RESUMO
Intestinal development plays a critical role in physiology and disease in early life and has long-term effects on the health status throughout the lifespan. Maternal high-fat diet (HFD) fuels the inflammatory reaction and metabolic syndrome, disrupts intestinal barrier function, and alters gut microbiota in offspring. The aim of this study was to evaluate whether polar lipid-enriched milk fat globule membrane (MFGM-PL) supplementation in maternal HFD could promote intestinal barrier function and modulate gut microbiota in male offspring. Obese female rats induced by HFD were supplemented with MFGM-PL during pregnancy and lactation. The offspring were fed HFD for 11 weeks after weaning. MFGM-PL supplementation to dams fed HFD decreased the body weight gain and ameliorated abnormalities of serum insulin, lipids, and inflammatory cytokines in offspring at weaning. Maternal MFGM-PL supplementation promoted the intestinal barrier by increasing the expression of Ki-67, lysozyme, mucin 2, zonula occludens-1, claudin-3, and occludin. Additionally, MFGM-PL supplementation to HFD dams improved gut dysbiosis in offspring. MFGM-PL increased the relative abundance of Akkermansiaceae, Ruminococcaceae, and Blautia. Concomitantly, maternal MFGM-PL treatment increased short-chain fatty acids of colonic contents and G-protein-coupled receptor (GPR) 41 and GPR 43 expressions in the colon of offspring. Importantly, the beneficial effects of maternal MFGM-PL intervention persisted to offspring's adulthood, as evidenced by increased relative abundance of norank_f_Muribaculaceae, Peptostreptococcaceae and Romboutsia and modulated the taxonomic diversity of gut microbiota in adult offspring. In summary, maternal MFGM-PL supplementation improved intestinal development in the offspring of dams fed with HFD, which exerted long-term beneficial effects on offspring intestinal health.
Assuntos
Dieta Hiperlipídica , Microbioma Gastrointestinal , Camundongos , Gravidez , Masculino , Ratos , Animais , Feminino , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Glicolipídeos/farmacologia , Suplementos NutricionaisRESUMO
Microplastics (MPs) contamination is widely found in marine organisms. Marine traditional Chinese medicines (MTCM) are derived from marine organisms, but there are no relevant reports on detecting MPs in MTCM. This study selected samples of MTCM from two representative pharmaceutical companies, Brand F and Brand Z, including mother-of-pearl, stone cassia, seaweed, pumice, oyster, kombu, calcined Concha Arcae, cuttlebone, and clam shell to detect and analyze the presence of MPs. The abundance, type, color, size, and composition of MPs were investigated. Varying degrees of MPs contamination was present in all MTCM. The abundance of MPs in different MTCM ranged from 0.07 to 9.53 items/g. Their type, color, and size are similar, mainly fiber, transparent and size <2 mm. The composition of MPs is primarily made of cotton, cellulose and rayon. This study contributes to the first record of MPs in MTCM. Our results show that microplastic pollution is common in MTCM, which may cause potential risk to patients consuming MTCM.
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Microplásticos , Poluentes Químicos da Água , Humanos , Plásticos , Medicina Tradicional Chinesa , Poluentes Químicos da Água/análise , Monitoramento AmbientalRESUMO
Multiple myeloma (MM) is an incurable condition and the second most common hematological malignancy. Over the past few years, there has been progress in the treatment of MM, but most patients still relapse. Multiple myeloma stem-like cells (MMSCs) are believed to be the main reason for drug resistance and eventual relapse. Currently, there are not enough therapeutic agents that have been identified for eradication of MMSCs, and thus, identification of the same may alleviate the issue of relapse in patients. In the present study, we showed that luteolin (LUT), a natural compound obtained from different plants, such as vegetables, medicinal herbs, and fruits, effectively inhibits the proliferation of MM cells and overcomes bortezomib (BTZ) resistance in them in vitro and in vivo, mainly by decreasing the proportion of ALDH1+ cells. Furthermore, RNA sequencing after LUT treatment of MM cell lines and an MM xenograft mouse model revealed that the effects of the compound are mediated through inhibition of transforming growth factor-ß signaling. Similarly, we found that LUT also significantly reduced the proportion of ALDH1+ cells in primary CD138+ plasma cells. In addition, LUT could overcome the BTZ treatment-induced increase in the proportion of ALDH1+ cells, and the combination of LUT and BTZ had a synergistic effect against myeloma cells. Collectively, our findings suggested that LUT is a promising agent that manifests MMSCs to overcome BTZ resistance, alone or in combination with BTZ, and thus, is a potential therapeutic drug for the treatment of MM.
Assuntos
Antineoplásicos , Mieloma Múltiplo , Humanos , Animais , Camundongos , Bortezomib/farmacologia , Mieloma Múltiplo/patologia , Luteolina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Apoptose , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/tratamento farmacológico , Transdução de Sinais , Fator de Crescimento Transformador beta/farmacologia , Antineoplásicos/farmacologiaRESUMO
Although ginseng leaf is a good source of health-beneficial phytochemicals, such as polyphenols and ginsenosides, few studies have focused on the variation in compounds and bioactivities during leaf thermal processing. The efficiency of far-infrared irradiation (FIR) between 160 °C and 200 °C on the deglycosylation of bioactive compounds in ginseng leaves was analyzed. FIR treatment significantly increased the total polyphenol content (TPC) and kaempferol production from panasenoside conversion. The highest content or conversion ratio was observed at 180 °C (FIR-180). Major ginsenoside contents gradually decreased as the FIR temperature increased, while minor ginsenoside contents significantly increased. FIR exhibited high efficiency to produce dehydrated minor ginsenosides, of which F4, Rg6, Rh4, Rk3, Rk1, and Rg5 increased to their highest levels at FIR-190, by 278-, 149-, 176-, 275-, 64-, and 81-fold, respectively. Moreover, significantly increased antioxidant activities were also observed in FIR-treated leaves, particularly FIR-180, mainly due to the breakage of phenolic polymers to release antioxidants. These results suggest that FIR treatment is a rapid and efficient processing method for producing various health-beneficial bioactive compounds from ginseng leaves. After 30 min of treatment without leaf burning, FIR-190 was the optimum temperature for producing minor ginsenosides, whereas FIR-180 was the optimum temperature for producing polyphenols and kaempferol. In addition, the results suggested that the antioxidant benefits of ginseng leaves are mainly due to polyphenols rather than ginsenosides.
Assuntos
Panax , Folhas de Planta , Temperatura , Antioxidantes , Ginsenosídeos , Raios Infravermelhos , Quempferóis , Panax/química , Panax/efeitos da radiação , Folhas de Planta/química , Folhas de Planta/efeitos da radiação , PolifenóisRESUMO
Chitosan oligosaccharides (COSs), oligomers of decomposed chitosan possess many biological functions including immunomodulatory, antitumor, and antiinflammation. The aim of this study was to investigate the protective effects of COS against free fatty acid (FFA)-induced cellular hepatic steatosis and underlying mechanisms in HepG2 cells. Results showed that COS significantly reduced the lipid contents and elevated the activities of antioxidant enzymes including total-superoxide dismutase, glutathione peroxidase, and catalase in FFA-stimulated HepG2 cells. COS phosphorylated the acetyl-CoA carboxylase and reduced both mRNA and protein levels of lipogenesis markers including fatty acid synthase and sterol regulatory element-binding protein 1c. COS also significantly increased the expression levels of fatty acid oxidation-related factors including carnitine palmitoyltransferase 1A, acyl-coenzyme A oxidase 1, and peroxisome proliferators-activated receptor α. Besides, COS markedly phosphorylated AMP-activated protein kinase (AMPK). The inhibition of lipogenesis and the enhancement of fatty acid oxidation induced by COS were all blocked by AMPK antagonist (compound C), showing that the attenuation of hepatic steatosis by COS was dependent on AMPK activation. In conclusion, COS attenuated hepatic steatosis via suppressing lipid synthesis and enhancing fatty acid oxidation. AMPK was also involved in the alleviation of hepatic steatosis by COS. These results indicated that COS might be used as a potential ingredient to ameliorate nonalcoholic fatty liver disease. PRACTICAL APPLICATIONS: Nonalcoholic fatty liver disease (NAFLD) has been regarded as pathological fat deposition in the liver, which includes a range of pathologies, from steatosis to steatohepatitis, fibrosis, and cellular carcinoma. Our findings demonstrated that Chitosan oligosaccharides (COS) attenuated steatosis via improving lipid metabolism. COS suppressed lipogenesis and also enhanced fatty acid oxidation. Besides, the underlying molecular mechanism whereby COS elicited these beneficial effects has also been proved to be through the modulation of upstream protein kinase, AMP-activated protein kinase. This study provides new knowledge to support that COS might be used as a food supplement for the prevention of NAFLD.
Assuntos
Quitosana , Hepatopatia Gordurosa não Alcoólica , Proteínas Quinases Ativadas por AMP/genética , Quitosana/farmacologia , Ácidos Graxos/metabolismo , Células Hep G2 , Humanos , Lipídeos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Oligossacarídeos/farmacologiaRESUMO
Milk contains about 4% fat globules with its surface covered by polar lipids. Despite the abundant consumption of dairy products, the biological effects of dietary milk polar lipids on metabolic health have only been sparsely examined. Maternal obesity results in neurodevelopmental disorders and cognitive impairment in offspring. Considering the importance of maternal nutrition, the effects of polar lipids-enriched milk fat globule membrane (MFGM-PL) supplementation to dams during pregnancy and lactation on neurodevelopment and its long-term programming effects on offspring cognition were examined. Female Sprague-Dawley rats consumed 8-week control diet (CON) or high-fat diet (HFD) to induce obesity before mating. Then, female rats were fed CON or HFD with or without the supplementation of 400 mg/kg body weight MFGM-PL during pregnancy and lactation. The offspring were fed 11-week HFD after weaning. MFGM-PL supplementation to obese dams suppressed body weight gain and hyperinsulinemia in both dams and offspring. Offspring born to obese dams displayed delayed neurological reflexes development, impaired neurogenesis before weaning, and cognitive impairment in adulthood, which were recovered by maternal MFGM-PL supplementation. Insulin resistance and aberrant brain-derived neurotrophic factor signaling were induced in the hippocampus of neonatal and adult offspring due to maternal and progeny HFD, but recovered by maternal MFGM-PL administration. This study demonstrates that maternal MFGM-PL supplementation can promote neurodevelopment and exert long-term effects against HFD-induced cognitive impairment in offspring via alleviating hippocampal insulin resistance. Hence, MFGM-PL is a promising ingredient for exerting beneficial programming effects on the brain health of offspring.
Assuntos
Sistema Nervoso Central/crescimento & desenvolvimento , Cognição/efeitos dos fármacos , Suplementos Nutricionais , Lipídeos/farmacologia , Leite/química , Obesidade , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Lipídeos/administração & dosagem , Masculino , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Ratos , Ratos Sprague-Dawley , Receptor trkB/genética , Receptor trkB/metabolismoRESUMO
BACKGROUND: During the process of shearing the ligamentum flavum, rotating the working channel, and manipulating the annulus fibrosis, the sinuvertebral nerve and the spinal nerve root can be irritated, inducing intolerable back and leg pain. Thus, general anesthesia is recommended and well accepted by most surgeons when performing percutaneous endoscopic lumbar discectomy (PELD) via the interlaminar approach. The aim of our study was to explore the efficacy and safety of percutaneous endoscopy interlaminar lumbar discectomy with gradient local anesthesia (LA) in patients with L5/S1 disc herniation. METHODS: This retrospective study was conducted between December 2017 and June 2018. The study included 50 consecutive patients who met the study criteria, had single-level L5/S1 disc herniation, and underwent PELD via the interlaminar approach under gradient LA. Different concentrations of local anesthetic compound (LAC) were injected into different tissues inside and outside the ligamentum flavum to complete gradient LA. The evaluation criteria included the intraoperative satisfaction score, visual analog scale (VAS) score, Oswestry Disability Index (ODI), complications, and adverse reactions. RESULTS: The intraoperative satisfaction score was consistently over 7, with an average score of 9.3 ± 0.7, indicating that LAC can achieve satisfactory pain control throughout the PELD operation without additional anesthesia. The postoperative VAS score and ODI were dramatically improved at each follow-up interval (P < 0.001, respectively). There was no serious complication such as dural rupture caused by puncture, dural laceration caused by manipulation under endoscopy, total spinal anesthesia, iatrogenic nerve root injury, epidural hematoma, infections, or local anesthetic-related adverse reactions. Three patients experienced transient postoperative dysesthesia of the lower limbs that gradually recovered within 24 h. CONCLUSIONS: Gradient local anesthesia can satisfactorily and safely control intraoperative pain during the PELD via the interlaminar approach. It can not only improve intraoperative satisfaction, but also reduce local anesthesia-related adverse reactions and surgery-related complications.
Assuntos
Anestesia Local/métodos , Discotomia Percutânea/métodos , Deslocamento do Disco Intervertebral/cirurgia , Complicações Intraoperatórias/prevenção & controle , Vértebras Lombares/cirurgia , Dor/prevenção & controle , Adulto , Estudos de Viabilidade , Feminino , Humanos , Ligamento Amarelo , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Retrospectivos , Segurança , Resultado do Tratamento , Adulto JovemRESUMO
SCOPE: Milk fat globule membrane (MFGM), which contains abundant polar lipids and glycoproteins, can narrow the gap in growth and development between breast-fed and infant-formula-fed babies. The objective of this study is to evaluate the effect of MFGM supplementation in infant formula on intestinal epithelium maturation, tight junctions, and gut colonization in rat pups. METHODS AND RESULTS: Sprague Dawley rat pups consume one of the five diets from postnatal day 8, including rat breastfeeding (BF), infant formula (IF), and infant formula containing MFGM at 260 mg kg-1 body weight (BW), 520 mg kg-1 BW, or 1040 mg kg-1 BW. Results show that MFGM supplementation in infant formula can facilitate intestinal mucosal barrier maturation via promoting intestinal proliferation and differentiation, and increasing tight junction proteins. In addition, compared with that of the IF pups, the intestinal flora composition of MFGM-supplemented pups is more similar to that of BF pups. CONCLUSION: MFGM supplementation in infant formula can restore the intestinal development in infant-formula-fed pups, which suggests that the supplementation of MFGM in infant formula can better mimic breast milk.
Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Glicolipídeos/farmacologia , Glicoproteínas/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Microbioma Gastrointestinal/fisiologia , Glicolipídeos/administração & dosagem , Glicolipídeos/química , Glicoproteínas/administração & dosagem , Glicoproteínas/química , Humanos , Lactente , Fórmulas Infantis , Mucosa Intestinal/fisiologia , Gotículas Lipídicas/química , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Proteínas de Junções Íntimas/metabolismoRESUMO
BACKGROUND: We investigated the efficacy and safety of thread-embedding acupuncture (TEA) for chronic low back pain (LBP) in a randomized controlled pilot trial with the aim of laying the foundation for a large-scale randomized controlled trial on this topic. METHODS: Forty participants were recruited for this two-arm, assessor-blinded randomized controlled pilot trial. The participants were randomly allocated to a TEA group (experimental group) or an acupuncture group (control group). The TEA group received TEA once every 2 weeks for 8 weeks (four sessions in total), while the acupuncture group received acupuncture twice per week for 8 weeks (16 sessions in total). The primary outcome was the visual analog scale (VAS) score for pain and the secondary outcomes were short-form McGill Pain Questionnaire (SF-MPQ) and Oswestry Disability Index (ODI) scores. Assessments were performed at screening and at 2, 4, 6, 8, and 10 weeks after treatment initiation (the 10-week assessment was conducted at 2 weeks after treatment cessation). RESULTS: Of the 40 participants, 36 completed the study and four dropped out. Both the TEA group and the acupuncture group showed significant improvements in VAS, SF-MPQ, and ODI scores in a time-dependent manner. Furthermore, with regard to ODI, a significant interaction between group and time was observed, with the two groups exhibiting a different pattern of change at 8 weeks according to contrast analysis with Bonferroni's correction. No serious adverse event occurred, and hematological and biochemical test findings were within normal limits. CONCLUSION: This pilot study has provided basic data for a larger clinical trial to demonstrate the efficacy and safety of TEA for chronic LBP. TRIAL REGISTRATION: Clinical Research Information Service of the Korea National Institute of Health, ID: KCT0001819 . Registered on 15 February 2016.
Assuntos
Terapia por Acupuntura/métodos , Dor Crônica/terapia , Dor Lombar/terapia , Adulto , Dor Crônica/diagnóstico , Dor Crônica/fisiopatologia , Feminino , Humanos , Dor Lombar/diagnóstico , Dor Lombar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Projetos Piloto , República da Coreia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: We investigated the efficacy and safety of miniscalpel acupuncture (MA) for knee osteoarthritis (KOA) in an assessor-blinded randomized controlled pilot trial; this would provide information for a large-scale randomized controlled trial. METHODS: Participants (n = 24) were recruited and randomly allocated to the MA group (experimental) or acupuncture group (control). The MA group received treatment once a week for 3 weeks (total of 3 treatments), while the acupuncture group received treatment two times per week for 3 weeks (total of 6 treatments). The primary outcome was pain as assessed by a visual analogue scale (VAS). The secondary outcomes (intensity of current pain, stiffness, and physical function) were assessed using the short-form McGill Pain Questionnaire (SF-MPQ) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Assessments were performed at baseline, 1, 2, and 3 during treatment and at week 5 (2 weeks after the end of treatment). RESULTS: Of the 24 participants, 23 completed the study. Both groups showed significant improvements in VAS, SF-MPQ, and WOMAC. However, there were no significant differences between the MA and acupuncture groups. No serious adverse event occurred and blood test results were within normal limits. CONCLUSION: Our results suggest that although both MA and acupuncture provide similar effects with regard to pain control in patients with KOA, MA may be more effective in providing pain relief because the same relief was obtained with fewer treatments. A large-scale clinical study is warranted to further clarify these findings.
RESUMO
BACKGROUND: Chronic neck pain is a common musculoskeletal disease during the lifespan of an individual. With an increase in dependence on computer technology, the prevalence of chronic neck pain is expected to rise and this can lead to socioeconomic problems. We have designed the current pilot study to evaluate the efficacy and safety of miniscalpel acupuncture treatment combined with non-steroidal anti-inflammatory drugs (NSAIDs) in patients with chronic neck pain. METHODS: This seven-week clinical trial has been designed as an assessor-blinded, randomized controlled trial with three parallel arms. Thirty-six patients will be recruited and randomly allocated to three treatment groups: miniscalpel acupuncture treatment; NSAIDs; and miniscalpel acupuncture treatment combined with NSAIDs. Patients in the miniscalpel acupuncture and combined treatment groups will receive three sessions of miniscalpel acupuncture over a three-week period. Patients in the NSAIDs and combined treatment groups will receive zaltoprofen (one oral tablet, three times a day for three weeks). Primary and secondary outcomes will be measured at weeks 0 (baseline), 1, 2, 3 (primary end point), and 7 (four weeks after treatment completion) using the visual analogue scale and the Neck Disability Index, EuroQol 5-dimension questionnaire, and Patients' Global Impression of Change scale, respectively. Adverse events will also be recorded. DISCUSSION: This pilot study will provide a basic foundation for a future large-scale trial as well as information about the feasibility of miniscalpel acupuncture treatment combined with NSAIDs for chronic neck pain. TRIAL REGISTRATION: Korean Clinical Research Information Service registry, KCT0002258 . Registered on 9 March 2017.
Assuntos
Terapia por Acupuntura/métodos , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Crônica/terapia , Cervicalgia/terapia , Terapia por Acupuntura/efeitos adversos , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Projetos PilotoRESUMO
BACKGROUND AND OBJECTIVES: Chinese herbal drug Da-Cheng-Qi decoction (DCQD) has been widely used for decades to treat acute pancreatitis (AP). Previous trials are mostly designed to state the potential mechanisms of the therapeutic effects rather than to detect its whole effect on metabolism. This study aimed to investigate the efficacy of DCQD on metabolism in AP. METHODS: Twenty-two male adult Sprague-Dawley rats were randomized into three groups. AP was induced by retrograde ductal infusion of 3.5% sodium taurocholate solution in DCQD and AP group, while 0.9% saline solution was used in sham operation (SO) group. Blood samples were obtained 12 h after drug administration and a 600 MHz superconducting Nuclear Magnetic Resonance (NMR) spectrometer was used to detected plasma metabolites. Principal Components Analysis (PCA) and Partial Least Squares-Discriminant Analysis after Orthogonal Signal Correction (OSC-PLS-DA) were applied to analyze the Longitudinal Eddy-delay (LED) and Carr-Purcell-Meiboom-Gill (CPMG) spectra. RESULTS: Differences in concentrations of metabolites among the three groups were detected by OSC-PLS-DA of 1HNMR spectra (both LED and CPMG). Compared with SO group, DCQD group had higher levels of plasma glycerol, glutamic acid, low density lipoprotein (LDL), saturated fatty acid (FA) and lower levels of alanine and glutamine, while the metabolic changes were reversed in the AP group. CONCLUSIONS: Our results demonstrated that DCQD was capable of altering the changed concentrations of metabolites in rats with AP and 1HNMR-based metabolomic approach provided a new methodological cue for systematically investigating the efficacies and mechanisms of DCQD in treating AP.
Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/uso terapêutico , Pancreatite/tratamento farmacológico , Pancreatite/metabolismo , Alanina/sangue , Animais , Biotransformação , LDL-Colesterol/sangue , Ácidos Graxos/sangue , Ácido Glutâmico/sangue , Glutamina/sangue , Glicerol/sangue , Espectroscopia de Ressonância Magnética , Masculino , Metabolômica , Ratos , Ratos Sprague-DawleyRESUMO
rAd5-hTERTC27, a replication-defective adenovirus vector carrying hTERTC27, has been proposed for possible use against hepatocellular carcinoma (HCC). In this study, we investigated the long-term toxicity of rAd5-hTERTC27 in SD rats and Cynomolgus monkeys. rAd5-hTERTC27 was administered intravenously once a week for 13 weeks followed by a one-month recovery period. As of 4 months, all animals displayed overall good health. Anti-adenoviral antibodies emerged in a dose-independent manner. The levels of complement components, C3 and C4, in the rAd5-hTERTC27 middle-dose and high-dose groups and C4 in the rAd5-EGFP group increased significantly after the 2nd treatment in monkeys. Slight-mild pathological changes of the liver occurred only in the rAd5-hTERTC27 high-dose group (2/16) in rats and not in any other group in either rats or monkeys. With the increase of the dose, the incidence of lymphocyte depletion in the spleen of rats and reactive hyperplasia of the splenic corpuscle in monkeys increased. However, the changes in the liver and spleen were reversible. Given the above data, intravenous administration of rAd5-hTERTC27 (up to 4×10(10)VP/kg in rats and 0.9×10(10)VP/kg in monkeys) appears to be well-tolerated, providing support for its potentially safe use in clinical trials for the treatment of HCC.
Assuntos
Adenoviridae , Vetores Genéticos/administração & dosagem , Vetores Genéticos/toxicidade , Telomerase/administração & dosagem , Telomerase/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Injeções Intravenosas , Neoplasias Hepáticas/tratamento farmacológico , Macaca fascicularis , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Fatal familial insomnia (FFI) is an autosomal dominant prion disease clinically characterized by rapidly progressive insomnia, prominent autonomic alterations and behavioral disturbance. The D178N mutation of the prion protein gene (PRNP) on chromosome 20 in conjunction with methionine at codon 129 is a molecular feature. Although the neuropathological characteristics of FFI are well documented, the neuropathologic and pathogenic features of FFI patients remain poorly understood. Six brain regions of postmortem brains from 3 FFI patients were examined using immunohistochemistry, western blot analyses and quantitative real-time PCR. In all 3 brain specimens, reactive astrogliosis was found to be more severe in the thalamus than in the cortex regions. Western blot analyses showed that all three brains expressed PrP, but only 2 were associated with significantly weak proteinase K (PK) resistance. However, the conformational stabilities of PrPSc in the 3 FFI brains were significantly weaker than those presented in a G114V genetic Creutzfeldt-Jakob disease (gCJD) case. Immunohistochemistry and western blot analyses showed comparable amounts of neuron-specific enolase (NSE)-positive stained cells and NSE protein among the different regions in the three brains. In addition, the transcriptional levels of glial fibrillary acidic protein (GFAP) and NSE-specific mRNAs were coincident with the expression of these proteins. In conclusion, in the present study, we described the detailed regional neuropathology of FFI cases.
Assuntos
Giro do Cíngulo/patologia , Insônia Familiar Fatal/patologia , Córtex Pré-Frontal/patologia , Tálamo/patologia , Adulto , Animais , Autopsia , Western Blotting , Cromossomos Humanos Par 20/genética , Códon/genética , Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/patologia , Endopeptidase K/genética , Endopeptidase K/metabolismo , Feminino , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Giro do Cíngulo/metabolismo , Humanos , Imuno-Histoquímica , Insônia Familiar Fatal/genética , Masculino , Metionina/genética , Metionina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mutação , Linhagem , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Córtex Pré-Frontal/metabolismo , Proteínas Priônicas , Príons/genética , Príons/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Manejo de Espécimes , Tálamo/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVE: To investigate the effect of prescription compatibility on the pharmacokinetics of components from Dachengqi Decoction (DCQD, ) in rats. METHODS: Twenty-four male rats were randomly and equally divided into the DCQD group, Dahuang (Radix et Rhizoma Rhei, Polygonaceae) group, Houpo (Magnolia officinalis Rehd., Magnoliaceae) group, and Zhishi (Fructus Aurantii Immaturus, Rutaceae) group. The blood samples were collected before dosing and subsequently at 10, 15, 20, 30, 45 min, 1, 2, 4, 8, and 12 h following gavage. The levels of aloe-emodin, rhein, emodin, chrysophanol, honokiol, magnolol, hesperidin, and naringin in rat serum were quantified using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for pharmacokinetic study. RESULTS: The area under the curve (AUC), mean retention time (MRT), the peak concentration (C(max)) of aloe-emodin, rhein, emodin, and chrysophanol in the DCQD group were significantly different compared with the Dahuang group (P <0.05, respectively). The mean plasma concentration, C(max), and the absorption of Dahuang's component in the DCQD group were obviously lower at each time point than those in the Dahuang group, while the elimination process of Dahuang's component was obviously delayed (P <0.05). Half-lives of aloe-emodin, chrysophanol, and rhein were also extended in the DCQD group (P <0.05, respectively). In the DCQD group, the mean plasma concentration, AUC, C(max) and absorption of honokiol, and magnolol were significantly lower (P <0.01, respectively) at each time point than those in the Houpo group, while the drug distribution half-life time (T(1/2α)), the drug eliminated half-life time (T(1/2ß)), MRT, and time of peak concentration (T(max)) were significantly delayed (P <0.05, respectively). Pharmacokinetic parameters of hesperidin and naringin in the Zhishi group were not significantly different as compared with the DCQD group (P >0.05, respectively), while the MRT of naringin was significantly longer. CONCLUSIONS: The compatibility in Chinese medicine could affect the drug's pharmacokinetics in DCQD, which proves that the prescription compatibility principle of Chinese medicine formulations has its own pharmacokinetic basis.
Assuntos
Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Administração Oral , Animais , Antraquinonas/administração & dosagem , Antraquinonas/sangue , Antraquinonas/farmacocinética , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/sangue , Compostos de Bifenilo/farmacocinética , Incompatibilidade de Medicamentos , Emodina/administração & dosagem , Emodina/sangue , Emodina/farmacocinética , Flavanonas/administração & dosagem , Flavanonas/sangue , Flavanonas/farmacocinética , Hesperidina/administração & dosagem , Hesperidina/sangue , Hesperidina/farmacocinética , Lignanas/administração & dosagem , Lignanas/sangue , Lignanas/farmacocinética , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/sangue , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Intra-abdominal hypertension (IAH) is a recognized prognostic marker for severity of severe acute pancreatitis (SAP) and has a strong impact on the clinical course of SAP. Previous studies indicate that a Da-Cheng-Qi Decoction (DCQD) is beneficial in the treatment of SAP. The purpose of this study was to evaluate the effect of modified DCQD on IAH in patients with SAP. METHODS: Between January 2008 and December 2008, 42 patients from the West China Hospital were randomized into either the DCQD or control group (n = 21 in each group). Mortality, intra-abdominal pressure (IAP), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, C-reactive protein (CRP), oxygenation index, Balthazar CT score, rate of renal failure, decompression rate, intensive care unit (ICU) transfer rate, and length of hospital stay (LOS) were compared between the two groups. RESULTS: Compared to the control group, the modified DCQD treatment significantly decreased IAP (P < 0.05) and APACHE II (P < 0.05) scores on days 4 - 8, CRP on day 8 (P < 0.01), renal failure rate (P < 0.05), and LOS (P < 0.05). The oxygenation index was significantly improved in the DCQD group compared with the control group (P < 0.05). No significant differences in the Balthazar CT score, shock rate, ICU transfer rate, or mortality occurred between the two groups. CONCLUSIONS: The modified DCQD can effectively relieve IAH and decrease LOS for patients with SAP. Larger clinical trials are needed to confirm these findings.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão Intra-Abdominal/tratamento farmacológico , Pancreatite/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To test the hypothesis "lung and large intestine are interior exteriorly related" through investgating into the effect of Dacheng qi tang (DCQT) on intra abdominal hypertension (IAH) and acute lung injury (ALI) in rats with acute pancreatitis. METHODS: Male SD rats were randomly divided into three groups with ten rats for each group: rats with sham-operations (SO); rats with acute necrosis pancreatitis (ANP); rats with ANP plus DCQT treatment. ANP was induced by retrograde infusion of 5% taurocholic acid into pancreatic duct. Two hours after operations, 10 mL/kg of normal saline was orally adminstered to the rats in both SO and ANP groups, whereas 10 mL/kg DCQT was adminstered to the rats in the treatment group. Aterial blood, pancreas and lung tissues were collected for biomarkers and histopathology 24 hours after operations. Intra-abdominal pressure and intestinal propulsion rate were also measured. RESULTS; DCQT treatment reduced intra-abdominal pressure and improved intestinal propulsion rate compared with those treated with saline (P < 0.05). The ANP rats treated with DCQT had lower wet to dry weight ratio, and milder myeloperoxidase activity and histopathology changes in pancreas and lung than those treated with saline (P < 0.05). Higher pressure of oxygen (PO2) was found in the rats treated with DCQT, while no difference in PCO2 was found between the DCQT and ANP groups (P > 0.05). Only two rats in the ANP group died. CONCLUSION: DCQT can effectively relieve IAH and cure ALI at the same time in rats with acute pancreatitis. The result provides evidence to support the hypothesis "lung and large intestine are interior exteriorly related".
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Hipertensão Intra-Abdominal/tratamento farmacológico , Pancreatite Necrosante Aguda/complicações , Extratos Vegetais/uso terapêutico , Lesão Pulmonar Aguda/etiologia , Animais , Hipertensão Intra-Abdominal/etiologia , Masculino , Pancreatite Necrosante Aguda/tratamento farmacológico , Fitoterapia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the changing trends of clinical management for severe acute pancreatitis (SAP) with integrative medicine. METHODS: Clinical data of 1 561 patients with SAP from 1980 to 2005 was retrospectively analyzed. The mortality and morbidity of complications were compared. RESULTS: Of the 1 561 patients, 400 patients accepted surgical operation, while the rest were treated conservatively with integrative medicine. There was a change toward conservative management together with Chinese purgative herbal medication use after 1990 (22.4% from 1980-1990 compared with 45.5% from 1991-1993) because of high postoperative mortality. From 1994-2005, the treatment integrating Western medicine with Chinese herbal medications came to be preferred over the classic Western operation-based method. This change was associated with decreased morbidity (35.4% in 1980-1990 compared with 24.7% in 1991-1993 and 11.0% in 1994-2005, P<0.05) and lower mortality (40.52% of 1980-1990 compared with 17.17% of 1991-1993 and <10.25% of 1994-2005, P<0.05). CONCLUSION: The combination of conservative management with Chinese herbal medicines is preferable to classic Western medicine treatment to reduce morbidity and mortality of SAP, while surgery becomes a supplemental option.
Assuntos
Medicina Integrativa , Pancreatite/terapia , Doença Aguda , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/mortalidadeRESUMO
OBJECTIVE: To investigate the effect of dexamethasone (Dx) combined with modified Dachengqi Decoction (DCQD), a Chinese herbal decoction for purgation, on patients with severe acute on patients with severe acute, a Chinese herbal decoction for purgation, on patients with severe acute pancreatitis (SAP) accompanied with systematic inflammatory response syndrome (SIRS). METHODS: A total of 81 patients diagnosed as SAP were randomly assigned to a control group or treatment group according to a random number table generated from an SPSS software. The patients in the control group (38 cases) received standard treatment and Chinese herbal decoction for purgation; those in the treatment group (43 cases) received additional 1 mg/(kg·d) dexamethasone (Dx) treatment for three days based on the above treatment. The mortality rate, acute respiratory distress syndrome (ARDS), renal failure, hemorrhage, sepsis, pancreatic pseudocyst, pancreatic abscess, operability, and days of hospitalization were compared between the two groups. RESULTS: Three patients in the control group and eight patients in the treatment group dropped out from the study with a drop-out rate of 7.8% and 18.6%, respectively, and no statistics difference was shown between the two groups (P>0.05). Dx treatment significantly reduced ARDS rate and shortened the length of hospitalization compared to those in the control group (7/35, 20.0% versus 15/35, 42.9%, P=0.0394; 32.5±13.2 days versus 40.2±17.5 days, P=0.0344). Other parameters including the mortality rate were not significant different between the two groups. CONCLUSION: Dx combined with DCQD could decrease the risk of developing ARDS in SAP patients with SIRS and shorten their length of hospitalization.
Assuntos
Catárticos/administração & dosagem , Dexametasona/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Pancreatite/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Catárticos/efeitos adversos , Dexametasona/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Observação , Pancreatite/complicações , Pancreatite/mortalidade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/epidemiologia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
AIM: To investigate the effect of severe acute pancreatitis (SAP) on pharmacokinetics of Da-Cheng-Qi Decoction (DCQD) components in rats. METHODS: Rats were divided into SAP group and sham-operation group as a control group (n = 6). Rhein, chrysophanol, rheochrysidin, magnolol, hesperidin and naringin in DCQD were quantified in rat serum by high performance liquid chromatography tandem mass spectrometry for studying their pharmacokinetics. RESULTS: Early absorption of each DCQD component was tended to degrade in SAP group after treatment with DCQD by gavage. The C(max) (chrysophanol, P = 0.0059; rheochrysidin, P = 0.0288; magnolol, P = 0.0487; hesperidin, P = 0.0277; naringin, P = 0.0023) and AUC (rhein, P = 0.0186; chrysophanol, P = 0.0013; magnolol, P = 0.001; hesperidin, P = 0.0081; naringin, P = 0.0272) of DCQD component were obviously lower in SAP group than in control group. The T(1/2alpha) of chrysophanol and rheochrysidin (P = 0.0467 and 0.0005, respectively) and T(max) of chrysophanol and rheochrysidin (P = 0.0101 and 0.0037, respectively) lasted longer in SAP group than in control group. CONCLUSION: SAP can significantly impact the absorption of DCQD components in rats and their pharmacokinetic parameters.