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1.
Rev. Esc. Enferm. USP ; 53: e03487, Jan.-Dez. 2019. tab, graf
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1020392

RESUMO

RESUMO Objetivo Avaliar o efeito da Justicia acuminatissima , Sara Tudo do Amazonas, na função renal, na hemodinâmica renal, no perfil oxidativo e na histologia renal em ratos com injúria renal aguda isquêmica. Método Ensaio pré-clínico com ratos Wistar, adultos, machos (250-350 g), distribuídos nos grupos Sham, Isquemia e Isquemia + Sara Tudo. Foram avaliados os parâmetros hemodinâmicos, a função renal, o estresse oxidativo e a histologia renal. Resultados O pré-tratamento com o Sara Tudo atenuou a lesão funcional, o que foi evidenciado pelo aumento no clearance de creatinina, redução dos marcadores oxidativos e elevação de tióis, pela melhora significativa do fluxo sanguíneo renal, diminuição da resistência vascular renal e redução da lesão tubulointersticial no tecido renal. Conclusão A renoproteção da Justicia acuminatissima , Sara Tudo, na injúria renal aguda isquêmica, caracterizou-se por melhora significativa da função renal, reduzindo a lesão oxidativa, com impacto positivo na histologia renal.


RESUMEN Objetivo Evaluar el efecto de la planta Justicia acuminatissima , "Sana Todo del Amazonas", en la función renal, la hemodinámica renal, el perfil oxidativo y la histología renal en ratones con injuria renal aguda isquémica. Método Ensayo pre clínico con ratones Wistar, adultos, machos (250-350 g), distribuidos en los grupos Sham, Isquemia e Isquemia + Sana Todo. Fueron evaluados los parámetros hemodinámicos, la función renal, el estrés oxidativo y la histología renal. Resultados El pre tratamiento con el Sana Todo atenuó la lesión funcional, lo que fue evidenciado por el aumento en el aclaramiento de creatinina, reducción de los marcadores oxidativos y elevación de tioles, por la mejora significativa del flujo sanguíneo renal, disminución de la resistencia vascular renal y reducción de la lesión tubulointersticial en el tejido renal. Conclusión La renoprotección de la Justicia acuminatissima , "Sana Todo del Amazonas", en la injuria renal aguda isquémica se caracterizó por mejora significativa de la función renal, reduciendo la lesión oxidativa, con impacto positivo en la histología renal.


ABSTRACT Objective To evaluate the effects of Justicia acuminatissima , or Amazonian Sara Tudo , on renal hemodynamics, oxidative profile, and renal histology in rats with ischemic acute kidney injury. Method Preclinical assay with adult male Wistar rats, weighing from 250 g to 350 g, distributed into Sham, ischemia, and ischemia + Sara Tudo groups. Hemodynamic parameters, renal function, oxidative stress, and renal histology were evaluated. Results Pretreatment with Sara Tudo reduced the functional injury, which was shown by the increase in creatinine clearance and thiols; reduction of oxidative markers, renal vascular resistance, and tubulointerstitial injury in the renal tissue; and the significant improvement in renal blood flow. Conclusion The renoprotection provided by Justicia acuminatissima , or Sara Tudo , in cases of ischemic acute kidney injury was characterized by a marked improvement in renal function, reducing the oxidative injury, and impacting on renal histology positively.


Assuntos
Ratos , Reperfusão , Medicamentos Fitoterápicos , Lesão Renal Aguda , Terapias Complementares , Ratos Wistar , Experimentação Animal
2.
Int Heart J ; 60(5): 1176-1183, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564708

RESUMO

Recently, the potential role of gut microbiome (GM) in cardiovascular diseases has been revealed. Heart failure (HF) is one of the most prevalent cardiovascular diseases worldwide; however, whether GM dysbiosis participates in the development of HF remains largely unknown. This study aimed to investigate the specific changes in GM composition and function in isoproterenol (ISO)-induced HF in rats.The rats were divided into C (control), 4w-HF (ISO, 2.5 mg/kg/day for 4 weeks, intraperitoneally), and 2w-HF (ISO, 2.5 mg/kg/day for 2 weeks, intraperitoneally) groups. The cardiac structure and function in rats were assessed, and metagenomic analyses were then performed. Compared with the healthy control group, we found that the Shannon diversity index and microbial gene count in the 4w-HF and 2w-HF groups was drastically decreased. High-throughput sequencing showed that the three groups differed in intestinal bacterial community composition. Overgrowth of bacteria, such as Prevotella, was observed in the 4w-HF group, with reduced growth of bacteria, such as Roseburia, Lactobacillus, and Butyrivibrio, associated with healthy status compared with the C group on the genus level. Concomitant with the alteration of GM composition, underrepresentation of health-linked microbial function was observed in both the 4w-HF and 2w-HF groups compared with the C group.Iso-induced HF rats showed a significant decrease in the diversity and richness of the intestinal microbiome, with a downregulation of the key intestinal bacterial groups and overgrowth of bacteria considered to be involved in inflammatory responses as well as a decrease in health-linked microbial function. Our data indicated that altered GM may be a potential player in the pathogenesis and progression of HF.


Assuntos
Bactérias/classificação , Microbioma Gastrointestinal/efeitos dos fármacos , Insuficiência Cardíaca/microbiologia , Isoproterenol/efeitos adversos , Metagenômica/métodos , Animais , Bactérias/genética , Modelos Animais de Doenças , Ecocardiografia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico por imagem , Sequenciamento de Nucleotídeos em Larga Escala , Injeções Intraperitoneais , Isoproterenol/farmacologia , Masculino , Filogenia , Ratos , Análise de Sequência de DNA
3.
Biol Res ; 52(1): 54, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581950

RESUMO

BACKGROUND: IcarisideII (ICAII) could promote the differentiation of adipose tissue-derived stem cells (ADSCs) to Schwann cells (SCs), leading to improvement of erectile function (EF) and providing a realistic therapeutic option for the treatment of erectile dysfunction (ED). However, the underlying molecular mechanisms of ADSCs and ICAII in this process remain largely unclear. METHODS: ADSCs were treated with different concentrations of ICAII. Cell proliferation was determined by MTT assay. qRT-PCR and western blot were performed to detect expressions of SCs markers, signal transducer and activator of transcription-3 (STAT3), and microRNA-let-7i (let-7i). Luciferase reporter assay was conducted to verify the regulatory relationship between let-7i and STAT3. The detection of intracavernosal pressure (ICP) and the ratio of ICP/mean arterial pressure (MAP) were used to evaluate the EF in bilateral cavernous nerve injury (BCNI) rat models. RESULTS: ICAII promoted cell proliferation of ADSCs in a dose-dependent manner. The mRNA and protein levels of SCs markers were increased by ICAII treatment in a dose-dependent manner in ADSCs. Moreover, let-7i was significantly decreased in ICAII-treated ADSCs and upregulation of let-7i attenuated ICAII-induced promotion of SCs markers. In addition, STAT3 was a direct target of let-7i and upregulated in ICAII-treated ADSCs. Interestingly, overexpression of STAT3 abated the let-7i-mediated inhibition effect on differentiation of ADSCs to SCs and rescued the ICAII-mediated promotion effect on it. Besides, combination treatment of ADSCs and ICAII preserved the EF of BCNI rat models, which was undermined by let-7i overexpression. CONCLUSION: ICAII was effective for preserving EF by promoting the differentiation of ADSCs to SCs via modulating let-7i/STAT3 pathway.


Assuntos
Tecido Adiposo/citologia , Diferenciação Celular/efeitos dos fármacos , Disfunção Erétil/tratamento farmacológico , Flavonoides/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células de Schwann/efeitos dos fármacos , Animais , Western Blotting , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Transfecção
4.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(3): 285-290, 2019 Jul 26.
Artigo em Chinês | MEDLINE | ID: mdl-31544408

RESUMO

OBJECTIVE: To investigate the pathogenicity of Pneumocystis and its association with the development of chronic obstructive pulmonary disease (COPD). METHODS: The rat model of Pneumocystis pneumonia (PCP) was induced by intraperitoneal injection with dexamethasone, which was confirmed by pathogenic detection. The pathologic changes of rat lung specimens were examined using conventional HE staining, and the expression of inflammatory cells were detected by flow cytometry in bron-choalveolar lavage fluid (BALF) and splenic tissues of the rat model of PCP. In addition, the serum levels of matrix metalloproteinase 8 (MMP-8) and MMP-9 were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Fusion and atrophy of alveolar spaces and hyperplasia of lung tissue were seen in the lung specimens of the rat model of PCP, and foam-like alveolar exudates and infiltration of inflammation cells were observed in the alveolar space, while severe infections exhibited consolidation of lung, which was similar to pathological features of COPD. The counts of CD8+ T lymphocytes (t = -7.920 and -12.514, P < 0.01), macrophages (t = -7.651 and -14.590, P < 0.01) and granulocytes (t = -10.310 and -16.578, P < 0.01) significantly increased and the counts of CD4+ T lymphocytes (t = 6.427 and 18.579, P < 0.01) significantly reduced in the BALF and splenic specimens of the rats with PCP relative to those without PCP. In addition, higher serum MMP-8 (t = -8.689, P < 0.01) and MMP-9 levels (t = -7.041, P < 0.01) were measured in rats with PCP than in those without PCP. CONCLUSIONS: Pneumocystis infection may be associated with the development and progression of COPD.


Assuntos
Pneumocystis , Pneumonia por Pneumocystis , Doença Pulmonar Obstrutiva Crônica/etiologia , Animais , Líquido da Lavagem Broncoalveolar/microbiologia , Modelos Animais de Doenças , Pulmão/microbiologia , Pneumocystis/patogenicidade , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/microbiologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Ratos , Virulência
5.
Auris Nasus Larynx ; 46(6): 957, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31472921
6.
Bol. latinoam. Caribe plantas med. aromát ; 18(5): 459-479, sept. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1008268

RESUMO

Neuronal cell damage is often caused by prolonged misuse of Methylphenidate (MPH). Topiramate (TPM) carries neuroprotective properties but its assumed mechanism remains unclear. The present study evaluates in vivo role of various doses of TPM and its mechanism against MPH-induced motor activity and related behavior disorder. Thus, we used domoic acid (DOM), bicuculline (BIC), Ketamine (KET), Yohimibine (YOH) and Haloperidole (HAL) as AMPA/kainite, GABAA, NMDA, ɑ2 adrenergic and D2 of dopamine receptor antagonists respectively. Open Field Test (OFT), Elevated Plus Maze (EPM) and Forced Swim Test (FST) were used to study motor activity, anxiety and depression level. TPM (100 and 120 mg/kg) reduced MPH-induced rise and inhibited MPH-induced promotion in motor activity disturbance, anxiety and depression. Pretreatment of animals with KET, HAL, YOH and BIC inhibited TPM- improves anxiety and depression through the interacting with Dopaminergic, GABAA, NMDA and ɑ2-adrenergic receptors.


El daño a las células neuronales a menudo es causado por el uso prolongado de metilfenidato (MPH). El topiramato (TPM) tiene propiedades neuroprotectoras, pero su mecanismo de acción no es claro. El presente estudio evalúa el papel in vivo de varias dosis de TPM y su mecanismo contra la actividad motora inducida por MPH y el trastorno de comportamiento relacionado. Utilizamos ácido domoico (DOM), bicuculina (BIC), ketamina (KET), yohimbina (YOH) y haloperidol (HAL), así como antagonistas AMPA/kainato, GABAA, NMDA, ɑ2-adrenérgico y D2 dopaminérgicos, respectivamente. Se utilizaron las pruebas de campo abierto (OFT), elevación de laberinto (EPM) y natación forzada (FST) para estudiar la actividad motora, la ansiedad y el nivel de depresión. El TPM (100 y 120 mg/kg) redujo el aumento inducido por MPH e inhibió la promoción inducida por MPH en la alteración de la actividad motora, la ansiedad y la depresión. El tratamiento previo de animales con KET, HAL, YOH y BIC inhibió el TPM, mejora la ansiedad y la depresión a través de la interacción con los receptores dopaminérgicos, GABAA, NMDA y ɑ2-adrenérgico.


Assuntos
Animais , Masculino , Ratos , Comportamento Animal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , /farmacologia , Transtornos Mentais/prevenção & controle , Metilfenidato/efeitos adversos , Ratos Wistar , Neurotransmissores/metabolismo , Transtornos Mentais/induzido quimicamente , Atividade Motora/efeitos dos fármacos
7.
Bol. latinoam. Caribe plantas med. aromát ; 18(5): 504-517, sept. 2019. ilus, tab, graf
Artigo em Inglês | LILACS | ID: biblio-1008288

RESUMO

Nowdays it is established that ischemic brain damage like ischemic stroke is one of the leading cause of death and disability in the population that assumes relevance development of anti-ischemic drugs. The work studied the anti-hypoxic and anti-ischemic effect of 7 plant extracts. Antihypoxic activity was assessed on models of hypobaric, hypercapnic, histotoxic, hematotoxic hypoxia. Anti-ischemic activity of test-extracts was studied on the focal cerebral ischemia model. Administration of Tagetes patula, Gaillardia pulchella, Sorbaria sorbifolia, Grossularia reclinata, Ribes nigrum, Rubus caesius and Lysimachia punctata extracts contributed to the necrosis zone reduction by 56.6% (p<0.05); 37.3% (p<0.05); 73.2% (p<0.05); 49.4% (p<0.05); 42.5% (p<0.05); 85.5% (p<0.05); 44.2% (p<0.05) and also restored aerobic metabolism in brain tissue. Test - objects increased of the animal lifespan under hypoxia conditions. Based on the data obtained, it is assumed that further studies of North Caucasus flora plant extracts as cerebro-protective agents are promising.


Hoy en día, se ha establecido que el daño cerebral isquémico, como el accidente cerebrovascular isquémico, es una de las principales causas de muerte y discapacidad en la población lo cual hace relevante el desarrollo fármacos antiisquémicos. En este trabajo se estudió el efecto antihipóxico y antiisquémico de siete extractos de plantas. La actividad antihipóxica se evaluó en modelos de hipoxia hipocrática, hipercápnica, histotóxica y hematotóxica. La actividad antiisquémica de los extractos de prueba se estudió en el modelo de isquemia cerebral focal. La administración de los extractos de Tagetes patula; Gaillardia pulchella; Sorbaria sorbifolia; Grossularia reclinata; Ribes nigrum; Rubus caesius y Lysimachia punctata contribuyeron a la reducción de la zona de necrosis en un 56,6% (p<0,05); 37,3% (p<0,05); 73,2% (p<0,05); 49,4% (p<0,05); 42,5% (p<0,05); 85,5% (p<0,05); 44.2% (p<0.05), respectivamente, además, de restaurar el metabolismo aeróbico en el tejido cerebral. Comparado con el control, se observó un aumento en el tiempo de sobrevida del animal en condiciones de hipoxia. Sobre la base de los interesantes datos obtenidos, se sugiere estudios adicionales de extractos de plantas de la flora del Cáucaso Norte como agentes protectores del cerebro.


Assuntos
Animais , Masculino , Camundongos , Ratos , Extratos Vegetais/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Hipóxia/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Trifosfato de Adenosina/análise , Ratos Wistar , Ácido Láctico/análise , Ácido Pirúvico/análise , Camundongos Endogâmicos BALB C
8.
Braz J Med Biol Res ; 52(9): e8290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482998

RESUMO

Tendon rupture is a very frequent accident involving average people and high-performance athletes. Clinical studies describe tendon recovery as a painful and slow process involving different biochemical and histological events. Ascorbic acid (AA) is a potent antioxidant as well as an important cofactor for collagen synthesis. In the current study, we evaluated if local treatment with AA is able to promote tendon repair in tenotomized rats. Animals were submitted to Achilles tendon rupture followed by surgical suture. Control and AA groups received in loco injection of saline solution (0.9% NaCl) and 30 mM AA, respectively. Histological and functional recovery of Achilles tendon tissue was evaluated at 7, 14, and 21 days post-surgery. Hematoxylin/eosin staining and collagen fluorescence analysis showed intense disarrangement of tendon tissue in the saline group. Tenotomized animals also showed hypercellularity in tendon tissue compared with non-tenotomized animals. The Achilles functional index (AFI) showed a significant decrease of tendon functionality in tenotomized animals at 7, 14, and 21 days post-surgery. AA accelerated tissue organization and the recovery of function of the Achilles tendons. The beneficial effect of AA treatment was also observed in the organization of the collagen network. Data presented in the current work showed that in loco treatment with AA accelerated the recovery of injured Achilles tendon post-surgery.


Assuntos
Tendão do Calcâneo/efeitos dos fármacos , Ácido Ascórbico/administração & dosagem , Colágeno/efeitos dos fármacos , Traumatismos dos Tendões/cirurgia , Tendão do Calcâneo/lesões , Tendão do Calcâneo/patologia , Animais , Colágeno/fisiologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Tenotomia , Cicatrização/efeitos dos fármacos
9.
Biol Res ; 52(1): 50, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492196

RESUMO

BACKGROUND: Ureteral obstruction causes injury of the renal tissues and can irreversibly progress to renal fibrosis, with atrophy and apoptosis of tubular cells. The goal of the current study was to examine the effects of rhein on the apoptosis o renal tubular cells as well as renal fibrosis using a rodent model of unilateral ureteral obstruction (UUO). METHODS: UUO was induced through ureteral ligation, then animals received treatments with rhein or vehicle. The control rats only received sham operation. The renal tissue was harvested 1 week after surgery for assessment of kidney fibrosis. RESULTS: The expressions of collagen I and α-smooth muscle actin (α-SMA), as well as the severity of renal tubular apoptosis and fibrosis were time-dependently increased following UUO. Treatments with rhein partially inhibited such responses. Renal interstitial fibrosis was associated with STAT3 (signal transducer and activator of transcription 3) phosphorylation as well as altered expressions of Bax and Bcl2, both apoptosis-related proteins. Treatment with rhein also partly blocked these responses. CONCLUSION: These findings demonstrated that rhein mitigated apoptosis of renal tubular cell as well as renal fibrosis in a UUO rodent model. This curative effect is likely mediated via suppression of STAT3 phosphorylation.


Assuntos
Antraquinonas/administração & dosagem , Apoptose/efeitos dos fármacos , Rim/patologia , Obstrução Ureteral/prevenção & controle , Animais , Modelos Animais de Doenças , Progressão da Doença , Fibrose/metabolismo , Fibrose/patologia , Fibrose/prevenção & controle , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologia
10.
Bratisl Lek Listy ; 120(9): 650-657, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475548

RESUMO

In this contribution we present graph theoretical approach to image processing focus on biological data. We use the graph cut algorithms and extend them for obtaining segmentation of biological data. We deal with tumor brain cells and rats brain to show the existence and presence of inflammatory molecules. We introduce a completely new method for filtering of data (Tab. 3, Schema 4, Fig. 7, Ref. 13). Keywords: graph cuts, segmentation, tumore analyses of cells, computer morphometry.


Assuntos
Algoritmos , Neoplasias Encefálicas/patologia , Processamento de Imagem Assistida por Computador , Modelos Teóricos , Animais , Encéfalo/citologia , Ratos
11.
Bratisl Lek Listy ; 120(9): 703-710, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475559

RESUMO

OBJECTIVES:  The aim of our study was to describe the effect of prenatal testosterone exposure on 2D:4D in both sexes, and to determine whether this effect is mediated via the androgen receptor. In addition, the sex differences in lengths of 2D, 4D, and 2D:4D ratio were analyzed. BACKGROUND:  Clinical studies suggest a negative correlation between prenatal testosterone exposure and ratio of the lengths of the second and fourth digits (2D:4D). However, less is known about the underlying molecular mechanisms. METHODS:  Pregnant rats were treated with olive oil, testosterone, flutamide or testosterone with flutamide daily from the fourteenth day of pregnancy until delivery. The finger lengths of adult offspring were measured using both, digital scanning of the paws and µCT analysis of the phalanges. RESULTS:  None of the aforementioned methods revealed any effect of testosterone on 2D:4D. µCT measurements showed that prenatal hyperandrogenism in both sexes leads to shorter 2D compared to controls. Moreover, the testosterone treatment in males resulted in the shortening of 4D when compared to controls. CONCLUSION:  Prenatal hyperandrogenism leads to shorter lengths of 2D and 4D; however, it does not affect 2D:4D ratio. Whether other steroid hormones and/or testosterone metabolites affect the 2D:4D ratio requires further investigation (Tab. 5, Fig. 3, Ref. 32).


Assuntos
Exposição Materna , Testosterona , Dedos do Pé/anatomia & histologia , Animais , Feminino , Masculino , Gravidez , Ratos , Comportamento Sexual
13.
Rev Col Bras Cir ; 46(4): e2238, 2019 Sep 09.
Artigo em Português, Inglês | MEDLINE | ID: mdl-31508735

RESUMO

OBJECTIVE: to compare the effects of the hydroalcoholic extract from the peel of Camu-Camu, a fruit plant belonging to the Myrtaceae family, widely distributed in the Amazon basin, with those of sleeve gastrectomy, on the weight and glycemia of Wistar rats. METHODS: twenty-four Wistar rats underwent obesity induction through a hyperlipid diet for eight weeks (fat period), and were randomized into three groups: Control Group (CG), Camu-Camu Group (CCG) and Bariatric Surgery Group (BSG). After this period, all animals returned to a normal diet and the intervention period began: CG did not undergo any intervention beyond diet change; CCG animals underwent gavage procedure for administration of Camu-Camu hydroalcoholic extract, 1g/kg/day, for four weeks; and the BSG was submitted to the surgical procedure of sleeve gastrectomy. We followed all animals for four weeks. RESULTS: there was only one loss in BSG due to a gastric fistula. We observed significant variations in the animals' mean weight: the CG evolved with weight gain even after the withdraw of the hypercaloric diet, while the other two groups presented weight reduction. BSG presented a significant reduction of weight and BMI (p<0.05); CCG achieved a significant reduction only of the BMI (p<0.05). There were no statistically significant changes in the glycemic levels. CONCLUSION: in spite of reducing weight, the crude hydroalcoholic extract of the Camu-Camu peel was not able to be as efficient as sleeve gastrectomy in the control of body weight in Wistar rats.


Assuntos
Cirurgia Bariátrica , Myrtaceae/química , Obesidade/dietoterapia , Obesidade/cirurgia , Perda de Peso , Animais , Suplementos Nutricionais , Modelos Animais de Doenças , Frutas/química , Masculino , Terapia Nutricional , Obesidade/etiologia , Ratos , Ratos Wistar
14.
Fa Yi Xue Za Zhi ; 35(4): 393-395, 2019 Aug.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-31532144

RESUMO

Abstract: Objective To explore the relationship between the electrical conductivity (EC) and biochemical indicators of rat cerebrum tissues and postmortem intervals (PMIs) and discuss the mechanism of applying EC to infer PMI. Methods Forty healthy Sprague-Dawley rats were sacrificed and stored in an environment of about 25 ℃. The whole cerebrum tissues of rats were removed respectively at different PMIs of 0, 1, 2, 3, 4, 5, 6, and 7 d, and then made into homogenized impregnation solution. The EC and related biochemical indicators (potassium, sodium, chloride, calcium, inorganic phosphorus, magnesium, uric acid, urea nitrogen and creatinine) in cerebrum tissue impregnation solution were determined, and the relationships among EC in impregnation solution, related biochemical indicators and PMI were analyzed. Results The EC in cerebrum tissues increased gradually with the extension of PMI, and the content of uric acid, urea nitrogen and inorganic phosphorus in its impregnation solution also increased gradually with the extension of PMI. The correlation of EC, uric acid, urea nitrogen, and inorganic phosphorus with PMI was relatively good (R2 was 0.95-0.99), and there was a linear correlation between the content change of uric acid, urea nitrogen, inorganic phosphorus and EC (R2 was 0.97-0.99). The changes of the other 6 kinds of biochemical indicators with the extension of PMI within 7 d after the rats' death were non-significant (P>0.05). Conclusion The correlation between EC in cerebrum tissues, uric acid, urea nitrogen, inorganic phosphorus and PMI were relatively good, and combining various indicators can also improve the accuracy of PMI estimation.


Assuntos
Cérebro/patologia , Condutividade Elétrica , Mudanças Depois da Morte , Animais , Patologia Legal , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
15.
Fa Yi Xue Za Zhi ; 35(4): 411-418, 2019 Aug.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-31532148

RESUMO

Abstract: Objective To establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) rapid determination method for simultaneous analysis of 20 fentanyl-related substances in blood. Methods With fentanyl-D5 as an internal standard, the blood was extracted by liquid-liquid extraction (LLE), then separated with an ACQUITY UPLC HSS T3 chromatographic column, and finally 20 fentanyl-related substances were simultaneously analyzed with multiple reaction monitoring (MRM) mode. Results The limits of detection (LOD) of all compounds were 0.02-0.03 ng/mL, and the limits of quantitation (LOQ) were 0.05-0.2 ng/mL. Within the mass concentration range of 0.05-40 ng/mL, 20 fentanyl-related substances had a good linear relationship, and correlation coefficients were larger than 0.99. The accuracy of the method was 87.69%-114.68% and the extraction recovery rate was 85.35%-101.80%, and no significant matrix effect was observed. The established method was successfully applied to the detection of sufentanil in rat blood after sufentanil was injected. Sufentanil could still be detected in blood of rats 10 h after sufentanil injection. Conclusion The established method has the advantages of simple pretreatment, high sensitivity and good selectivity, and can be used for the determination of fentanyl-related substances in forensic toxicology analysis.


Assuntos
Cromatografia Líquida de Alta Pressão , Fentanila/sangue , Espectrometria de Massas em Tandem , Animais , Toxicologia Forense , Ratos , Reprodutibilidade dos Testes , Sufentanil/sangue
16.
Fa Yi Xue Za Zhi ; 35(4): 419-422, 2019 Aug.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-31532149

RESUMO

Abstract: Objective To develop a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of the content of 4-fluoromethamphetamine (4-FMA) in rat plasma, and to provide a methodological basis for the study of the toxicokinetics of 4-FMA in rats. Methods Rat plasma samples were added into internal standard methamphetamine (MA). Its proteins were precipitated with methanol and then separated with Poroshell 120 EC-C18 chromatographic column. A 0.1% formic acid aqueous solution and a 0.1% formic acid acetonitrile solution were used as the mobile phase at the flow rate of 0.4 mL/min. Electrospray ionization source was used for detection in the multiple reaction monitoring (MRM) mode. Results The linear relationship was good when the mass concentration of 4-FMA in plasma samples was in the range of 5-1 000 ng/mL (r>0.999). The limit of detection (LOD) was 3 ng/mL and the limit of quantification (LOQ) was 5 ng/mL. The accuracy was expressed as relative error (RE), and in the range of ±5%, the intra-day precision and inter-day precision (relative standard deviation, RSD) less than 9%, and the extraction recovery rate was more than 90%. The analysis and detection of plasma samples were completed within 2.5 min. Conclusion This study developed a HPLC-MS/MS method for the determination of 4-FMA in rat plasma samples. This method is accurate, rapid, simple and sensitive and can be applied to the study of toxicokinetics of 4-FMA.


Assuntos
Cromatografia Líquida de Alta Pressão , Metanfetamina/sangue , Espectrometria de Massas em Tandem , Animais , Limite de Detecção , Metanfetamina/análogos & derivados , Ratos , Reprodutibilidade dos Testes , Toxicocinética
17.
Adv Exp Med Biol ; 1161: 193-217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562631

RESUMO

Headache is a common complaint after mild traumatic brain injury (mTBI). Changes in the CNS lipidome were previously associated with acrolein-induced headache in rodents. mTBI caused similar headache-like symptoms in rats; therefore, we tested the hypothesis that mTBI might likewise alter the lipidome. Using a stereotaxic impactor, rats were given either a single mTBI or a series of 4 mTBIs 48 h apart. 72 h later for single mTBI and 7 days later for repeated mTBI, the trigeminal ganglia (TG), trigeminal nucleus (TNC), and cerebellum (CER) were isolated. Using HPLC/MS/MS, ~80 lipids were measured in each tissue and compared to sham controls. mTBI drove widespread alterations in lipid levels. Single mTBI increased arachidonic acid and repeated mTBI increased prostaglandins in all 3 tissue types. mTBI affected multiple TRPV agonists, including N-arachidonoyl ethanolamine (AEA), which increased in the TNC and CER after single mTBI. After repeated mTBI, AEA increased in the TG, but decreased in the TNC. Common to all tissue types in single and repeated mTBI was an increase the AEA metabolite, N-arachidonoyl glycine, a potent activator of microglial migration. Changes in the CNS lipidome associated with mTBI likely play a role in headache and in long-term neurodegenerative effects of repeated mTBI.


Assuntos
Lesões Encefálicas Traumáticas , Sistema Nervoso Central , Cefaleia , Inflamação , Lipídeos , Neoplasias , Animais , Lesões Encefálicas Traumáticas/fisiopatologia , Sistema Nervoso Central/fisiopatologia , Cefaleia/fisiopatologia , Inflamação/fisiopatologia , Lipídeos/química , Lipídeos/genética , Lipídeos/fisiologia , Neoplasias/fisiopatologia , Ratos
18.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(7): 625-630, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31537248

RESUMO

Objective To investigate the effect of homocysteine (Hcy) on the cardiomyocytes cultured in vitro, and to analyze the role of folic acid in DNA methylation to explore the protective effect and mechanism of folic acid during Hcy exposure of H9C2 cardiomyocytes. Methods H9C2 cells were treated with Hcy at different concentrations (0, 0.5, 1, 2) mmol/L for 24 hours. Cell viability was tested by CCK-8 assay. The apoptosis was detected by flow cytometry. H9C2 cells were divided into 2 mmol/L Hcy group, 0.1 mmol/L folic acid combined with 2 mmol/L Hcy group, 0.1 mmol/L folic acid group and DMSO control group. The above corresponding treatment lasted 24 hours. Then we detected the cell viability and apoptosis. The total DNA methylation level was determined by MethylFlash ELISA kit. DNMT1, DNMT3a, DNMT3b mRNA and protein expression were detected by real-time quantitative PCR and Western blot analysis. Results The number of H9C2 cells treated with different concentrations of Hcy for 24 hours decreased with the increase of Hcy concentration. Compared with the control group, the activity and apoptosis of the cells in the 2 mmol/L Hcy treatment group were reduced, and the number of cells in the folic acid combined with Hcy treatment group was significantly higher than that in the Hcy treatment group. Compared with the other groups, the total apoptosis rate of Hcy treatment group increased, methylation level decreased significantly, and the level of DNA methylation increased in the folic acid combined with Hcy treatment group. The level of DNMT1 mRNA significantly increased only in the folic acid treatment group, and the levels of DNMT1, DNMT3a and DNMT3b were not significantly changed. Conclusion Folic acid can relieve the damage of Hcy to myocardial cells by DNA methylation.


Assuntos
Apoptose , Metilação de DNA , Ácido Fólico/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Animais , Linhagem Celular , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , Homocisteína , Ratos
19.
Cancer Radiother ; 23(6-7): 677-681, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31494038

RESUMO

In radiation therapy, a renewed interest is emerging for the study of spatially fractionated irradiation. In this article, a few applications using spatial fractionation of the dose will be discussed with a focus on proton minibeam radiation therapy. Examples of calculated dose (1D profiles and 2D dose distributions) and biological evidence obtained so far will be presented for various spatially fractionated techniques GRID, micro- and minibeam radiation therapy. Recent results demonstrating that proton minibeam radiation therapy leads to an increase in normal tissues sparing will be discussed, which opens the door to a dose escalation in the tumour and a possibly efficient treatment of very radioresistant tumours.


Assuntos
Fracionamento da Dose de Radiação , Neoplasias/radioterapia , Órgãos em Risco/efeitos da radiação , Terapia com Prótons/métodos , Animais , Humanos , Lesões por Radiação/prevenção & controle , Tolerância a Radiação , Ratos
20.
Chem Biol Interact ; 312: 108819, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499052

RESUMO

Cannabidiol (CBD), a compound obtained from Cannabis sativa, has wide range of therapeutic properties, including mitigation of diabetes and neurodegeneration. Cerebral ischemia and consequent learning disabilities are aggravated in elderly diabetic subjects. However, there are no studies showing the effect of CBD treatment in elderly diabetes patients suffering cerebral ischemia. The present work tested the hypothesis that CBD treatment improves metabolic dysfunctions in middle-aged diabetic rats submitted to chronic cerebral hypoperfusion. In this work, 350-day-old male Wistar streptozotocin-induced diabetic rats were used. To induce cerebral ischemia was used a chronic cerebral hypoperfusion (CCH), surgically, via the four-vessel occlusion/internal carotid artery (4-VO/ICA). Four diabetic groups were established: Non-CCH Treated Diabetic (DNT), CCH Treated Diabetic (DCT), Non-CCH Vehicle Diabetic (DNV), and CCH Vehicle Diabetic (DCV). Vehicle groups were not treated with CBD. The animals were treated during 30 days with 10 mg CBD/Kg bw/day. After treatment, the animals were euthanized, and blood levels of glucose, insulin, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, fructosamine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. DCT group presented reduction of hyperglycemia and an increase of insulinemia. Also was observed lower fructosamine, LDL, HDL, triglycerides and total cholesterol levels. AST and ALT concentration were reduced in CBD treated groups. CBD may be used as therapeutic tool to protect metabolism against injuries from diabetes aggravated by cerebral ischemia.


Assuntos
Isquemia Encefálica/patologia , Canabidiol/uso terapêutico , Diabetes Mellitus Experimental/patologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/análise , Isquemia Encefálica/complicações , Colesterol/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Insulina/sangue , Masculino , Ratos , Ratos Wistar
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