RESUMO
Excessive nitric oxide (NO) causes extensive damage to the nervous system, and the adrenergic system is disordered in many neuropsychiatric diseases. However, the role of the adrenergic system in protection of the nervous system against sodium nitroprusside (SNP) injury remains unclear. In this study, we investigated the effect of ganoderic acid A (GA A) against SNP injury in neural cells and the role of adrenergic receptors in GA A neuroprotection. We found that SNP (0.125-2 mM) dose-dependently decreased the viability of both SH-SY5Y and PC12 cells and markedly increased NO contents. Pretreatment with GA A (10 µM) significantly attenuated SNP-induced cytotoxicity and NO increase in SH-SY5Y cells, but not in PC12 cells. Furthermore, pretreatment with GA A caused significantly higher adrenaline content in SH-SY5Y cells than in PC12 cells. In order to elucidate the mechanism of GA A-protecting SH-SY5Y cells, we added adrenaline, phentolamine, metoprolol, or ICI 118551 1 h before GA A was added to the culture medium. We found that addition of adrenaline (10 µM) significantly improved GA A protection in PC12 cells. The addition of ß1-adrenergic receptor antagonist metoprolol (10 µM) or ß2-adrenergic receptor antagonist ICI 118551 (0.1 µM) blocked the protective effect of GA A, whereas the addition of α-adrenergic receptor antagonist phentolamine (0.1 µM) did not affect GA A protection in SH-SY5Y cells. These results suggest that ß-adrenergic receptors play an important role in the protection of GA A in SH-SY5Y cells against SNP injuries, and excessive adrenaline system activation caused great damage to the nervous system.
Assuntos
Ácidos Heptanoicos/farmacologia , Lanosterol/análogos & derivados , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/antagonistas & inibidores , Receptores Adrenérgicos beta/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ácidos Heptanoicos/química , Humanos , Lanosterol/química , Lanosterol/farmacologia , Conformação Molecular , Fármacos Neuroprotetores/química , Óxido Nítrico/metabolismo , Nitroprussiato/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
OBJECTIVE: Intussusception secondary to pathologic lead points (PLPs) is a challenging condition for pediatric surgeons, and few studies have been published on this subject. The aim of this study was to review and analyze clinical data on the diagnosis and management of intussusception secondary to PLPs in children. METHODS: Between 2002 and 2016, a total of 65 pediatric patients with a diagnosis of intussusception secondary to PLPs were retrospectively reviewed. RESULTS: The series comprised 47 males and 18 females. The average age of the patients was 4.9 years old. All patients had typical clinical manifestations, and intussusception was proven by ultrasound. Fifty-one patients had recurrent intussusception, of whom 21 had one, 14 had two, 10 had three, and 6 had more than three. There were 20 episodes of recurrence within 24 h (39.2%), 15 episodes were found between 24 and 72 h (29.4%), and the remaining 31.4% (16/51) of recurrences occurred after 72 h. All patients received surgical intussusception reduction. Meanwhile, enterectomy was the procedure of choice in 55 patients, polypectomy in 5 patients, and cystectomy in 3 patients. The types of intussusception secondary to PLPs included small intestinal (n = 25), ileocolic (n = 19), ileocecal (n = 11), ileo-ileocolic (n = 9) and cecalcolic (n = 1). The types of PLPs included Meckel diverticulum (n = 32), intestinal duplication (n = 14), benign polyps (n = 5), malignant lymphoma (n = 4), Peutz-Jeghers syndrome (n = 3), mesenteric cyst (n = 3), intestinal wall hematoma of hemophilia (n = 2), allergic purpura (n = 1), and hamartoma (n = 1). All patients recovered well with no relapse during follow-up, except for one patient who had an intestinal obstruction from adhesions that occurred approximately 3 months after discharge and who was curable after conservative treatment. CONCLUSIONS: Intussusception secondary to PLPs tends to exhibit recurrence. There are various types of intussusception secondary to PLPs. It is necessary to improve auxiliary examinations to identify the etiology and avoid intraoperative omission. Surgical reduction of intussusception secondary to PLPs is the preferred clinical management.
Assuntos
Intussuscepção/etiologia , Intussuscepção/cirurgia , Criança , Pré-Escolar , Doenças do Sistema Digestório/complicações , Feminino , Humanos , Vasculite por IgA/complicações , Lactente , Pólipos Intestinais/complicações , Intussuscepção/diagnóstico , Masculino , Recidiva , Estudos Retrospectivos , UltrassonografiaRESUMO
Quercetin, a flavonoid present in many plants, is reported to be effective in models of neurodegenerative diseases. The aim of the present study was to evaluate the anti-tremor effects of quercetin in 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease. In rats, quercetin had no effect on apomorphine-induced rotations, but it could significantly attenuate muscle tremor of 6-OHDA lesioned rats. Interestingly, quercetin could decrease the burst frequency in a dose- and time-dependent manner. These results suggest that quercetin may have a protective effect on models to mimic muscle tremors of Parkinson's disease. This effect of quercetin may be associated with serotonergic system, but further study is needed.
Assuntos
Fármacos Neuroprotetores/farmacologia , Oxidopamina/farmacologia , Quercetina/farmacologia , Tremor/tratamento farmacológico , Animais , Apomorfina/farmacologia , Corpo Estriado/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Estrutura Molecular , Doença de Parkinson/prevenção & controle , Quercetina/química , Ratos , Ratos Sprague-DawleyRESUMO
The aim of present study is to investigate the protective effects and mechanism of salvianolic acid A (SAA) on cerebral ischemia-reperfusion injury in rats. The model was established with middle cerebral artery occlusion and reperfusion (MCAO/R) with ischemia for 1.5 h and reperfusion for 24 h in adult male SD rats. After the behavior assessment, TTC assay was used to calculate the infarct volume of rat brain; the distribution of Nrf2 in nuclear and cytoplasm and expression of HO-1 were detected by Western blot. The PC12 cells injury model was established with oxygen-glucose deprivation for 6 h and reintroduction for 24 h. Cell viability was determined with MTT assay, and the expression of Nrf2 and HO-1 were detected through immunofluorescence staining. The mechanisms were investigated in PC12 cells with Nrf2 knocking down by siRNA. SAA (10 and 20 mg·kg(-1)) significantly reduced the neuronal damage in MCAO/R model, and SAA(0.5 and 5 µmol·L(-1)) increased cell viability in PC12 cells injury model. Meanwhile, the nuclear translocation of Nrf-2 and the expression of HO-1 were increased in PC12 cell and rats brain. SAA exhibited anti-cerebral ischemia- reperfusion effects. The mechanism may be related to activation of Nrf2/HO-1 signaling pathway, which promotes the synthesis and nuclear translocation of Nrf2 to enhance the expression of the antioxidant protein HO-1.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Ácidos Cafeicos/farmacologia , Heme Oxigenase (Desciclizante)/metabolismo , Lactatos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Infarto da Artéria Cerebral Média , Masculino , Estresse Oxidativo , Células PC12 , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
BACKGROUND: Increasing studies have shown that dyslipidemia and inflammatory responses play important roles in the progression of microvascular diabetic complications. Esculin (ES), a coumarin derivative, was extracted from Fraxinus rhynchophylla. The present study was to evaluate the potential effects of ES on lipid metabolism, inflammation responses and renal damage in streptozotocin (STZ)-induced experimental diabetic rats and explore the possible mechanism. METHODS: Diabetic rat model was established by administration high-glucose-fat diet and intraperitoneal injection of STZ 45 mg/kg. ES was administrated to diabetic rats intragastrically at 10, 30 and 90 mg/kg for 10 weeks respectively. The levels of triglycerides (TG), total cholesterol (T-CHO), low density lipoproteins (LDL), and high-density-cholesterol (HDL-C) in serum were measured. IL-1, IL-6, ICAM-1, NO, NAGL, and AGEs level in serum were detected by ELISA assay. The accumulation of AGEs in kidney tissue was examined by immunohistochemistry assay. RESULTS: The results showed that ES could decrease TG, T-CHO, LDL levels in serum of diabetic rats in a dose dependent manner. ES also decreased IL-1, IL-6, ICAM-1, NO and NGAL levels in serum of diabetic rats in a dose dependent manner. Furthermore, ES at 30 and 90 mg/kg significantly decreased AGEs level in serum and alleviated AGEs accumulation in renal in diabetic rats. CONCLUSIONS: Our findings indicate that ES could improve dyslipidemia, inflammation responses, renal damage in STZ-induced diabetic rats and the possible mechanism might be associated with the inhibition of AGEs formation.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Dislipidemias/tratamento farmacológico , Esculina/administração & dosagem , Fraxinus/química , Animais , Glicemia/metabolismo , Colesterol/sangue , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/imunologia , Nefropatias Diabéticas/metabolismo , Dislipidemias/genética , Dislipidemias/imunologia , Dislipidemias/metabolismo , Humanos , Molécula 1 de Adesão Intercelular , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Ratos , Estreptozocina/efeitos adversos , Triglicerídeos/sangueRESUMO
Dexmedetomidine (DEX) a type of the anaesthetic that has been widely used in anaesthesia and intensive care. However, whether DEX affects the pharmacokinetics of drugs remains elusive. As hepatic Pglycoprotein (Pgp) serves a critical role in the disposition of drugs, the present study aimed to address whether Pgp function could be affected by DEX in vitro. In the present study, L02 cells (a normal human liver cell line) were exposed to DEX for 24 h and Pgp function was evaluated by the intracellular accumulation of Rhodamine 123. The results indicated that Pgp function was significantly impaired by DEX treatment and that the mRNA levels and protein levels of Pgp were downregulated in a dose and timedependent manner. Importantly, DEXinduced downregulation of Pgp was associated with adenosine 5'monophosphate-activated protein kinase (AMPK) activation, as it was significantly attenuated by AMPK inhibition using dorsomorphin. Furthermore, the results revealed that changes in the subcellular localisation of nuclear factor (NF)κB following AMPK activation were involved in the Pgp regulation in response to DEX treatment. Collectively, these results suggested that DEX impairs P-glycoproteinmediated efflux function in L02 cells via the AMPK/NFκB pathway, which provided direct evidence that the hepatic disposition of drugs may be affected by DEX through the downregulation of Pgp.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Dexmedetomidina/farmacologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Relação Dose-Resposta a Droga , Perfilação da Expressão Gênica , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Modelos BiológicosRESUMO
Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier (BBB) through matrix metallopeptidase 9 (MMP-9) inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion (MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg·kg-1. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.
Assuntos
Anti-Inflamatórios/administração & dosagem , Barreira Hematoencefálica/enzimologia , Isquemia Encefálica/tratamento farmacológico , Ácidos Cafeicos/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Lactatos/administração & dosagem , Metaloproteinase 9 da Matriz/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Salvia miltiorrhiza/química , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/imunologia , Encéfalo , Isquemia Encefálica/enzimologia , Isquemia Encefálica/genética , Humanos , Masculino , Metaloproteinase 9 da Matriz/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/imunologia , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/imunologiaRESUMO
Two new alkaloids, brachystemidines F (1) and G (2), were isolated from the roots of Brachystemma calycinum. Their structures were established on the basis of detailed spectroscopic analyses, including extensive NMR and HR-MS techniques. Compound 2, which exhibits an unusual N-hydroxydiazenyl (HO-N=N) moiety, is a potent immunosuppressive agent, as demonstrated by inhibition of mouse T- and B-lymphocyte proliferation, with IC50 values of 6.33 and 5.60 microg/ml, resp.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Caryophyllaceae/química , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Alcaloides/isolamento & purificação , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Estrutura MolecularRESUMO
OBJECTIVE: To categorize the patterns of abnormalities in exercise (201)TI myocardial scintigraphy and explore the mechanisms. METHODS: Exercise (201)TI myocardial scintigraphy was performed in 203 patients with clinically suspected coronary artery disease, including 74 normotensive patients, 78 hypertensive patients without left ventricle hypertrophy (LVH) and 51 hypertensive patients with LVH. All the patients underwent coronary angiography one month before or after (201)TI myocardial scintigraphy, and the patterns of abnormal findings were categorized as segmental, non-segmental and mixed patterns. Patients with abnormal (201)TI myocardial perfusion and normal coronary angiographic findings were followed up. RESULTS: In hypertensive patients without and with LVH, the ratios of abnormal perfusion in segmental, non-segmental and mixed types were 52/60 and 32/58, 4/60 and 9/58, and 4/60 and 17/58, respectively. The ratios of normal coronary angiography in the 3 types were 17/84, 13/13 and 10/21, respectively. Among the 40 patients followed up, 5 with segmental abnormality and 2 with mixed abnormalities developed large coronary artery disease, which was found in none of the patients with segmental abnormality. CONCLUSIONS: In hypertensive patients with and without LVH, segmental perfusion abnormalities may be attributed to the anatomic and functional stenosis of the large coronary arteries, and the non-segmental abnormal perfusion might be only possible with coronary microvascular diseases.
Assuntos
Doença das Coronárias/diagnóstico por imagem , Teste de Esforço , Radioisótopos de Tálio , Doença das Coronárias/complicações , Teste de Esforço/métodos , Feminino , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Angiografia Cintilográfica/métodos , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
OBJECTIVE: To assess the possibility of replacing neck phantom with a stand to support the irradiation source in thyroid radioiodine uptake test. METHODS: The counts per minute (cpm) of 9 radioiodine samples of step-wise increasing irradiation doses were measured when different placements of the irradiation source, namely via neck wax phantom, a supporting stand or direct fixation, were adopted, with the uniform distance between the standard source and the crystal surface of the detector being 26 cm. In clinical trial, the values of radioactive iodine uptake (RAIU) of 30 patients with hyperthyroidism were obtained adopting 3 and 24 h separately after oral radioactive iodine administration both neck phantom method and stand-supported standard source measurement, and statistical analysis of the results were performed. RESULTS: Statistical analysis revealed significant differences between the cpm measured using the 3 methods (F=59.339, P=0.000), and that measured by neck wax phantom was 16% higher than those obtained from measurements using a stand (P=0.000) or direct fixation (P=0.000). Despite that no significant difference was noted between the latter 2 methods (P=0.324), the 3 approaches were closely correlated with each other. The results of RAIU obtained by stand-supported source placement were significantly higher than those from neck phantom approach (t=26.033, P=0.000), showing close correlation between them (r=0.996, P=0.000) that could be expressed as RAIUnp=0.863xRAIUst. CONCLUSION: The results of RAIU from the 2 approaches of source placement methods are significantly different but highly correlated, and the 2 methods are not equal but mutual replacement is possible when some technical treatment of the results is made.
Assuntos
Radioisótopos do Iodo/farmacocinética , Pescoço , Glândula Tireoide/metabolismo , Humanos , Hipertireoidismo/radioterapia , Radioisótopos do Iodo/uso terapêutico , Imagens de Fantasmas , Dosagem Radioterapêutica , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the value of (99m)Tc-N-NOET(NOET) myocardial perfusion imaging during exercise in the diagnosis of coronary artery disease (CAD), and the relationship between exercise NOET lung/heart ratio and left ventricular diastolic function. METHODS: Exercise-delayed NOET myocardial perfusion imaging was performed in 49 patients undergoing coronary angiography, among whom 29 had coronary stenosis>or=50% and 20 normal coronary artery. RESULTS: The sensitivity and specificity of exercise NOET myocardial perfusion imaging were 86.2% and 95.0%, respectively, in the detection of CAD. The NOET lung/heart ratio of CAD patients with multiple branch involvement (0.76+/-0.13) was significantly higher than those of patients with single branch lesion (0.62+/-0.06) and with normal coronary artery (0.58+/-0.13, F=18.04, P=0.002- 0.001). When the lung/heart ratio was over 0.70, the sensitivity and specificity of the imaging for detecting the presence of multiple branch involvement were 93.5% and 83.3%, respectively. NOET lung/heart ratio showed a significant correlation with E/A ratio (r=-0.771, P<0.000 1). CONCLUSION: Exercise NOET lung/heart ratios has diagnostic values for multiple branch lesions and left ventricular diastolic function abnormalities in patients with CAD.
Assuntos
Doença das Coronárias/diagnóstico por imagem , Coração/diagnóstico por imagem , Compostos de Organotecnécio , Tiocarbamatos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Teste de Esforço , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Cintilografia , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To investigate the relation of 5 major risk factors (hypertension, diabetes, hyperlipidemia, overweight, smoking) of coronary artery disease (CAD) to the findings from thallium-201 single photon emission computed tomography. METHODS: Exercise 201TI myocardial scintigraphy was performed in 346 patients with clinically suspected CAD, who were divided into no risk, low risk, moderate risk, and high risk groups, based on CAD risk scores. RESULTS: The rate of thallium-201 perfusion abnormalities in no risk, low risk, moderate risk, and high risk groups were 48.1%, 70.6%, 89% and 100%, respectively, showing significant difference between them (X2=49.6, P=0.000 1). In patients with CAD risk factors, significant relation was found between the risk scores and semiquantitative scores, lung-to-heart ratios or segment abnormalities (0.133 r 0.450, 0.000 1 P 0.031). CONCLUSION: A close relation between CAD risk factors and thallium-201 myocardial scintigraphy is found. Routine thallium-201 myocardial scintigraphy should be performed in patients clinically suspected of coronary artery disease with CAD risk factors, especially those with moderate to high risk factors.
Assuntos
Doença das Coronárias/epidemiologia , Fatores de Risco , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença das Coronárias/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioisótopos de Tálio , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
OBJECTIVE: To evaluate the application of heparin lithium as anticoagulant in in vitro tests of thyroid function. METHODS: The blood samples obtained by venipuncture from 32 subjects (including 10 normal subjects and 22 patients with thyroid disorder) were collected in parallel dry vacuum tubes with one of them containing heparin lithium, for assay of TSH, FT3, FT4 by chemoluminescence immunoassay. RESULTS: No difference was found in TSH and FT4 levels determined separately from the parallel tubes (TSH: t=1.846, P=0.075; FT4: t=1.649, P=0.110) with closely correlated results (TSH: r=1.000, P=0.000; FT4: r=0.999, P=0.000), and the clinical diagnoses therefrom derived were perfectly matched. FT3 level in ordinary dry vacuum tubes, however, was significantly higher than that in the tube containing heparin lithium (t=-6.253, P=0.000), but still close correlation was observed between them (r=0.999, P=0.000 0). Inconsistent clinical decisions occurred in 7 of the 32 subjects in respect of FT3 levels respectively assayed in the 2 tubes, but when the normal ranges of FT3 level were established for the 2 tubes separately, the same clinical diagnoses were reached. CONCLUSION: TSH and FT4 levels as determined in the 2 tubes are comparable, and even though FT3 levels does not present this feature, close relation is obvious and therefore the 2 values can be equivalent after establishment of their respective normal limits or after linear regression processing.
Assuntos
Anticoagulantes/farmacologia , Heparina/análogos & derivados , Heparina/farmacologia , Lítio/farmacologia , Doenças da Glândula Tireoide/metabolismo , Tireotropina/análise , Heparina/química , Humanos , Lítio/química , Testes de Função TireóideaRESUMO
OBJECTIVE: To investigate the changes in 99mTc and 131I uptake in patients with Grave's disease after intake of iodine-containing food. METGIDSl The 3-hour and 24-hour radioactive iodine uptake (RAIU) and 99mTc uptake ratio (TI) were measured and the thyroid weight (TW) was estimated in 20 patients with Graves' disease both before and after restraint of iodine-containing diet. RESULTS: Significant difference was found in RAIU and TI in patients after restraint of iodine-rich diet (Z=3.920, P=0.000 for 3-hour RAIU and Z=3.920, P=0.000 for 24-hour RAIU; Z=2.199, P=0.028 for TI and Z=3.920, P=0.000 for TW estimated from 99mTc images). The tendency in such changes was significantly different (Z=4.066, P=0.000 for RAIU and TI; Z=4.243, P=0.000 for RAIU and TW). After restraint of iodine-rich food, RAIU of 3-hour and 24-hour increased in all the patients, and TI decreased in 16, remained the same level in 2 and increased in 2 patients; TW decreased in 18 and increased in 2 patients. CONCLUSION: Iodine-containing food has different effects on thyroid 131I and 99mTc uptakes, which decreases 131I uptake in all the patients and increases 99mTc in 90% of them.
Assuntos
Doença de Graves/metabolismo , Radioisótopos do Iodo/farmacocinética , Iodo/administração & dosagem , Pertecnetato Tc 99m de Sódio/farmacocinética , Glândula Tireoide/metabolismo , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função TireóideaRESUMO
OBJECTIVE: To evaluate the myocardial perfusion in hypertensive patients with and without left ventricular hypertrophy using thallium-201 (201TI) myocardial scintigraphy and explore the mechanism that causes the perfusion abnormalities. METHODS: Thallium-201 myocardial scintigraphy was performed in 85 patients with clinically suspected coronary artery disease to assess the myocardial perfusion status. For patients with myocardial perfusion abnormalities as indicated by the scintigraphy, coronary angiography was ordered within 1 month. RESULTS: The incidence of 201TI myocardial perfusion abnormalities in hypertensive patients with ventricular hypertrophy (85.7%) was significantly higher than that in the normotensive (39.3%, P<0.01) and hypertensive patients not complicated with hypertrophy (61.2%, P<0.05). The semiquantitative score was higher in the hypertensive patients with hypertrophy than in the normotensive (P<0.01) and hypertensive patients without hypertrophy (P<0.05). More hypertensive patients with hypertrophy (9/18) had normal results of coronary angiography than the normotensive (0/13, P=0.044) and hypertensive patients without hypertrophy did (3/19, P<0.05). CONCLUSIONS: A higher rate of 201TI perfusion abnormalities occurs in the hypertensive patients with ventricular hypertrophy, which may be attributed to the pathological changes in the major coronary vessels and to the coronary microvascular diseases as well.
RESUMO
AIMS: The aim of the present study is to evaluate the effects of baicalein on the 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinsonian tremor and elucidate the potential mechanism. MAIN METHODS: Adult male Sprague-Dawley rats were subjected to Parkinsonian tremor by 6-OHDA-medial forebrain bundle (MFB) injection. Baicalein (100, 200 and 400mg/kg) was administrated by gavage once daily, for 1 week. The anti-tremor effect of baicalein on a model of Parkinsonian tremor was examined. Dopamine (DA), glutamate (GLu) and gamma-aminobutyric acid (GABA) levels in basal ganglia were determined by HPLC-ECD. Cytochrome oxidase subunit I (COI) mRNA expression in subthalamic nucleus (STN) was assessed by real-time RT-PCR. GABA transaminase (GABA-T) and glutamine synthetase (GS) protein expression in basal ganglia were tested by immunostaining. Effects of baicalein on [Ca(2+)]i induced by GLu were tested in primary cultured mesencephalic neurons. KEY FINDINGS: Baicalein significantly attenuated muscle tremor of PD rats. The metabolic balance between GLu and GABA was modulated by baicalein treatment. It was found that treatment with baicalein inhibited the STN's COI mRNA expression in experimental PD. In rat primary mesencephalic cultures, baicalein inhibited significantly GLu-induced intracellular calcium [Ca(2+)]i increase. SIGNIFICANCE: These results suggest that baicalein plays a neuromodulatory role in balancing GABA and GLu neurotransmitter in basal ganglia, and might be a promising candidate for the treatment of tremor-dominant type of idiopathic Parkinson's disease.
Assuntos
Antiparkinsonianos/uso terapêutico , Flavanonas/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Antiparkinsonianos/farmacologia , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Cálculos da Dosagem de Medicamento , Flavanonas/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Estrutura Molecular , Reação em Cadeia da Polimerase , Ratos , Ratos Sprague-DawleyRESUMO
Baicalein is one of the major flavonoids obtained from the Scutellaria root. Previous pharmacological studies found that baicalein had neuroprotective effects in animal models of Parkinson's disease. The purpose of this paper was to explore the molecular mechanism of the action of baicalein on PC12 cells and isolated rat brain mitochondria. Firstly, we investigated the effects of baicalein on rotenone-induced toxicity in PC12 cells. The results showed that baicalein suppressed rotenone-induced apoptosis, and inhibited the accumulation of reactive oxidant species, ATP deficiency, mitochondrial membrane potential dissipation, and caspase-3/7 activation in a concentration-dependent manner, indicating that baicalein likely improved mitochondrial function. Furthermore, we used isolated rat brain mitochondria to evaluate the effect of baicalein. Treatment with baicalein prevented rotenone-induced reactive oxidant species production, ATP deficiency and mitochondrial swelling in isolated brain mitochondria. Interestingly, exposure of isolated mitochondria to baicalein promoted mitochondrial active respiration. These results suggest that baicalein may be a mitochondria-targeted antioxidant and exerts neuroprotective effects on rotenone-induced neurotoxicity. This study supports our previous research that baicalein possesses neuroprotective activity in vivo and it is worthy of further study.
Assuntos
Encéfalo/citologia , Citoproteção/efeitos dos fármacos , Flavanonas/farmacologia , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Neurotoxinas/toxicidade , Rotenona/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 7/metabolismo , Respiração Celular/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Dilatação Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Ratos Sprague-DawleyRESUMO
Many studies of Parkinson's disease suggest that oxidative stress is involved in the neurodegenerative process. Baicalein has been shown to have antioxidant effects. The present study examines the effect of baicalein on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in C57BL/6 mice. MPTP treatment impaired spontaneous motor activity and rotarod performance, but baicalein improved this deficit. Moreover, baicalein at 280 and 560 mg/kg exhibited a protective effect against the MPTP-induced decrease in tyrosine hydroxylase (TH)-positive fibers in the substantia nigra, demonstrated by the immunohistological, morphological and behavioral outcomes. MPTP treatment also decreased dopamine levels in the striatum. However, treatment with baicalein attenuated these decreases in dopamine levels by changing dopamine catabolism and inhibiting dopamine turnover. The neuroprotective effect of baicalein on dopaminergic neurons may partly be due to its antioxidant properties. Therefore, we speculate that baicalein might be a promising candidate for prevention or treatment of oxidative stress-related neurodegenerative disorders such as Parkinson's disease.
Assuntos
Encéfalo/efeitos dos fármacos , Flavanonas/farmacologia , Intoxicação por MPTP/prevenção & controle , Animais , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/fisiopatologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Dopamina/metabolismo , Glutationa Peroxidase/metabolismo , Intoxicação por MPTP/fisiopatologia , Intoxicação por MPTP/psicologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Substância Negra/efeitos dos fármacos , Substância Negra/enzimologia , Substância Negra/patologia , Superóxido Dismutase/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: BAIMAI-SAN prescription is a famous Chinese minority complex prescription used for curing neuropathy. MATERIALS AND METHODS: The Effective Compounds Groups of BAIMAI-SAN (ECGBM) is determined by high through-put screening, and it includes picroside II, verbascose, taurine and ellagic acid and borneol. To research the potential protective effect of ECGBM on the function of peripheral neuropathy, diabetic rats with peripheral neuropathy were induced by streptozotocin and treated with ECGBM (0.1, 0.3, 0.9 mg/kg/day i.g.) for 75 days. Primary cortical neuronal cultures were subjected to high d-glucitol, and treated with ECGBM prophylactically. RESULTS: The administration resulted in reductions in speed of sciatic motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV) and response speed to pain in the sciatic nerve fiber. Data from primary cortical neuronal cultures experiments indicated that neuronal survival rates were increased, and LDH release was decreased and the loss of neurite length was alleviated in ECGBM group. CONCLUSIONS: It is first report that ECGBM could protect the peripheral neuron in diabetic rat in vivo and in vitro. This activity may be associated with the neuron protective effect.
Assuntos
Complicações do Diabetes/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Condução Nervosa/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Fitoterapia , Animais , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Membro Posterior , L-Lactato Desidrogenase/metabolismo , Masculino , Medicina Tradicional , Mongólia , Condução Nervosa/fisiologia , Neuritos/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Neurônios/fisiologia , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/farmacologia , Dor/etiologia , Dor/fisiopatologia , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Plantas Medicinais , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiopatologia , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/fisiologia , SorbitolRESUMO
Processes of synaptic plasticity, such as long-term potentiation (LTP), has been considered a cellular correlate of learning and memory and many neurological disorders accompanied by cognitive deficits exhibit abnormal synaptic function. This emerging concept is exemplified by Alzheimer's disease. Mounting evidence suggests that Alzheimer's disease begins with subtle alterations of hippocampal synaptic efficacy prior to frank neuronal degeneration, which make it critical to identify LTP enhancers to slow down or stop the progression of Alzheimer's disease. In this study, we found flavonoid luteolin could enhance basal synaptic transmission and facilitate the induction of LTP by high frequency stimulation in the dental gyrus of rat hippocampus. Furthermore, we investigated the effects of luteolin on chronic cerebral hypoperfusion-induced spatial learning dysfunction and LTP impairment in rat. The results showed chronic cerebral hypoperfusion produced by 2-vessel occlusion significantly impaired spatial learning and memory, and luteolin reversed the learning and memory deficit. 2-vessel occlusion resulted in dramatic inhibition of LTP formation in the hippocampus and luteolin significantly rescued the LTP impairment. These results demonstrate that luteolin not only directly modulates LTP formation, but also protects synapses from the detrimental effects of chronic cerebral hypoperfusion on LTP formation, which may contribute to the protective effects of luteolin on learning and memory. By immunoblotting, we found the effects of luteolin on LTP and memory may due to the activation of cAMP response element-binding protein (CREB). Therefore, flavonoid luteolin shows great potential as a novel treatment agent for protecting synaptic function and enhancing memory in neurodegenerative disorders.