RESUMO
OBJECTIVE: To observe the effects of different doses of acetyl-L-carnitine (ALC) on hindlimb motor function and spinal cord tissue structure in rats with spinal cord injury. The study will provide theoretical and experimental evidences for acetyl-L-carnitine's clinical treatment. METHODS: Fifty-five SD rats aged 8-10 weeks were randomly divided into high, medium and low-dose drug intervention (SCI + ALC) group, injury group (SCI) and sham group for behavioral evaluation, MAD and SOD detection, as well as HPLC detection and HE staining. BBB scores and Rivlin experiments were performed to evaluate hindlimb motor function in each group. The morphology and structure of spinal cord tissue was detected by HE staining. Another 9 rats were randomly divided into Sham group, SCI group and ALC group for TUMEL detection of apoptosis. RESULTS: The BBB scores of the high, medium, and low dose SCI+ALC groups were significantly higher than those in the SCI group. The medium and high-dose ALC groups had significant differences (Pï¼0.01), and the hindlimb motor function was significantly improved in rats. The maximum tilt angle of the Rivlin experiment was observed. The SCI+ALC group had a significantly increased angle compared with the SCI group (Pï¼0.05), the medium and high-dose ALC group had a significant difference (Pï¼0.01). Compared with the SCI group, the tissue structure of ALC high-dose group was improved significantly, the number of inflammatory cells and red blood cells was decreased, and the nucleolus of the nerve cells was unclear. The SOD activity of the SCI+ALC group was significantly higher than that of the SCI group, while the MDA content was significantly decreased(Pï¼0.05), the middle and high dose ALC groups were significantly different (Pï¼0.01). HPLC chromatogram showed that the SCI+ALC fresh serum sample and the ALC standard solution had the same absorption spectrum at 260 nm, while the Sham group and SCI group serum samples did not show spectral values there, which indicated that the same substance as the standard existed in the sample of SCI+ALC group. TUNEL staining showed that the apoptosis signal was occasionally seen in the sham group, and the apoptosis signal was significantly decreased in the ALC high-dose group compared with the SCI group(Pï¼0.05). CONCLUSION: ALC can promote the recovery of hindlimb motor function in rats with spinal cord injury, inhibit oxidative stress and apoptosis, and repair the damaged spinal cord tissue.
Assuntos
Acetilcarnitina , Traumatismos da Medula Espinal , Medula Espinal , Acetilcarnitina/farmacologia , Acetilcarnitina/uso terapêutico , Animais , Membro Posterior/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Medula Espinal/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet-induced obesity, but in Sv129 mice accentuates obesity. RESULTS: Using HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF feeding rather than obesity development led to distinct changes in the gut microbiota. We observed a robust increase in alpha diversity, gene count, abundance of genera known to be butyrate producers, and abundance of genes involved in butyrate production in Sv129 mice compared to BL6 mice fed either a LF or a HF diet. Conversely, the abundance of genes involved in propionate metabolism, associated with increased energy harvest, was higher in BL6 mice than Sv129 mice. CONCLUSIONS: The changes in the composition of the gut microbiota were predominantly driven by high-fat feeding rather than reflecting the obese state of the mice. Differences in the abundance of butyrate and propionate producing bacteria in the gut may at least in part contribute to the observed differences in obesity propensity in Sv129 and BL6 mice.
Assuntos
Butiratos/metabolismo , Dieta Hiperlipídica , Gorduras na Dieta/metabolismo , Microbioma Gastrointestinal , Propionatos/metabolismo , Animais , Bacteroidetes/crescimento & desenvolvimento , Bacteroidetes/isolamento & purificação , Inibidores de Ciclo-Oxigenase/farmacologia , Firmicutes/crescimento & desenvolvimento , Firmicutes/isolamento & purificação , Genoma Bacteriano/genética , Indometacina/farmacologia , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade , Prostaglandina-Endoperóxido Sintases/metabolismoRESUMO
Injection of alkali, surfactant and polymer (ASP) into oil reservoir can substantially increase oil recovery compared with water-flooding strategy. However, the effects of these agents on the microbial diversity and community structure, which is important for water management and corrosion control in oil industry, are hitherto poorly understood. Here, we disclosed the microbial diversity and community structure in the produced water collected from four producing wells of an ASP-flooded oilfield at Daqing, China, using high-throughput sequencing technique. Results showed that the average pH in produced water was as high as 9.65. The microbial diversity varied from well to well, and the Shannon diversity index was between 2.00 to 3.56. The Proteobacteria (85.5%-98.3%), γ-proteobacteria (83.7%-97.8%), and alkaliphilic Nitrincola (51.8%-82.5%) were the most dominant phylogenetic taxa at the phylum, class, and genus levels, respectively. A total of 12 potentially sulfide-producing genera were detected, and the most abundant taxon was Sulfurospirillum (0.4%-7.4%). The microbial community of ASP-flooded petroleum reservoir was distinct, showing an alkaliphilic or alkalitolerant potential; a reduced diversity and more simple structure were observed compared with those of the water-flooded petroleum reservoirs that were previously reported.
Assuntos
Petróleo , Microbiologia da Água , Álcalis , Bactérias , China , Filogenia , Polímeros , RNA Ribossômico 16S , Tensoativos , ÁguaRESUMO
Fish oil rich in n-3 polyunsaturated fatty acids is known to attenuate diet-induced obesity and adipose tissue inflammation in rodents. Here we aimed to investigate whether different carbohydrate sources modulated the antiobesity effects of fish oil. By feeding C57BL/6J mice isocaloric high-fat diets enriched with fish oil for 6 wk, we show that increasing amounts of sucrose in the diets dose-dependently increased energy efficiency and white adipose tissue (WAT) mass. Mice receiving fructose had about 50% less WAT mass than mice fed a high fish oil diet supplemented with either glucose or sucrose, indicating that the glucose moiety of sucrose was responsible for the obesity-promoting effect of sucrose. To investigate whether the obesogenic effect of sucrose and glucose was related to stimulation of insulin secretion, we combined fish oil with high and low glycemic index (GI) starches. Mice receiving the fish oil diet containing the low-GI starch had significantly less WAT than mice fed high-GI starch. Moreover, inhibition of insulin secretion by administration of nifedipine significantly reduced WAT mass in mice fed a high-fish oil diet in combination with sucrose. Our data show that the macronutrient composition of the diet modulates the effects of fish oil. Fish oil combined with sucrose, glucose, or high-GI starch promotes obesity, and the reported anti-inflammatory actions of fish oil are abrogated. In conclusion, our data indicate that glycemic control of insulin secretion modulates metabolic effects of fish oil by demonstrating that high-GI carbohydrates attenuate the antiobesity effects of fish oil.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Carboidratos da Dieta/metabolismo , Óleos de Peixe/uso terapêutico , Índice Glicêmico/fisiologia , Insulina/sangue , Obesidade/metabolismo , Animais , Fármacos Antiobesidade/metabolismo , Relação Dose-Resposta a Droga , Óleos de Peixe/metabolismo , Glucose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/induzido quimicamente , Obesidade/prevenção & controle , SacaroseRESUMO
BACKGROUND: Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance. METHODOLOGY/PRINCIPAL FINDINGS: We fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the proteinâ¶sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state. CONCLUSIONS/SIGNIFICANCE: The background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Óleos de Peixe/uso terapêutico , Obesidade/tratamento farmacológico , Sacarose/efeitos adversos , Tecido Adiposo/metabolismo , Animais , Calorimetria Indireta , Dieta Hiperlipídica/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/induzido quimicamente , Reação em Cadeia da PolimeraseRESUMO
This paper is to study the inhibitory effect of water soluble polymers--methyl cellulose (MC), hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC-M), poloxamer (F68) and polyvidon (PVP) on osthole (OST) crystallization and investigate the impact of polymer concentration and viscosity on crystallization behavior. Also, UV spectrophotometry method was used to determine the drug concentration at different time point to draw the OST concentration-time curve. Results show that HPMC has the most significant inhibition effect on OST crystallization, and drug concentration level is 1.61 times higher than that in control solution within 8 h followed by PVP (1.54) and MC (1.45) respectively. The kinetics of OST recrystallization can be described using first-order reaction, and the crystallization rate constants obtained by analyzing the regression equation indicate that HPMC-60SH-4000 and HPMC-60SH-10000 can greatly influence OST crystal formation. The dissolution rate of drugs precipitated from water-soluble polymer solutions is faster compared with controls in pH 1.2 HCl and pH 6.8 phosphate buffers, which demonstrated that water-soluble polymers can not only change the behavior of drug crystallization but markedly improve the dissolution rate of water insoluble drugs.
Assuntos
Celulose , Química , Cnidium , Química , Cumarínicos , Química , Cristalização , Derivados da Hipromelose , Cinética , Metilcelulose , Química , Plantas Medicinais , Química , Poloxâmero , Química , Polímeros , Química , Povidona , Química , Solubilidade , ViscosidadeRESUMO
Conjugation of bile acids (BAs) to the amino acids taurine or glycine increases their solubility and promotes liver BA secretion. Supplementing diets with taurine or glycine modulates BA metabolism and enhances fecal BA excretion in rats. However, it is still unclear whether dietary proteins varying in taurine and glycine contents alter BA metabolism, and thereby modulate the recently discovered systemic effects of BAs. Here we show that rats fed a diet containing saithe fish protein hydrolysate (saithe FPH), rich in taurine and glycine, for 26 days had markedly elevated fasting plasma BA levels relative to rats fed soy protein or casein. Concomitantly, the saithe FPH fed rats had reduced liver lipids and fasting plasma TAG levels. Furthermore, visceral adipose tissue mass was reduced and expression of genes involved in fatty acid oxidation and energy expenditure was induced in perirenal/retroperitoneal adipose tissues of rats fed saithe FPH. Our results provide the first evidence that dietary protein sources with different amino acid compositions can modulate the level of plasma bile acids and our data suggest potential novel mechanisms by which dietary protein sources can affect energy metabolism.
Assuntos
Ácidos e Sais Biliares/sangue , Gordura Intra-Abdominal/metabolismo , Hidrolisados de Proteína/administração & dosagem , Animais , Proteínas Alimentares/administração & dosagem , Metabolismo Energético/efeitos dos fármacos , Peixes , Glicina/administração & dosagem , Lipídeos/análise , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taurina/administração & dosagem , Triglicerídeos/sangueRESUMO
<p><b>OBJECTIVE</b>To investigate the efficacy of different interventional therapies for primary hepatic cell cancer (HCC).</p><p><b>METHODS</b>1126 HCC patients before or after hepatectomy were treated by different kinds of interventional therapies: transcatheter arterial chemoembolization (TACE), TACE and radio-frequency ablation (RFA), Chinese traditional medicine and biotherapy after TACE or the transcatheter arterial infusion (TAI). The results of liver function, alpha-fetoprotein, imaging, color-ultrasonography and survival rate were reviewed.</p><p><b>RESULTS</b>874 patients were followed up for 2 to 63 months. The overall 1-, 3-, 5-year survival rate was 67.8% , 28.7% and 18.8%, respectively. The 1-, 3-, 5-year survival rate of patients who received TACE before hepatectomy was 74.7%, 41.4% and 36.9% ; after hepatectomy 78.9%, 40.4% and 37.5%, respectively. The response rate ( PR + NC) of TACE and RFA was 93.4%, and the 1-, 3-year survival rate was 74.5% and 36.8%, respectively, after TACE and RFA. The response rate (PR + NC) of TACE was 83.2% with 1-, 3-, 5-year survival rate of 69.3%, 21.7%, 8.4% after TACE, respectively. The response rate (PR + NC) of TAI was 27.5% with 1-, 2-year survival rate of 11. 6% and 0 after TAI. The Child grade of liver function, color-ultrasonography and alpha-fetoprotein of TACE + RFA group, TACE and TAI were compared. There was no significant difference between each above mentioned index among TACE, RFA or TACE groups.</p><p><b>CONCLUSION</b>Compared with other modalities, transcatheter arterial chemoembolization (TACE) before or after hepatectomy is more effective than other interventional therapies for primary hepatocellular cancer, whereas, if combined with radiofrequency ablation (TAI), it is much more effective than TACE alone.</p>
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Hepatocelular , Cirurgia Geral , Terapêutica , Ablação por Cateter , Quimioembolização Terapêutica , Métodos , Terapia Combinada , Seguimentos , Hepatectomia , Infusões Intra-Arteriais , Neoplasias Hepáticas , Cirurgia Geral , Terapêutica , Análise de Sobrevida , Resultado do Tratamento , alfa-Fetoproteínas , MetabolismoRESUMO
Serotonin is a specific in vitro substrate for human UDP-glucuronosyltransferase (UGT) 1A6. In this study, the contribution of UGT1A6 to the glucuronidation of endogenous structural analogs of serotonin, including 5-hydroxytryptophol, N-acetylserotonin, and 6-hydroxymelatonin, was evaluated using available recombinant human UGT isoforms, human liver microsomes, and liver microsomes from animals that do not express functional UGT1A6 (Gunn rats and cats). Only UGT1A6 and UGT1A9 were found to glucuronidate 5-hydroxytryptophol at a concentration of 2 mM, although the glucuronidation rate with UGT1A6 was over 10 times that of UGT1A9. K(m) values for human liver microsomes (156, 141, and 134 microM) were most similar to that of expressed UGT1A6 (135 microM) but vastly different from that of UGT1A9 (3674 microM). 5-Hydroxytryptophol glucuronidation by human liver microsomes (n = 54) correlated well with serotonin glucuronidation (R(s) = 0.83) and UGT1A6 protein content (R(s) = 0.85). 5-Hydroxytryptophol also competitively inhibited serotonin glucuronidation by human liver microsomes (K(i) = 291 microM) and UGT1A6 (K(i) = 200 microM). N-acetylserotonin was glucuronidated most extensively by UGT1A6, although UGT1A9 and UGT1A10 showed moderate catalysis. 6-Hydroxymelatonin was glucuronidated largely by UGT1A9 and UGT1A10 but not at all by UGT1A6. Gunn rat liver glucuronidation rates for serotonin, 5-hydroxytryptophol, N-acetylserotonin, and 6-hydroxymelatonin were 11, 5, 32, and 3%, respectively, of that of normal rat liver. Cat liver microsomes did not glucuronidate serotonin, whereas relatively low activities were observed for the other indole substrates. In conclusion, these results indicate that human UGT1A6 plays a predominant role in the glucuronidation of 5-hydroxytryptophol and N-acetylserotonin, whereas 6-hydroxymelatonin is not a substrate for this enzyme.
Assuntos
Glucuronosiltransferase/metabolismo , Hidroxitriptofol/metabolismo , Serotonina/análogos & derivados , Serotonina/metabolismo , Adolescente , Adulto , Idoso , Animais , Gatos , Criança , Pré-Escolar , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Humanos , Hidroxitriptofol/química , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Gunn , Ratos Wistar , Especificidade por Substrato/fisiologiaRESUMO
OBJECTIVE: To identify and determine the concentrations of phytoestrogens in commercial dog foods. SAMPLE POPULATION: 24 commercial dog foods, including 12 moist or dry extruded commercial dog foods that contained soybeans or soybean fractions and 12 foods without any soybean-related ingredients listed on the label. PROCEDURE: Foods were analyzed for phytoestrogen content, including 4 isoflavones (genistein, glycitein, daidzein, and biochanin A), 1 coumestan (coumestrol), and 2 lignans (secoisolariciresinol and matairesinol) by use of acid-methanol hydrolysis and high-pressure liquid chromatography with UV-absorbance detection. Phytoestrogens were identified and quantified by reference to authentic standards. RESULTS: Isoflavones, coumestans, and lignans were undetectable in diets that did not list soybean-related ingredients on the label. Only 1 of the 12 diets that included soybean or soybean fractions had undetectable concentrations of phytoestrogens and that product contained soy fiber. The major phytoestrogens were the isoflavones daidzein (24 to 615 microg/g of dry matter) and genistein (4 to 238 microg/g of dry matter). CONCLUSIONS AND CLINICAL RELEVANCE: Soybean and soybean fractions are commonly used ingredients in commercial dog foods. Dietary intake of phytoestrogens may have both beneficial and deleterious health effects. Our results indicated that certain commercial dog foods contain phytoestrogens in amounts that could have biological effects when ingested long-term.
Assuntos
Ração Animal/análise , Isoflavonas/análise , Isoflavonas/química , Preparações de Plantas/análise , Preparações de Plantas/química , Proteínas de Soja/análise , Animais , Cromatografia Líquida de Alta Pressão , Cães , Hidrólise , Fitoestrógenos , Espectrofotometria UltravioletaRESUMO
AIM:To establish the HPLC fingerprint of methanol-resoluble component of processing Gentiana scraba Bge collected from different habits to provide evidence for quality control and quality evaluation of Gentiana scraba Bge.METHODS:Ten batches of processing Gentiana scraba Bge were measured by RP-HPLC,and the mutual mode was made by the similarity degree evaluating system 2004 of Chromatographic Fingerprint of Traditional Chinese Medicine promulgated by Chromatographic condition,consisted of Agilent-Eclipse-XDB-C_ 18-column and gradient elution with methanol-water,the detection wavelength was at 254 nm,flow rate was at 1.0 mL/min and the column temperature was at 20 ℃.RESULTS:The mutual mode of processing Gentiana scraba Bge was set up and the similarity of fingerprints of processing Gentiana scraba Bge from different habits was gained.CONCLUSION:According to the analysis of statistics,this method is steady,accurate with good repeatability and can be used as standardization implantation and quality control of Gentiana scraba Bge.