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BACKGROUND: This article aimed to discuss the efficacy and safety of endoscopic dacryocystorhinostomy (EDCR) versus external dacryocystorhinostomy (EX-DCR) for the treatment of dacryocystitis by meta-analysis. METHODS: All randomized controlled trials that met the inclusion and exclusion criteria were collected by searching the following databases: PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang, from the establishment of the database to June 2023. Meta-analysis was performed using Stata 17.0 software and review manager 5.4 software. In the collected trials, the observation group was treated with EDCR, whereas the control group was treated with EX-DCR. RESULTS: A total of 10 studies involving 969 patients were included in this analysis. There was a similar surgical success rate in the treatment of dacryocystitis between the 2 groups (RRâ =â 1.021, 95% CI [0. 803, 1.297], Pâ =â 0. 865). However, compared with the control group, patients in the observation group had a higher total effective rate of treatment (RRâ =â 1. 195, 95% CI [1. 063, 1.343], Pâ =â .003), and shorter operative time (WMDâ =â -23.640, 95% CI [-35.533, -11.747], Pâ <â .001), and less intraoperative blood loss (WMDâ =â -50.797, 95% CI [-80.339, -21.255], Pâ =â .001), shorter length of hospital stays (WMDâ =â -4.570, 95% CI [-5.992, -3.148], Pâ <â .001), and lower incidence of adverse events (RRâ =â 0.295, 95% CI [0.173, 0.504], Pâ <â .001). CONCLUSION: EDCR is an effective and safe surgical procedure for the treatment of dacryocystitis and can be used as an alternative to EX-DCR.
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Dacriocistite , Dacriocistorinostomia , Endoscopia , Humanos , Dacriocistite/cirurgia , Dacriocistorinostomia/métodos , Endoscopia/métodos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The aim of this study was to investigate the effects of different types of exercise on intestinal mechanical barrier and related regulatory factors in mice with type 2 diabetes mellitus (T2DM). The model was established by high-fat diet feeding and intraperitoneal injection of streptozocin (STZ). The mice were divided into control group, model group (free exercise), resistance exercise group (tail load-bearing ladder climbing, 5 times a week), aerobic exercise group (non-load-bearing platform running, 5 times a week at a speed of 10-15 m/min), and combined exercise group (aerobic exercise was performed on the first, third and fifth days of each week, and resistance exercise on the second and fourth days of each week). After 8 weeks of intervention, the serum lipid levels and inflammatory cytokines were measured by corresponding kits. The pathological changes of ileum were detected by HE and PAS staining. The mRNA and protein expression levels of tight junction-related proteins were detected by real-time qPCR and Western blot, respectively. Moreover, the protein expression levels of hypoxia inducible factor-1α (HIF-1α) and myosin light chain kinase (MLCK) were detected by Western blot. The results showed that all three types of exercise decreased blood glucose and body weight compared to the model group. Aerobic exercise and combined exercise decreased serum lipid (triglycerides and total cholesterol) levels, up-regulated the expression levels of ileal tight junction-related proteins and HIF-1α, improved the intestinal alkaline phosphatase (AKP) activity, reduced serum lipopolysaccharide (LPS), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and diamine oxidase (DAO) levels, and down-regulated MLCK protein expression level. These results suggest that all three types of exercise can reduce blood glucose and body weight of T2DM mice, and aerobic exercise and combined exercise can restore the damaged intestinal mechanical barrier by a mechanism involving HIF-1α-MLCK pathway.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Glicemia , Peso Corporal , Lipopolissacarídeos , CamundongosRESUMO
OBJECTIVE: To observe the effect of Lingnan fire needling combined with artificial tears in the treatment of xerophthalmia. METHODS: A total of 86 xerophthalmia patients were equally and randomly divided into treatment group and control group. The patients of both groups were received treatment with 0.1% sodium hyaluronate eye drops in their eyes 3 times a day, one drop in each eye. In addition, the patients of treatment group also treated by Lingnan fire needling on bilateral Shaoze (SI1), Neichengqi and beside lacrimal puncta once a week. The treatment was conducted for 4 consecutive weeks. Before and after 4 weeks of treatment, the clinical efficacy, visual acuity, intraocular pressure, ocular symptom score, OSDI score, fluorescence staining ï¼FLï¼ score, schemer I, tear menisci height, tear film break-up time (BUT) and eye redness index were recorded and evaluated. RESULTS: After the treatment, self-comparison showed that the symptom score, OSDI score, FL score and eye redness index were significantly decreased (P<0.05), and BUT was notably increased in both groups (P<0.05) in comparison with their own pre-treatment. The tear menisci height in the treatment group was higher than that before the treatment (P<0.05). Comparison between the two groups showed that the symptom score, OSDI score and eye redness index were obviously lower in the treatment group than in the control group (P<0.05), whereas the BUT and tear menisci height were evidently higher (P<0.05). The total effective rate of the treatment group was 84.88% (73/86), better than 76.74% (66/86) of the control group (P<0.05). CONCLUSION: Lingnan fire needling combined with 0.1% sodium hyaluronate eye drops is more effective than simple sodium hyaluronate eye drops for xerophthalmia patients, with significant curative effect and no adverse reactions.
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Agulhamento Seco , Ácido Hialurônico/uso terapêutico , Soluções Oftálmicas/uso terapêutico , Xeroftalmia , Humanos , Lágrimas , Xeroftalmia/tratamento farmacológicoRESUMO
AIMS: Hyperglycemia and insulin resistance drive intestinal barrier dysfunction in type 2 diabetes (T2DM). Vaccarin, the main active component in the semen of traditional Chinese medicine Vaccaria has a definite effect on T2DM mice. The purpose of this study was to investigate whether vaccarin can enhance the intestinal barrier function in T2DM. MAIN METHODS: The T2DM mice model was established by streptozocin and high-fat diet. Vaccarin at a dose of 1 mg/kg/day was administered. We evaluated the effects of vaccarin on gut microbiota and intestinal barrier function by 16S rRNA sequencing, Western blot, quantitative fluorescent PCR (qPCR), and morphological observation. Moreover, we constructed a single layer of the human intestinal epithelium model to determine the effect of vaccarin in vitro. RESULTS: The experimental results showed that vaccarin alleviated inflammatory mediators in serum and intestinal tissue of mice (P < 0.05), which may depend on the improvement of tight junctions and gut microbiota (P < 0.05). Activation of extracellular regulated protein kinases (Erk1/2) stimulated myosin light chain kinase (MLCK). By inhibiting ERK expression (P < 0.05), vaccarin had similar effects to ERK inhibitors. In addition, the regulation of tight junction barriers also involved the abovementioned pathways in vivo. CONCLUSION: Vaccarin could protect the intestinal barrier by inhibiting the ERK/MLCK signaling pathway and modulate the composition of the microbiota. These results suggested that vaccarin may be an effective candidate for improving intestinal barrier changes in T2DM.
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Diabetes Mellitus Tipo 2 , Animais , Diabetes Mellitus Experimental , Camundongos , RNA Ribossômico 16SRESUMO
BACKGROUND: Globally, although the jellyfish population has increased in recent years, ocular jellyfish stings remain an uncommon ophthalmic emergency, and have been rarely reported. According to a few previous reports, ocular jellyfish stings may cause anterior segment disorders, and most of these injuries were self-limited and spontaneously resolved within 24 to 48 h. CASE SUMMARY: A brother and sister both presented with severe fundus complications several years after ocular jellyfish stings and both had prolonged blurred vision. To our knowledge, such fundus lesions induced by jellyfish stings have not been reported previously. CONCLUSION: The fundus status of patients following ocular jellyfish stings should be carefully monitored in cases of irreversible ocular damage.
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In order to evaluate the present situation and the potential ecological risk of heavy metal pollution in the surface waters of eastern Chinese coastal cities, the city of Ningbo was used as an example. From surface waters in Ningbo, 255 water samples were collected. The concentrations of six heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn) were measured for the samples. The potential ecological risk of these heavy metals was evaluated by calculating health risk and cancer risk indices. The results indicate that, in the surface waters of Ningbo, the average concentrations of the six heavy metals were in the increasing order of Zn > Pb > Cr > Ni > Cd > Cu. Three of the heavy metal concentrations exceeded the national environmental quality standards for surface water (GB 3838-2002, grade â ¤), and the order of exceeding the standard:Cd > Pb > Cr. Electroplating wastewater, metal waste produced, traffic pollutant, dyes, and coatings waste were the main pollutant sources. There were some potential health risks in over 70 percent of the surface waters in Ningbo, and the surface waters of the Zhenhai and Haishu districts had the highest potential health risk. There were three major potential health risk heavy metals, and their order of increasing risk was Cd > Cr > Pb. For adults and juveniles, the average carcinogenic risk indices were 17600 and 24800 times the critical values, respectively. Moreover, over 95 percent of the risks were attributed to Cr. The potential carcinogenic risk index of commercial areas with dense population was nearly 2 times that of the city average. The results indicated that the state of heavy metal pollution in the surface waters of Ningbo was very serious, thus the government should pay more attention to this issue.
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Metais Pesados/análise , Poluentes Químicos da Água/análise , China , Cidades , Monitoramento Ambiental , Humanos , Medição de RiscoRESUMO
Berberrubine (BRB) is the primary metabolite of berberine (BBR) that has shown a stronger glucose-lowering effect than BBR in vivo. On the other hand, BRB is quickly and extensively metabolized into berberrubine-9-O-ß-D-glucuronide (BRBG) in rats after oral administration. In this study we compared the pharmacokinetic properties of BRB and BRBG in rats, and explored the mechanisms underlying their glucose-lowering activities. C57BL/6 mice with HFD-induced hyperglycemia were administered BRB (50 mg·kg-1·d-1, ig) for 6 weeks, which caused greater reduction in the plasma glucose levels than those caused by BBR (120 mg·kg-1·d-1) or BRB (25 mg·kg-1·d-1). In addition, BRB dose-dependently decreased the activity of α-glucosidase in gut of the mice. After oral administration of BRB in rats, the exposures of BRBG in plasma at 3 different dosages (10, 40, 80 mg/kg) and in urine at different time intervals (0-4, 4-10, 10-24 h) were dramatically greater than those of BRB. In order to determine the effectiveness of BRBG in reducing glucose levels, we prepared BRBG from the urine pool of rats, and identified and confirmed it through LC-MS-IT-TOF and NMR spectra. In human normal liver cell line L-O2 in vitro, treatment with BRB or BRBG (5, 20, 50 µmol/L) increased glucose consumption, enhanced glycogenesis, stimulated the uptake of the glucose analog 2-NBDG, and modulated the mRNA levels of glucose-6-phosphatase and hexokinase. However, both BBR and BRB improved 2-NBDG uptake in insulin-resistant L-O2 cells, while BRBG has no effect. In conclusion, BRB exerts a stronger glucose-lowering effect than BBR in HFD-induced hyperglycemia mice. Although BRB significantly stimulated the insulin sensitivity and glycolysis in vitro, BRBG may have a greater contribution to the glucose-lowering effect because it has much greater system exposure than BRB after oral administration of BRB. The results suggest that BRBG is a potential agent for reducing glucose levels.
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Berberina/análogos & derivados , Glucuronídeos/uso terapêutico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Animais , Berberina/administração & dosagem , Berberina/sangue , Berberina/metabolismo , Berberina/farmacocinética , Berberina/uso terapêutico , Berberina/urina , Glucuronídeos/sangue , Glucuronídeos/urina , Humanos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacocinética , Masculino , Camundongos Endogâmicos C57BL , Ratos Sprague-DawleyRESUMO
From industrial and commercial areas of Ningbo City, China, 85 surface water samples were collected. The concentrations of six heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn) in the samples were measured, and the characteristics of the spatial distributions of those metals were analyzed. Through a combination of regional characteristics and Pearson correlation coefficients of the different heavy metals, the main pollution sources of the two areas were analyzed. The potential ecological risks of these heavy metals were evaluated by considering health risk and cancer risk indices. The results indicate that the heavy metal pollution of surface waters was serious in both the industrial and commercial areas. Furthermore, the differences between the two areas were also observed. In the industrial area, the average concentrations of the six heavy metals were, from highest to lowest, in the order: Zn >>Ni>Pb> Cr> Cu> Cd, and the main sources were industrial emissions. Four heavy metal concentrations exceeded the national environmental standard, which, from highest to lowest, were in the order: Cd> Pb> Cr >>Zn. In the commercial area, the average concentrations, from highest to lowest, were in the order: Cr> Pb >>Zn> Ni> Cd> Cu, and the main sources were road pollutants. Three heavy metal concentrations exceeded the national standard, and the order, from highest to lowest, was Cd> Pb>>Cr, with Cd and Pb having the most potential health risk. In both the industrial and commercial areas, there were some potential health risks and high carcinogenic risks. Cd, Cr, and Pb have the highest potential health risks, whereas Cr is the major potentially carcinogenic metal. The commercial area had 1.7 times the potential carcinogenic risk as that of the industrial area. The government should pay more attention to heavy metal pollution of surface waters in Ningbo City, China.
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As a computer-assisted approach, molecular docking has been universally applied in drug research and development and plays an important role in the investigation and evaluation of herbal medicines. Herein, the method was used to estimate the pharmacodynamics of Mai-Luo-Ning injection, a traditional Chinese compound herbal prescription. Through investigating the interactions between several important proteins in cardiovascular system and characteristic components of the formula, its effect on cardiovascular protection was evaluated. Results showed the differences in the interactions between each component and the selected target proteins and revealed the possible mechanisms for synergistic effects of various characteristic components on cardiovascular protection. The study provided scientific evidence supporting the mechanistic study of the interactions among multi-components and targets, offering a general approach to investigating the pharmacodynamics of complicated materials in compound herbal prescriptions.
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Fármacos Cardiovasculares/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Sistema Cardiovascular/metabolismo , Sinergismo Farmacológico , Enzimas/metabolismo , Humanos , Simulação de Acoplamento MolecularRESUMO
BACKGROUND: This prospective study investigated the safety and efficacy of a therapeutic method of treating pterygium complicated with conjunctivochalasis, using pterygium excision and conjunctival autotransplantation combined with sclera fixation, followed by therapeutic contact lens application. METHODS: Fifty-seven patients (83 eyes) diagnosed as pterygium complicated with conjunctivochalasis, at our hospital from July 2011 to June 2012, were selected. Patients were treated with pterygium excision and conjunctival autotransplantation combined with sclera fixation surgery, then therapeutic bandage contact lenses were applied. The efficacy of simultaneous surgery was evaluated based on vision changes, tear dynamics, and other complications. Histopathological changes were investigated on removed bulbar conjunctival tissue, using hematoxylin eosin (HE) and Masson's trichrome staining. RESULTS: (1) Three months after the operation, the success of simultaneous surgery in the treatment of pterygium was 97.6 %, and the recurrence was 2.4 %. Based on subjective evaluation, the success of the simultaneous treatment of conjunctivochalasis was 95.2 %, and failure was 4.8 %. Based on objective evaluation, the success rate was 94.0 % and the recurrence rate was 6.0 %. (2) Visual acuity of the 83 eyes was significantly improved after surgery, and was statistically significant (X 2 = 10.29, P < 0.05). (3) Three months after surgery, the height and integrity of the tear meniscus, tear film break-up time, and chloramphenicol test results of the 83 eyes were significantly improved and there was a statistically significant difference (X 2 the height and integrity of tear meniscus = 147.24, X 2 tear film break-up time = 81.17, X 2 chloramphenicol test = 17.41, P < 0.01). (4) Complications after the operation such as granulation hyperplasia, constrictive fornix, oculomotor defect, and other complications were not observed. (5) Pathological observations, using HE and Masson's trichrome staining of removed bulbar conjunctival tissue, showed several pathological changes, including obvious squamous epithelial hyperplasia, parakeratosis, basal cell pigmentation, lamina propria hemorrhage, infiltration of lymphocytes, and reduction of elastic fibers and collagen fibers. CONCLUSION: Pterygium excision and conjunctival autotransplantation, combined with sclera fixation followed by therapeutic contact lens use was safe, effective, and suitable for simultaneous treatment of pterygium complicated with conjunctivochalasis.
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Túnica Conjuntiva/transplante , Doenças da Túnica Conjuntiva/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Pterígio/cirurgia , Esclera/cirurgia , Idoso , Doenças da Túnica Conjuntiva/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Pterígio/etiologia , Recidiva , Transplante Autólogo , Acuidade Visual/fisiologiaRESUMO
The aim of the study is to evaluate the effects of the single and mixed decoction of Thallus laminariae (kelp) and Glycyrrhiza glabra (licorice) on the metabolism and their difference. The mixed decoction of kelp and licorice and the single decoction were made and intragastrically administered to the SD rats. The effect on system metabolism, the toxicity of liver and kidney were assessed by GC-MS profiling of the endogenous molecules in serum, routine biochemical assays and histographic inspection of tissues from SD rats, separately. The mixed decoction of kelp and licorice induced more obvious pathological abnormalities in SD rats than a single decoction of kelp, while the extracts of licorice did not show any pathological change. Neither the mixed, nor the single decoction showed abnormal histopathology. After intragastric administration of extracts for 5 days, the mixed decoction induced a decrease of ALT (no significant change in the groups of single decoction) and an increase of BUN (so did the single decoction of kelp). Metabolomic profile of the molecules in serum revealed that the metabolic patterns were all obviously affected for the three groups, i.e., the mixed and single decoction of kelp and licorice. The rats given with the single decoction of kelp showed a similar pattern to that of the mixed decoction, indicating that the kelp primarily contributed the perturbation of metabolism for the mixed decoction. All three groups induced a decrease of branched chain amino acids, TCA cycle intermediates and glycolysis intermediates (e.g., pyruvic acid and lactic acid) and an increase of 3-hydroxybutyric acid. Kelp decoction showed stronger potential in reducing TCA cycle intermediates and glycolysis intermediates than the other two groups, while the levels of branched chain amino acids were the lowest after licorice extracts were given. These results suggested that the effect of the mixed decoction on metabolism was closely associated with both kelp and licorice. The continuous administration of single decoction of kelp and the mixed decoction of licorice and kelp resulted in pathological abnormalities in kidney of SD rats. The mixed decoction of kelp and licorice distinctly perturbed sera molecules and hence system metabolism, which showed associated with those of kelp and licorice. Although the metabolic effect was associated with both kelp and licorice, the results suggested kelp contributed to it primarily.
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Glycyrrhiza/química , Kelp/química , Metabolômica , Preparações de Plantas/farmacologia , Animais , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
AIM: The pentose phosphate pathway (PPP) is involved in the activity of glucose-6-phosphate dehydrogenase (G6PD) and generation of NADPH, which plays a key role in drug metabolism. The aim of this study was to investigate the effects of modulation of the PPP on drug metabolism capacity in vitro. METHODS: A pair of hepatic cell lines, ie, the cancerous HepG2 cells and normal L02 cells, was used. The expression of CYP450 enzymes, p53 and G6PD in the cells were analyzed. The metabolism of testosterone (TEST, 10 µmol/L) and dextromethorphan (DEM, 1 µmol/L), the two typical substrates for CYP3A4 and CYP2D6, in the cells was examined in the presence of different agents. RESULTS: Both the expression and metabolic activities of CYP3A4 and CYP2D6 were considerably higher in HepG2 cells than in L02 cells. The metabolism of TEST and DEM in HepG2 cells was dose-dependently inhibited by the specific CYP3A4 inhibitor ketoconazole and CYP2D6 inhibitor quinidine. Addition of the p53 inhibitor cyclic PFT-α (5, 25 µmol/L) in HepG2 cells dose-dependently enhanced the metabolism of DEM and TEST, whereas addition of the p53 activator NSC 66811 (3, 10, 25 µmol/L) dose-dependently inhibited the metabolism. Furthermore, addition of the G6PD inhibitor 6-aminonicotinamide (5, 15 µmol/L) in HepG2 cells dose-dependently inhibited the metabolism of DEM and TEST, whereas addition of the PPP activity stimulator menadione (1, 5, 15 µmol/L) dose-dependently enhanced the metabolism. CONCLUSION: Modulation of p53 and the PPP alters the metabolism of DEM and TEST, suggesting that the metabolic flux pattern of PPP may be closely involved in drug metabolism and the individual variance.
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Dextrometorfano/metabolismo , Desintoxicação Metabólica Fase I/fisiologia , Via de Pentose Fosfato/fisiologia , Testosterona/metabolismo , Linhagem Celular Tumoral , Citocromo P-450 CYP3A/metabolismo , Células Hep G2 , Humanos , Fígado/enzimologia , Fígado/metabolismoRESUMO
Morroniside is a water-soluble compound extracted from the fruit of Cornus officinalis and is used to protect lung activity against aging. In the present study, the manner in which morroniside regulates normal lung and cancer cells was examined. The human embryonic lung fibroblast (HELF) cell line and lung cancer A549 cell line, and their responses to morroniside treatment, were examined. Results showed that morroniside reverses the apoptotic effect of H2O2 on HELF cell growth, protecting cell proliferation and normal cell morphology and inhibiting apoptosis. However, these effects were not present in A549 cells. Western blotting showed that morroniside also markedly downregulated retinoblastoma protein in HELF cells. These results suggest that morroniside treatment exhibits different effects on apoptosis in HELF and A549 cells, making it a viable compound for decreasing the side effects of anticancer medicines in normal cells.
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OBJECTIVE: To observe the influence of the the transforming growth factor ß1 (TGF-ß1) eye drops on rabbit aqueous humor TGF-ß1 concentration, and to analyze the best drug concentration. METHODS: A total of 30 New Zealand white rabbits were randomly divided into 5 groups with 6 in each. Rabits in control group had PBS eye drops, group A, B, C, D adopted TGF-ß1 eye drops at 0.5, 1.0, 2.0, 4.0 mg/L, respectively, 4 times a day. Aqueous humor of right eye was extracted 1 week after administration to detect concentration changes of TGF-ß1 by ELISA; rabbits in fpur hroups adopted 2.0 mg/L eye drops to left eyes 4 times a day, 0.2 mL aqueous humor was extracted left eye at the scheduled time point 0, 30 min, 2 h, 4 h, 24 h for testing, the slit lamp was used to observe the cornea, chamber and lens. RESULTS: No obvious pathological changes in conjunctiva, cornea, rabbit conjunctival, anterior chamber, and the lens was found. Concentration of TGF-ß1 in rabbit aqueous humor in C, D group was significantly higher than the control group (P<0.05). CONCLUSIONS: TGF-ß1 eye drops at 2.0 mg/L, 4.0 mg/L can significantly increase concentration of TGF-ß1 in rabbit aqueous humor, withe good ocular surfac permeability.
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Humor Aquoso/química , Fator de Crescimento Transformador beta1/análise , Animais , Humor Aquoso/metabolismo , Córnea/química , Córnea/metabolismo , Técnicas de Diagnóstico Oftalmológico , Soluções Oftálmicas/administração & dosagem , Coelhos , Distribuição Aleatória , Fator de Crescimento Transformador beta1/administração & dosagem , Fator de Crescimento Transformador beta1/farmacocinéticaRESUMO
AIM: 20(S)-Ginsenoside Rh2 (Rh2) has shown potent inhibition on P-glycoprotein (P-gp), while most HIV protease inhibitors are both substrates and inhibitors of P-gp and CYP3A4. The aim of this study was to investigate the potential pharmacokinetic interactions between Rh2 and the HIV protease inhibitor ritonavir. METHODS: The effects of Rh2 on the cellular accumulation and transepithelial transport of ritonavir were studied in Caco-2 and MDCK-MDR1 cells. Male rats were administered Rh2 (25 or 60 mg/kg, po) or Rh2 (5 mg/kg, iv), followed by ritonavir (25 mg/kg, po). The P-gp inhibitors verapamil (20 mg/kg, po) or GF120918 (5 mg/kg, po) were used as positive controls. The concentrations of ritonavir in plasma, bile, urine, feces and tissue homogenates were analyzed using LC-MS. RESULTS: Rh2 (10 µmol/L) significantly increased the accumulation and inhibited the efflux of ritonavir in Caco-2 and MDCK-MDR1 cells, as verapamil did. But Rh2 did not significantly alter ritonavir accumulation or transport in MDCK-WT cells. Intravenous Rh2 significantly increased the plasma exposure of ritonavir while reducing its excretion in the bile, and oral verapamil or GF120918 also increased plasma exposure of ritonavir but without changing its excretion in the bile. Interestingly, oral Rh2 at both doses did not significantly change the plasma profile of ritonavir. Moreover, oral Rh2 (25 mg/kg) significantly elevated the ritonavir concentration in the hepatic portal vein, and markedly increased its urinary excretion and tissue distribution, which might counteract the elevated absorption of ritonavir. CONCLUSION: Rh2 inhibits the efflux of ritonavir through P-gp in vitro. The effects of Rh2 on ritonavir exposure in vivo depend on the administration route of Rh2: intravenous, but not oral, administration of Rh2 significantly increased the plasma exposure of ritonavir.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Ginsenosídeos/farmacocinética , Inibidores da Protease de HIV/farmacocinética , Ritonavir/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Acridinas/farmacologia , Administração Oral , Animais , Células CACO-2 , Cromatografia Líquida , Cães , Relação Dose-Resposta a Droga , Interações Medicamentosas , Ginsenosídeos/administração & dosagem , Ginsenosídeos/farmacologia , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/farmacologia , Humanos , Injeções Intravenosas , Células Madin Darby de Rim Canino , Masculino , Espectrometria de Massas , Ratos , Ratos Wistar , Ritonavir/administração & dosagem , Ritonavir/farmacologia , Tetra-Hidroisoquinolinas/farmacologia , Distribuição Tecidual , Verapamil/farmacologiaRESUMO
Metabonomics, a newly developing subject secondary to genomics, transcriptomics, and proteomics, is an important constituent part of systems biology. It is believed to be the final direction of the systems biology. It can be directly applied to understand the physiological and biochemical states by its "metabolome profile" as a whole. Therefore, it can provide a huge amount of information different from those originating from other "omics". In the modernization of Chinese materia medica research, the application of metabonomics methods and technologies has a broad potential for future development. Especially it is of important theoretical significance and application value in holistic efficacies evaluation, active ingredients studies, and safety research of Chinese materia medica.
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Medicamentos de Ervas Chinesas , Metabolômica , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Materia Medica/efeitos adversos , Materia Medica/farmacologia , ProteômicaRESUMO
Osteochondral allografting has been proved to be a useful method to treat diseased or damaged areas of joint surfaces. Operational long-term stocks of grafts which supply a buffer between procurement and utilization would contribute to the commercialization or industrialization of this technology. Vitrification has been thought to be a promising method for successful preservation of articular cartilage (AC), but high concentration cryoprotectants (CPAs) are used which may cause high cellular toxicity. An effective way to reduce CPA toxicity is to increase CPA concentration gradually while the temperature is lowered. Understanding the mechanism of CPA permeation at subzero temperatures is important for designing the cryopreservation protocol. In this research, the permeation of dimethyl sulfoxide (Me(2)SO) in ovine AC at subzero temperatures was studied experimentally. Pretreated AC discs were exposed in Me(2)SO solutions for different time (0, 5, 15, 30, 50, 80, and 120 min) at three temperature levels (-10, -20, and -30 °C). The Me(2)SO concentration within the tissue was determined by ultraviolet (UV) spectrophotometry. The diffusion coefficients were estimated to be 0.85×10(-6), 0.48×10(-6), and 0.27×10(-6) cm(2)/s at -10, -20, and -30 °C, respectively, and the corresponding activation energy was 29.23 kJ/mol. Numerical simulation was performed to compare two Me(2)SO addition protocols, and the results demonstrated that the total loading duration could be effectively reduced with the knowledge of permeation kinetics.
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Cartilagem Articular , Criopreservação/métodos , Dimetil Sulfóxido , Preservação de Tecido/métodos , Animais , Crioprotetores , Difusão , Técnicas In Vitro , Modelos Biológicos , Permeabilidade , Ovinos , VitrificaçãoRESUMO
AIM: To determine the mode of action of 5-hydroxymethylfurfural (5-HMF) extracted from wine-processed Fructus corni on hepatoprotective activities, the effects of 5-HMF on H(2)O(2)-induced human L02 hepatocytes injury was examined. MTHODS: Hepatocytes L02 injured by H(2)O(2) was treated by 5-HMF. The morphological changes of the cells were observed under inverted phase-contrast, fluorescence, and transmission electron microscopy and the activities of caspase-9 and caspase-3 were tested by enzyme-linked immunosorbent detector. RESULTS: It revealed that 5-HMF improved the morphology of H(2)O(2)-treated human L02 hepatocytes, and also inhibited the level of caspase-9 and caspase-3 of them. CONCLUSIONS: These results suggested a morphological hepatocyte protective effect and the anti-apoptosis mechanism by 5-HMF.