating characteristic curve (AUC), accuracy (ACC), F1 score, sensitivity (SEN), specificity (SPE) and Precision-Recall Curves (PRC) were reported. Message tag detection, which featured different hospital wards and identified staff names mentioned in the study patients' messages, was implemented by the lexicon-based method. RESULTS: The best classifier was Multinomial Naïve Bayes in combination with MF + TFIDF feature vector and SelectFromModel (SFM) feature selection (ACC = 0.89 ± 0.03, AUC = 0.87 ± 0.03, F1 = 0.92 ± 0.03, SEN = 0.93 ± 0.04, and SPE = 0.82 ± 0.02, PRC-AUC = 0.97). Two methods of assessment by the evaluator and artificial intelligence as well as survey systems were compared. CONCLUSION: Our results demonstrated that the lexicon-based method, in combination with machine learning classifiers, could extract sentiments in patients' comments and classify them into positive and negative categories. We also developed an online survey system to analyze patients' satisfaction in different wards and to remove conventional assessments by the evaluator.
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Inteligencia Artificial , Satisfacción del Paciente , Humanos , Teorema de Bayes , Aprendizaje Automático , Curva ROCRESUMEN
Cardiomyopathies comprise a heterogeneous group of cardiac diseases identified by myocardium disorders and diminished cardiac function. They often lead to heart failure or heart transplantation and constitute one of the principal causes of morbidity and mortality worldwide. Circular RNAs (circRNAs) are a novel type of noncoding RNAs. They are covalently closed and single-stranded and derived from the exons and introns of genes by alternative splicing. This specific structure renders them resistant to exonuclease digestion. Many recent studies have demonstrated that circRNAs are highly abundant and conserved and can play central roles in biological functions such as microRNA (miRNA) sponging, splicing, and transcription regulation. Emerging evidence indicates that circRNAs can play significant roles in cardiovascular diseases, including cardiomyopathies. In this review, we briefly describe the current understanding regarding the classification, nomenclature, characteristics, and function of circRNAs and report recent significant findings concerning the roles of circRNAs in cardiomyopathies. Furthermore, we discuss the clinical application potential of circRNAs as the therapeutic targets and diagnostic biomarkers of cardiomyopathies.
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Cardiomiopatías , MicroARNs , Empalme Alternativo , Biomarcadores , Cardiomiopatías/genética , Exonucleasas/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genéticaRESUMEN
Introduction: The autologous pericardium, treated or fresh, is used in reconstructive cardiovascular surgery. We aimed to describe the features of fresh pericardium utilized in right ventricular outflow tract (RVOT) reconstruction, years after the initial surgery. Methods: This cross-sectional study was performed on 72 patients (65.3% male, mean age =18.68 ± 9.63 y) with a history of RVOT reconstruction with the fresh autologous pericardium who underwent reoperation. During the surgery, a 1 × 1 cm sample was cut from the previous pericardial patch, and hematoxylin and eosin (H & E), Masson's trichrome, and immunohistochemistry (IHC) staining was conducted. All the stained slides were evaluated,and the descriptive results were explained. Results: The mean follow-up duration was 13.48 ± 7.38 years. In preoperative evaluations,53 (73.6%) patients exhibited no RVOT dilatation, 17 (23.6%) showed mild RVOT dilatation,and 2 (2.8%) had RVOT aneurysms. The H & E staining revealed no calcification in 80.55%(58/72), mild calcification in 9.72% (7/72), and moderate calcification in 9.72% (7/72) of the total samples. None of the specimens demonstrated a marked calcification. All the samples were positive for CD31, CD34, smooth muscle alpha-actin, and von Willebrand factor in IHC. In Masson's trichrome staining, on average, 64.74% (±18.61) of the tissue sections contained collagen fibers. Conclusion: The fresh autologous pericardium, utilized for RVOT reconstruction, showed viability, growth potential, positivity for endothelial cell markers, vascular differentiation,insignificant calcification, and no stenosis at long-term follow-up. We would, therefore, suggest it as a suitable choice for such reconstructive operations. Moreover, its usage during total correction of tetralogy of Fallot could be safe, feasible, and durable.
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BACKGROUND: We sought to estimate the prevalence of diabetes mellitus (DM) and pre-DM and their associated factors among a sample of the Iranian urban population between 2017 and 2019. METHODS: The present investigation is a sub-study on the HAMRAH cohort study, a longitudinal population-based cohort study to assess the 10-year risk of cardiovascular diseases and their related risk factors in the adult population of the Iranian capital, Tehran. Via a multistage cluster randomized sampling method, 2123 adults aged between 30 and 75 years who had no history of cardiovascular diseases were selected for the study. With the aid of the 2010 American Diabetes Association criteria for the definition of DM and pre-DM, age and sex-specific prevalence rates were estimated. RESULTS: The estimated overall prevalence of DM was 14.3% (95% CI: 13.1%-15.8%): 10.4% known DM (95% CI: 9.1%-11.8%) and 4% newly diagnosed DM (95% CI: 3.1%-5.1%). Pre-DM was detected in about 29.2% of the study participants (95% CI: 22.9-36.3%). Our logistic regression analysis revealed that increasing age, higher systolic blood pressure, higher levels of triglycerides, and lower levels of high-density lipoprotein were significantly associated with DM. CONCLUSIONS: DM and pre-DM follow a notable incremental pattern among the Iranian urban population. This finding underscores the significance of the need to improve prevention and screening strategies in the Iranian urban population.
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Diabetes Mellitus , Estado Prediabético , Adulto , Anciano , Estudios de Cohortes , Estudios Transversales , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Femenino , Humanos , Irán/epidemiología , Masculino , Persona de Mediana Edad , Estado Prediabético/diagnóstico , Estado Prediabético/epidemiología , Prevalencia , Factores de Riesgo , Población UrbanaRESUMEN
Hypoplastic right ventricle is a rare congenital disease usually associated with pulmonary atresia or tricuspid atresia. Isolated right ventricular hypoplasia is a rare anomaly without important valvular abnormalities. It is associated with inter atrial septal defects leading to the right-to-left shunting of blood. Patients with isolated right ventricular hypoplasia usually have different and variable courses. In some patients, it is recognized in the perinatal period and necessitates prompt intervention; nonetheless, there are some reports of this anomaly in old age with no significant symptoms. In this report, we describe the clinical data and management of 6 adult cases with isolated right ventricular hypoplasia treated medically or surgically based on the severity of the disease and symptoms and then offer an in-depth discussion regarding this rare anomaly.
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MicroRNAs (miRNAs) are a subfamily of small noncoding RNAs that play a variety of roles in regulating gene expression in nearly all organisms. They affect different biological pathways by post-transcriptionally regulating mRNAs. Aside from miRNAs' role in maintaining cellular homeostasis, their perturbation is related to several pathologic states and diseases. Cardiovascular disorders are considered some of the most mortal multifactorial diseases that are caused by the deregulation of network of genes and effects of environmental factors. In this review, we discuss the role of miRNAs in cardiac homeostasis and malfunctions. We reviewed published research on association and role of miRNAs in cardiac development and diseases and investigated the possible links between regulatory miRNAs and different cardiac disorders. Research shows that manipulating miRNAs expression affects the integrity and functionality of the cardiovascular system. Moreover, deregulation of miRNAs, is observed in many cardiac diseases. These findings intensify the pivotal role of miRNAs in the development and speciï¬c pathological disorders of the cardiovascular system. In this review, we summarized the latest findings on the involvement of miRNAs in cardiac development, and continued by their role in congenital heart diseases and rheumatic heart disease, which are some of the leading causes of infant death and cardiovascular morbidity and mortality. Considering the significance of miRNAs in cardiac homeostasis and malfunctions, they are considered as promising therapeutic targets in cardiovascular diseases.
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Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Although in recent years there has been a significant progress in the diagnosis, treatment, and prognosis of CVD, but due to their complex pathobiology, developing novel biomarkers and therapeutic interventions are still in need. MicroRNAs (miRNAs) are a fraction of non-coding RNAs that act as micro-regulators of gene expression. Mounting evidences over the last decade confirmed that microRNAs were deregulated in several CVDs and manipulating their expression could affect homeostasis, differentiation, and function of cardiovascular system. Here, we review the current knowledge concerning the roles of miRNAs in cardiovascular diseases with more details on cardiac remodeling, arrhythmias, and atherosclerosis. In addition, we discuss the latest findings on the potential therapeutic applications of miRNAs in cardiovascular diseases.
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Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/genética , MicroARNs/genética , Animales , Biomarcadores , Enfermedades Cardiovasculares/tratamiento farmacológico , Regulación de la Expresión Génica , Humanos , MicroARNs/uso terapéutico , PronósticoRESUMEN
BACKGROUND: Inflammatory is one of the main cause of aortic valve stenosis (AS), so discovering novel biomarkers for the targeted therapy of inflammation could be an attractive strategy in AS prevention. The objectives of our study were to clarify the modulatory role of resistin and silent information regulator 1 (SIRT1) before and after surgery and also to evaluate the therapeutic effects of resveratrol. METHODS: Nineteen AS patients and 15 healthy subjects were studied as the case and control groups, respectively. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured to determine the levels of resistin and SIRT1 and the effects of resveratrol on them. RESULTS: Significant increase in resistin expression was observed in the patients compare to the control (p ≤0.01), and this upregulation was augmented 72 h following surgery (p ≤0.01). The SIRT1 expression decreased in the AS group compare to the control but this reduction was not significant. Aortic valve replacement caused a higher decrease in the protein (p ≤0.01) and mRNA level (p ≤0.05) of SIRT1. Resveratrol in the AS group significantly diminished the resistin level (p ≤0.05) but increased the SIRT1 level (p ≤0.001). CONCLUSIONS: In our patients with AS, the resistin level was increased, whereas the expression of SIRT1 was reduced and surgery augmented these alterations. Resveratrol improved inflammation in the PBMCs of the patients through the SIRT1/resistin pathway. These findings suggest that pharmacological therapy with resveratrol might be a novel approach to alleviating inflammation in patients with AS.
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Estenosis de la Válvula Aórtica/terapia , Inhibidores Enzimáticos/uso terapéutico , Resistina/metabolismo , Resveratrol/uso terapéutico , Sirtuina 1/metabolismo , Adulto , Anciano , Animales , Biomarcadores/análisis , Femenino , Humanos , Inflamación/metabolismo , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Estilbenos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Chronic morphine (CM) treatment increases the phosphorylation of the mammalian target of rapamycin (mTOR), which confers neuroprotection against ischemia/reperfusion (I/R) injury. Besides its important regulatory role in the proliferation, metabolism, and survival of cells, the mTOR is critically involved in intracellular signaling events during I/R injury. In the present study, we investigated the interaction between the expressions of the mTOR and inducible nitric oxide synthase (iNOS) and their possible protective effects on hippocampal neurons against I/R injury in morphine-dependent mice. Additive doses of morphine were administered for 5 days to BALB/c mice so as to induce CM preconditioning before I/R injury. Global brain ischemia was induced via the occlusion of bilateral common carotid arteries for 30 min. CM attenuated iNOS expression, NO production, and malondialdehyde activity in the hippocampal tissue. Pretreatment with rapamycin, the inhibitor of mTOR, abolished all the above mentioned effects of CM. These findings suggested that CM acted through the mTOR signaling pathways to regulate iNOS expression and oxidative state in the hippocampal tissue after I/R injury.
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The signaling pathway of chronic morphine treatment to prevent neuronal damage following transient cerebral ischemia is not clear. In this study, we examined the role of mammalian target of rapamycin (mTOR) to identify the neuroprotective effects of chronic morphine preconditioning on the hippocampus following ischemia-reperfusion (I/R) injury. Morphine was administered for 5 days, twice a day, before inducing I/R injury. The possible role of mTOR was evaluated by the injection of rapamycin (5 mg/kg body weight, by intraperitoneal injection) before I/R was induced. The passive avoidance test was used to evaluate memory performance. Neuronal density and apoptosis were measured in the CA1 region, 72 h after I/R injury. The expressions of mTOR and phosphorylated mTOR (p-mTOR), as well as superoxide dismutase (SOD) activity were determined 24 h after I/R injury. Chronic morphine treatment attenuated apoptosis and neuronal loss in the hippocampus after I/R injury, which led to improvement in memory (P < 0.05 vs. untreated I/R) and increase in the expression of p-mTOR (P < 0.05 vs. untreated I/R) and SOD activity (P < 0.05 vs. untreated I/R) in the hippocampus. Pretreatment with rapamycin abolished all the above-mentioned protective effects. These results describe novel findings whereby chronic morphine preconditioning in hippocampal CA1 neurons is mediated by the mTOR pathway, and through increased phosphorylation of mTOR can alleviate oxidative stress and apoptosis, and eventually protect the hippocampus from I/R injury.
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Región CA1 Hipocampal/patología , Morfina/farmacología , Neuronas/patología , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/patología , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Animales , Apoptosis/efectos de los fármacos , Reacción de Prevención/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Ratones Endogámicos BALB C , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fosforilación/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
PURPOSE: Pharmacologic preconditioning, through activating several mechanisms and mediators, can increase the tolerance of different tissues against ischemia/reperfusion (I/R) injury. Recent studies have shown that morphine preconditioning has protective effects in different organs, especially in the heart. Nevertheless, its mechanisms are not well elucidated in the brain. The present study aimed to clarify whether the activation of mitochondrial KATP (mKATP) channels in chronic morphine (CM) preconditioning could decrease hippocampus damage following I/R injury. MATERIALS AND METHODS: CM preconditioning was performed by the administration of additive doses of morphine for 5days before I/R injury induction. I/R injury was induced by the occlusion of bilateral common carotid arteries. The possible role of mKATP channels was evaluated by the injection of 5-hydroxydecanoate (5-HD) before I/R injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was performed to detect apoptosis in hippocampal neurons. The expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (BAX) and levels of malondialdehyde (MDA) and catalase (CAT) enzymes were assessed. RESULTS: CM attenuated apoptosis in the hippocampal CA1 neurons (P<0.001 vs I/R), and mKATP channel blocking with 5-HD significantly increased apoptosis (P<0.001 vs CM+I/R). CM increased CAT activity (P<0.05 vs I/R) and Bcl-2 protein expression (P<0.01 vs I/R), while it decreased MDA level (P<0.05 vs I/R) and BAX protein expression (P<0.05 vs I/R). Pretreatment with 5-HD abolished all the above-mentioned effects of CM. CONCLUSIONS: These findings describe novel evidence whereby CM preconditioning in hippocampal CA1 neurons can improve oxidative stress and apoptosis through the activation of mKATP channels and eventually protect the hippocampal tissue against I/R injury.
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Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Región CA1 Hipocampal/patología , Morfina/farmacología , Neuronas/patología , Neuroprotección/efectos de los fármacos , Canales de Potasio/metabolismo , Animales , Apoptosis/efectos de los fármacos , Catalasa/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Neuronas/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
An impaired ability to regulate microglia activation by fractalkine (CX3CL1) leads to microglia chronic sub-activation. How this condition affects outcome after acute brain injury is still debated, with studies showing contrasting results depending on the timing and the brain pathology. Here, we investigated the early and delayed consequences of fractalkine receptor (CX3CR1) deletion on neurological outcome and on the phenotypical features of the myeloid cells present in the lesions of mice with traumatic brain injury (TBI). Wild type (WT) and CX3CR1(-/-) C57Bl/6 mice were subjected to sham or controlled cortical impact brain injury. Outcome was assessed at 4 days and 5 weeks after TBI by neuroscore, neuronal count, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Compared with WT mice, CX3CR1(-/-) TBI mice showed a significant reduction of sensorimotor deficits and lower cellular damage in the injured cortex 4 days post-TBI. Conversely, at 5 weeks, they showed a worsening of sensorimotor deficits and pericontusional cell death. Microglia (M) and macrophage (µ) activation and polarization were assessed by quantitative immunohistochemistry for CD11b, CD68, Ym1, and inducible nitric oxide synthase (iNOS)-markers of M/µ activation, phagocytosis, M2, and M1 phenotypes, respectively. Morphological analysis revealed a decreased area and perimeter of CD11b(+) cells in CX3CR1(-/-) mice at 4 days post-TBI, whereas, at 5 weeks, both parameters were significantly higher, compared with WT mice. At 4 days, CX3CR1(-/-) mice showed significantly decreased CD68 and iNOS immunoreactivity, while at 5 weeks post-injury, they showed a selective increase of iNOS. Gene expression on CD11b(+) sorted cells revealed an increase of interleukin 10 and insulin-like growth factor 1 (IGF1) at 1 day and a decrease of IGF1 4 days and 5 weeks post-TBI in CX3CR1(-/-), compared with WT mice. These data show an early protection followed by a chronic exacerbation of TBI outcome in the absence of CX3CR1. Thus, longitudinal effects of myeloid cell manipulation at different stages of pathology should be investigated to understand how and when their modulation may offer therapeutic chances.
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Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/fisiopatología , Receptor 1 de Quimiocinas CX3C/fisiología , Progresión de la Enfermedad , Activación de Macrófagos , Microglía/metabolismo , Animales , Receptor 1 de Quimiocinas CX3C/deficiencia , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Factores Protectores , Factores de TiempoRESUMEN
OBJECTIVES: Morphine dependence (MD) potently protects heart against ischemia reperfusion (IR) injury through specific signaling mechanisms, which are different from the pathways involved in acute morphine treatment or classical preconditioning. Since opioid receptor density changes post cerebral ischemia strongly correlated with brain histological damage, in the present study, we tried to elucidate the possible role of opioid receptors in IR injury among morphine-dependent mice. MATERIALS AND METHODS: Accordingly, incremental doses (10 mg/kg/day to 30 mg/kg/day) of morphine sulphate were subcutaneously administered for 5 days before global brain ischemia induction through bilateral common carotid artery occlusion. Animals were received naloxone (5 mg/kg) or L-NAME (20 mg/kg) 30 min after the last morphine dose. Twenty four hr after the ischemia induction, Retention trial of passive avoidance test and western blot analysis were done. histological analysis (TUNEL and NISSL staining) performed 72 hr after ischemia. RESULTS: MD improved post ischemia memory performance (P<0.01) and neuronal survival (P<0.001) and decreased apoptosis (P<0.05) in region I of hippocampus (CA1 region) in mouse. Treatment with naloxone or L-NAME abolished all MD aforementioned effects. CONCLUSION: Results of the present study suggested that opioid receptors activation in the early hr post ischemia is crucial for MD-induced hippocampus tolerance against IR injury. Opioid receptor-dependent balance of NO production was another key factor in MD-induced protection. Further studies are required to determine the effect of MD on opioid receptor changes after ischemia and its correlation with MD-induced protection.
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Different signaling pathways are involved in tissue protection against ischemia reperfusion (IR) injury, among them mammalian target of rapamycin (mTOR) and related pathways have been examined in many recent studies. Present study evaluated the role of mTOR in remote ischemic preconditioning (RIPC) of hippocampus. Renal ischemia was induced (3 cycles of 5min occlusion and 5min reperfusion of unilateral renal artery) 24h before global brain ischemia (20min bilateral common carotid artery occlusion). Saline or rapamycin (mTOR inhibitor; 5mg/kg, i.p.) was injected 30min before RIPC. mTOR and phosphorylated mTOR (p-mTOR) expression, superoxide dismutase (SOD) activity and retention trial of passive avoidance test were determined 24h after global ischemia. Apoptosis and neuronal cell density were assessed 72h after hippocampal ischemia. RIPC decreased apoptosis (p<0.05 vs. IR), improved memory (p<0.05 vs. IR), and augmented p-mTOR expression and SOD activity after hippocampal ischemia (p<0.05 vs. IR). Rapamycin abolished all protective effects of RIPC (p<0.05 vs. RIPC+IR) suggesting a role for mTOR in RIPC induced hippocampal protection.
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Isquemia Encefálica/metabolismo , Hipocampo/irrigación sanguínea , Hipocampo/metabolismo , Precondicionamiento Isquémico , Serina-Treonina Quinasas TOR/metabolismo , Animales , Western Blotting , Modelos Animales de Enfermedad , Etiquetado Corte-Fin in Situ , Masculino , Ratones , Ratones Endogámicos BALB C , FosforilaciónRESUMEN
The aim of present study was to investigate the effect of onion (Allium cepa) peel hydroalcoholic extract (OPE) on rat hypertension induced by high-fructose diet and aorta contractility. The OPE was prepared by maceration method using 70% ethanol. The thoracic aorta from male adult rat (Wistar) was dissected and suspended in Krebs-Henseleit solution under 1 g resting tension. Tissue preparation was contracted by KCl (80 mM) or phenylephrine (Phe, 1 microM) and then the extract was applied cumulatively (0.0625-2 mg mL(-1)). Hypertension was induced in negative control and three groups of rats by adding fructose (10% WN/V) in drinking water for 6 weeks but control group received tap water. Hypertensive groups received saline or OPE at 200, 400 and 800 mg kg(-1) daily for last 3 weeks by gavage. Results showed that OPE reduces aorta contractions induced by KCl or Phe in a concentration-dependent manner (p < 0.001). Removing aorta endothelium did not attenuate the OPE activity. Inhibition of nitric oxide, cGMP and prostaglandin synthesis by L-NAME (100 microM), methylene blue (10 microM) and indomethacin (10 microM), respectively, did not attenuate OPE activity. Atropine abolished ACh-induced relaxation in Phe precontracted aorta but not the OPE-induced relaxation. Although the extract did not change heart rate but after 3 weeks reduced the hypertension induced by fructose (p < 0.001). Present results indicated that OPE reduces aortic contractions possibly via inhibition of calcium influx but without involving NO, cGMP, endothelium and prostaglandins. The OPE hypotensive effect could be due to extract quercetin content, antioxidant activity and inhibiting vascular smooth muscle cells Ca2+ influx.