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To reduce the problems of poor solubility, high in vivo dosage requirement, and weak targeting ability of paclitaxel (PTX), a hyaluronic acid-octadecylamine (HA-ODA)-modified nano-structured lipid carrier (HA-NLC) was constructed. HA-ODA conjugates were synthesized by an amide reaction between HA and ODA. The hydrophobic chain of HA-ODA can be embedded in the lipid core of the NLC to obtain HA-NLC. The HA-NLC displayed strong internalization in cluster determinant 44 (CD44) highly expressed MCF-7 cells, and endocytosis mediated by the CD44 receptor was involved. The HA-NLC had an encapsulation efficiency of PTX of 72.0%. The cytotoxicity of the PTX-loaded nanoparticle HA-NLC/PTX in MCF-7 cells was much stronger than that of the commercial preparation Taxol®. In vivo, the HA-NLC exhibited strong tumor targeting ability. The distribution of the NLCs to the liver and spleen was reduced after HA modification, while more nanoparticles were aggregated to the tumor site. Our results suggest that HA-NLC has excellent properties as a nano drug carrier and potential for in vivo targeting.
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To reduce the problems of poor solubility, high in vivo dosage requirement, and weak targeting ability of paclitaxel (PTX), a hyaluronic acid-octadecylamine (HA-ODA)-modified nano-structured lipid carrier (HA-NLC) was constructed. HA-ODA conjugates were synthesized by an amide reaction between HA and ODA. The hydrophobic chain of HA-ODA can be embedded in the lipid core of the NLC to obtain HA-NLC. The HA-NLC displayed strong internalization in cluster determinant 44 (CD44) highly expressed MCF-7 cells, and endocytosis mediated by the CD44 receptor was involved. The HA-NLC had an encapsulation efficiency of PTX of 72.0%. The cytotoxicity of the PTX-loaded nanoparticle HA-NLC/PTX in MCF-7 cells was much stronger than that of the commercial preparation Taxol®. In vivo, the HA-NLC exhibited strong tumor targeting ability. The distribution of the NLCs to the liver and spleen was reduced after HA modification, while more nanoparticles were aggregated to the tumor site. Our results suggest that HA-NLC has excellent properties as a nano drug carrier and potential for in vivo targeting.
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OBJECTIVE: To prepare, the conjugated linoleic acid-paclitaxel conjugate self-assembled nanoparticles (CLA-PTX NPs) by nanoprecipitation. METHODS: The Dynamic light scattering, nuclear magnetic resonance spectroscopy, raman spectroscopy, fourier transform infrared spectroscopy and nitrogen element distribution of CLA-PTX NPs were studied. RESULTS: The hydroxyl groups (C-4 and C-10 of PTX) and the acetyl groups (C-1 and C-7 of PTX) were on the surface of CLA-PTX NPs, CLA carbon chain, the benzene ring (C-2 and C-3' of PTX) and the amide bond (C-3' of PTX) were inside the CLA-PTX NPs. CONCLUSION: It is speculated that the self-assembly of CLA-PTX is that the non-polar CLA carbon chain spontaneously aggregates inward due to hydrophobic interaction, and the hydrophilic oxygen-containing groups of PTX (hydroxyl group and carbonyl group) are on the surface of the nanoparticle to form nanoparticles.
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Objective To establish a reversed phase high performance liquid chromatography method which couldb be ap-plied to determine the content of paclitaxel stearate(PTX-SA)and its bioactive metabolites paclitaxel(PTX)simultaneously. Methods Diazepam was chosen to be the internal standard and liquid-liquid extraction method was used for the preparation of sample solution with methyl tert-butyl ether.The two compounds were separated on Agilent Eclipse plus C18column (4.6 mm×250 mm,5 μm)with gradient elution by using mobile phase of acetonitrile(A)-methanol(B)-water(C),the detection wavelength was 227 nm and the column temperature was 30 ℃.The flow rate was 1 ml/min and the injection volume was 20 μl.Results The standard curve exhibited good linearity within the concentration of PTX-SA from 0.5-250 μg/ml(r=0.997 6)and PTX from 0.05-25 μg/ml(r=0.997 9),meanwhile the LOQ of PTX-SA and PTX were 0.15 and 0.05 μg/ml, respectively.The recoveries were both larger than 90% with RSD less than 5%.Moreover,the RSD of intra-day and inter-day assays were both less than 5%.Conclusion The method was simple,effective,stable and accurate which could be suitable for the determination of PTX-SA and PTX in pharmacokinetic study.
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OBJECTIVE:To explore the therapeutic effect of early use of alprostadil and the effects on PTX-3,renal function and stability of carotid plaque in patients with acute cerebral infarction. METHODS:93 patients with acute cerebral infarction in our hospital from Aug. 2011 to Aug. 2015 were selected,and divided into observation group(47 cases,2 case withdrew from the test and 45 cases completed the test)and control group(46 cases,1 case withdrew from the test and 45 cases completed the test) by odd and even number of registration order. Control group was given Citicoline sodium injection 0.5 g + Extract of ginkgo biloba leaves injection 20 ml added into Sodium chloride injection(NS)250 ml,ivgtt,qd;observation group was additionally given Al-prostadil injection 20 μg added to NS 250 ml,ivgtt,qd. They were treated for 2 weeks. Clinical efficacy,and the differences of PTX-3,blood urea nitrogen(BUN),serum creatinine(SCr),24 h urinary protein(Upro),stability of carotid plaque before and after treatment,and the incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate in observation group(91.1%)was higher than control group(73.3%),the difference was statistically significant(P0.05). After treatment,PTX-3,BUN, SCr,24 h Upro in 2 groups decreased,and observation group was lower than control group;stability of carotid plaque in observa-tion group(100.0%)was higher than control group(64.0%),the differences were no statistically significant(P0.05). CONCLU-SIONS:The early use of alprostadil is effective for acate cerebral in farction,and can obviously reduce PTX-3 and improve renal functions,increase stability of carotid plaque with good safety.
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Pentraxin (PTX) 3 is a typical long PTX. As an inflammatory marker, the plasma PTX3 level is elevated in atherosclerosis, cardiovascular disease, infection, inflammation, autoimmune disease and tissue injury. Recently studies have shown that the plasma PTX3 level rapidly increased during the acute phase of ischemic cerebrovascular disease. Detection of plasma PTX3 level may be contribute to the diagnosis, treatment and prognostic judgment of acute cerebral infarction.
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Sepsis is the life-threatening response to infection which can lead to tissue damage, organ failure, and death. In the current study, the effect of orally administered D-glucose on the mortality and the blood glucose level induced by D-Galactosamine (GaLN)/lipopolysaccharide (LPS)-induced sepsis was examined in ICR mice. After various amounts of D-glucose (from 1 to 8 g/kg) were orally fed, sepsis was induced by injecting intraperitoneally (i.p.) the mixture of GaLN /LPS. Oral pre-treatment with D-glucose dose-dependently increased the blood glucose level and caused a reduction of sepsis-induced mortality. The oral post-treatment with D-glucose (8 g/kg) up to 3 h caused an elevation of the blood glucose level and protected the mortality observed in sepsis model. However, D-glucose post-treated at 6, 9, or 12 h after sepsis induction did not affect the mortality and the blood glucose level induced by sepsis. Furthermore, the intrathecal (i.t.) pretreatment once with pertussis toxin (PTX; 0.1 microg/5 ml) for 6 days caused a reduction of D-glucose-induced protection of mortality and hyperglycemia. Furthermore, once the hypoglycemic state is continued up to 6 h after sepsis initiated, sepsis-induced mortality could not be reversed by D-glucose fed orally. Based on these findings, it is assumed that the hypoglycemic duration between 3 and 6 h after the sepsis induction may be a critical time of period for the survival. D-glucose-induced protective effect against sepsis-induced mortality appears to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Finally, the production of hyperglycemic state may be critical for the survival against the sepsis-induced mortality.
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Animals , Mice , Blood Glucose , Glucose , GTP-Binding Proteins , Hyperglycemia , Mice, Inbred ICR , Mortality , Pertussis Toxin , Sepsis , Spinal CordABSTRACT
Objective To determine the maximum tolerated dose ( MTD) and dose?limiting toxicity ( DLT) of weekly PTX and DDP concurrent postoperative radiotherapy in Chinese women with high?and intermediate?risk early cervical cancer. Methods Women with high risks postoperative cervical carcinoma, ECOG≤2 were eligible. Pelvis RT (6/10 MV X?ray,3DCRT 40 Gy/20f,para?metrial boost 10?20 Gy/5?10f) was followed by 2?4f brachytherapy applications ( 192 Ir,5 Gy/f) . Concurrent weekly chemotherapy was started at DDP 20 mg/m2 and PTX 10 mg/m2 weekly,and escalated in three?patient cohorts according to 3+3 methods. Results 25 patients were enrolled and treated over seven doses levels until dose?limiting toxicity (DLT) was reached. Median age was 48 years (range,34?66).All of patients finished RT in 7 weeks. Grade 3,4 non?hematologic toxicities were diarrhea and observed in two patients (4 cycles,DLT) at level 7.Grade 3,4 hematologic,principally leukopenia and neutropenia,and occurs late cycles. One grade 4 leukopenia and neutropenia was observed at dose level 6 but not seen in three additional patients. No one was delayed treatment time by concurrent chemotherapy.22 patients finished 6 cycles. Median follow?up is 59. 5 months. Three patients have died of cancer metastasis and recurrence. One patient has died of respiratory failure. Conclusions Combination PTX and DDP administered concurrently with pelvic EBRT can be safely administered at the MTD of DDP 35 mg/m2 and PTX 30 mg/m2 weekly for six cycles in Chinese women with postoperative cervical cancer.
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Objective To evaluate the effect of suberoylanilide hydroxamic acid(SAHA) or/and paclitaxel(PTX) on lethality and autophagy of human ovarian cancer OC3 cells,and to explore whether the combination of the two drugs has a synergistic function.Methods The morphology of OC3 cells was treated with SAHA and/or PTX, and then the morphology of treated OC3 cells was observed under an inverted microscope, cell proliferation was detected by MTT assay and autoph-agy was analyzed by AO/EB double staining assay.The synergistic effect of SAHA and/or PTX was analyzed by factorial design and gold formula method.Results After treatment with SAHA and/or PTX, the morphology of OC3 cells in the combination group ( SAHA+PTX) displayed significant morphological changes.OC3 cells became less adherent and refrac-tive than in other groups.Cell proliferation by MTT assay demonstrated that the growth inhibition rate of the combination groups was higher than in groups treated with SAHA or PTX respectively( P<0.05) .Furthermore, the synergistic effect af-ter treatment with a combination of SAHA with PTX was proved by the factorial design and gold formula method.The auto-phagy rate of the combined groups was significantly higher than in single treatment groups (P<0.05) by AO/EB double staining.Conclusion SAHA and PTX can inhibit the survival of OC3 cells and induce its autophagy.The two drugs have synergistic antitumor effects.
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BACKGROUND AND OBJECTIVES: The aim of this study was to examine the hypothesis that pentraxin 3 (PTX3) can have a diagnostic value for predicting anatomical complexity of coronary artery stenosis as measured by the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score. SUBJECTS AND METHODS: We investigated the association of systemic arterial PTX3 with SYNTAX score among 500 patients with ischemic heart disease assigned to medical treatment (251), percutaneous coronary intervention (PCI) (197), or coronary artery bypass graft (CABG) (52). RESULTS: The clinical judgment of the cardiologists was near-perfectly concordant with the SYNTAX score. Mean {99% confidence intervals (CIs)} SYNTAX scores were 5.8 (5.1-6.6), 18.4 (17.1-19.8), and 33.2 (32.8-33.6) in patients assigned to medical therapy, PCI, and CABG, respectively. The AROC (95% CIs) for discriminating between patients with and without a high SYNTAX score (>23) was 0.920 (0.895-0.946) for systemic arterial levels of PTX3. As the systemic arterial level of PTX3 increased, the SYNTAX scores also increased almost in a curvilinear fashion, with the value corresponding to the SYNTAX score of 23 being 0.29 ng . dL-1. This cutpoint achieved a sensitivity of 0.66 (0.57-0.74), a specificity of 0.94 (0.91-0.96), a positive predictive value of 0.79 (0.70-0.87), and a negative predictive value of 0.89 (0.85-0.92). CONCLUSION: We observed that systemic arterial levels of PTX3 were associated with the SYNTAX score in a curvilinear fashion. The discriminatory power of systemic arterial levels of PTX3 for a high SYNTAX score was excellent. The interesting finding of this study was the near perfect concordance between the decisions made by the cardiologists based on their clinical judgment and the SYNTAX score. The systemic arterial PTX3 level of 0.29 ng . dL-1 was highly specific for diagnosing complex coronary artery stenosis.
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Humans , Angiography , Coronary Artery Bypass , Coronary Artery Disease , Coronary Stenosis , Judgment , Myocardial Ischemia , Percutaneous Coronary Intervention , Sensitivity and Specificity , Taxus , Thoracic Surgery , TransplantsABSTRACT
BACKGROUND: Conventional biomarkers cannot always establish the cause of pleural effusions; thus, alternative tests permitting rapid and accurate diagnosis are required. The primary aim of this study is to assess the ability of pentraxin-3 (PTX3) in order to diagnose the cause of pleural effusion and compare its efficacy to that of other previously identified biomarkers. METHODS: We studied 118 patients with pleural effusion, classified as transudates and exudates including malignant, tuberculous, and parapneumonic effusions (MPE, TPE, and PPE). The levels of PTX3, C-reactive protein (CRP), procalcitonin (PCT) and lactate in the pleural fluid were assessed. RESULTS: The levels of pleural fluid PTX3 were significantly higher in patients with PPE than in those with MPE or TPE. PTX3 yielded the most favorable discriminating ability to predict PPE from MPE or TPE by providing the following: area under the curve, 0.74 (95% confidence interval, 0.63-0.84), sensitivity, 62.07%; and specificity, 81.08% with a cut-off point of 25.00 ng/mL. CONCLUSION: Our data suggests that PTX3 may allow improved differentiation of PPE from MPE or TPE compared to the previously identified biomarkers CRP and PCT.
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Humans , Biomarkers , C-Reactive Protein , Diagnosis , Diagnosis, Differential , Exudates and Transudates , Lactic Acid , Pleural EffusionABSTRACT
Objective To observe the clinical effects of Shenqifuzheng injections combined with PTX and DDP on advanced non small cell lung cancers. Methods Fifty cases of advanced non small cell lung cancers were randomly divided into pure chemotherapy and chemotherapy combined with traditional Chinese medicine groups. The former was treated with 30 mg/m2 DDP from day 1 to day 3, 135 mg/m2 PTX only at the first day. The latter was treated with 250 ml Shenqifuzheng injections every day until the twentieth-first one, three days before the beginning of chemotherapy. After two periods of treatments, the therapeutic effects were evaluated, respectively. Results The recent effective ratios of chemotherapy combined with traditional Chinese medicine and pure chemotherapy groups were 48 % and 40 %, respectively. The former could ameliorate the physical status, the numbers of peripheral leucocytes, the decreases of blood platelet, the gastrointestinal reactions of subjects. Conclusion The Shenqifuzheng injections could increase the recent treatment effect of PTX combined with DDP on advanced non small cell lung cancers, effectively meliorate the clinical symptoms and alleviate the side effects of chemotherapy leading to improve the life qualities of subjects.
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This study was conducted to develop an animal model of uveitis resembled anterior uveitis in humans after immunization with iris-ciliary body antigen. Male Lewis rats were immunized with the buffer-and detergent insoluble bovine iris-ciliary body mixed with Complete Freund`s adjuvant (CFA) and Pertussis toxin(PTX). A soluble fraction derived from bovine melanin associated antigen(BMAA) after digestion with the proteolytic enzyme V8 protease was prepared and this soluble fraction of BMAA also induced an experimental autoimmune uveitis (EAU). On gel eletrophoresis for soluble fraction of BMAA, prominent bands between 29 kDa and 43 kDa were clealy observed. In this model, clinical anterior uveitis was induced around 2 weeks, peaked at 18 days and disappeared later than 4 weeks after immunization. Histopathological results of EAU disclosed an infiltration of inflammatory cells, mainly lymphocytes and macrophages, into iris and ciliary body as well as in part the choroid, not retina. In conclusion, we developed a model of EAU with Lewis rats after immunization with BMAA subcutaneously and confirmed the immune mediated inflammation was focused mainly on iris and ciliary body and in part on choroid as well as found that MAA might be soluble after V8 protease treatment.
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Animals , Humans , Male , Rats , Choroid , Ciliary Body , Detergents , Digestion , Immunization , Inflammation , Iris , Lymphocytes , Macrophages , Melanins , Models, Animal , Retina , Uveitis , Uveitis, Anterior , Whooping CoughABSTRACT
Objective To study the role of early release of tumor necrosis factor-?(TNF-?) and nuclear factor-?B(NF?B) activation on inflammatery mediators expression and neutrophil accumulation in the liver after ischemia/reperfusion . Methods The models of partial hepatic ischemia in Wistar rats were established. Rats received either Pentoxifylline (PTX) 50mg/kg(PTX group) or sterile saline (control group) via peritoneal injection at 1h before ischemia;Sham operation group was also established. Results Compared with control group,in PTX treatment group, the release of the TNF-?, the content of NF?B p65, expression of MIP-2 mRNAand ICAM-1 mRNA were significant decreased;the levels of MPO,AST,ALT, LDH,and W/D were also reduced significantly(all P
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Objective The paclitaxel loaded solid lipid nanoparticles (PTX-SLNs) were prepared by an ultrasonic-dispersion emulsification technique. The stability of PTX-SLNs was investigated in this study. Methods The technology was preferenced by stability, Zeta potential, particle diameter, and entrapment efficiency as indexes. The doses of lipid materials and coemulsifier, the ultrasonic time, and the ultrasonic power were investigated in detail. Results The optimum prescriptions were definited by one-factor and orthogonal test. The adjuvant: glyceryl monostearate (100/150 mg), Fabaceous Lecithin (100 mg), coemulsifier Pluronic F68∶Tween 80 (2∶1). The samples were sonicated with an energy output of 300 W in 20 min after emulsified at (75?5) ℃. Conclusion The PTX-SLNs are successfully prepared and PTX-SLNs with high stability are fairly dispersed in colloidal solution. This technology has a nice prospect with safety and reliability.