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This study aimed to compare the effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide content and quality characteristics of fried potato chips. The hydrolyzed pectin with molecular weight (Mw) of 8.81 ± 0.49 kDa was obtained through partial degradation of pectin (Mw: 747.57 ± 6.73 kDa) using pectinase. Results showed that both pectin and hydrolyzed pectin coating significantly inhibited acrylamide formation and inhibition rates exceeded 90 %. Hydrolyzed pectin had stronger inhibitory activity against acrylamide formation than pectin, especially when the concentration of hydrolyzed pectin was >2 %, its inhibitory rate exceeded 95 %. Compared to pectin coating, hydrolyzed pectin coating endow fried potato chips with smaller browning, higher crispness, less moisture but higher oil content. Overall, hydrolyzed pectin had better application prospects than pectin in inhibiting acrylamide formation of fried potato chips.
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Acrilamida , Pectinas , Solanum tuberosum , Solanum tuberosum/química , Pectinas/química , Acrilamida/química , Hidrólisis , Culinaria , Peso MolecularRESUMEN
Tumor penetration and the accumulation of nanomedicines are crucial challenges in solid tumor therapy. By taking advantage of the MSC tumor-tropic property, we developed a mesenchymal stem cell (MSC)-based drug delivery system in which paclitaxel (PTX)-encapsulating hyaluronic acid-poly (D,L-lactide-co-glycolide) polymeric micelles (PTX/HA-PLGA micelles) were loaded for glioma therapy. The results indicated that CD44 overexpressed on the surface of both MSCs and tumor cells not only improved PTX/HA-PLGA micelle loading in MSCs, but also promoted the drug transfer between MSCs and adjacent cancer cells. It was hypothesized that CD44-mediated transcytosis played a crucial role and allowed deep glioma penetration depending on sequential intra-intercellular delivery via endocytosis-exocytosis. MSC-micelles were able to infiltrate from normal brain parenchyma towards contralateral tumors and led to the eradication of glioma. The survival of orthotopic glioma-bearing rats was significantly extended. In conclusion, the MSC-based delivery of HA-PLGA micelles is a potential strategy for tumor-targeting drug delivery.
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Glioma , Células Madre Mesenquimatosas , Animales , Línea Celular Tumoral , Dioxanos , Portadores de Fármacos/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Glioma/tratamiento farmacológico , Ácido Hialurónico/uso terapéutico , Micelas , Paclitaxel , Polímeros/uso terapéutico , RatasRESUMEN
Objectives: Studies at the genomewide level of Parkinson's disease (PD) suggested a significant association between the Hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta isomerase 7 (HSD3B7) gene rs9938550 variant and a decreased risk for PD. But its effect has only been discussed in Caucasian populations, and no phenotypic characteristics were included. To investigate the novel variant for PD in Chinese Han populations, we performed an association analysis of rs9938550 variant in a large cohort. Methods: Using a case-control methodology, a total of 2,239 subjects (1,072 sporadic patients with PD and 1,167 control) were genotyped and the genetic association was analyzed. Results: No significant association was found between allele A of rs9938550 and PD in the entire cohort (p = .079). However, the frequency of allele A was lower in late-onset PD (LOPD) as compared with controls older than 50 years (OR = 0.62, 95% CI: 0.45-0.85, padjust = .002). Relatively lower Unified Parkinson's Disease Rating Scale scores were demonstrated in mid- to late-stage PD with GA + AA genotypes than GG genotype (padjust = .018), while other clinical features were similar between carriers and noncarriers. Conclusions: Our results support that the HSD3B7 rs9938550 variant, which is likely linked to bile acid biosynthesis, reduces the risk of LOPD in Chinese patients and might induce a benign clinical performance.
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Etnicidad/genética , Predisposición Genética a la Enfermedad/genética , Proteínas de la Membrana/genética , Enfermedad de Parkinson/genética , Anciano , Alelos , Estudios de Casos y Controles , China/etnología , Femenino , Variación Genética/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
A previous study by our group found that inhibition of nischarin promotes neurite outgrowth and neuronal regeneration in Neuro-2a cells and primary cortical neurons. In recent years, more and more studies have shown that nanomaterials have good prospects in treatment of spinal cord injury. We proposed that small interfering RNA targeting nischarin (Nis-siRNA) delivered by polyethyleneimine-alginate (PEI-ALG) nanoparticles promoted motor function recovery in rats with spinal cord injury. Direct microinjection of 5 µL PEI-ALG/Nis-siRNA into the spinal cord lesion area of spinal cord injury rats was performed. From day 7 after surgery, Basso, Beattie and Bresnahan score was significantly higher in rats from the PEI-ALG/Nis-siRNA group compared with the spinal cord injury group and PEI-ALG/Control-siRNA group. On day 21 after injection, hematoxylin-eosin staining showed that the necrotic area was reduced in the PEI-ALG/Nis-siRNA group. Immunohistochemistry and western blot assay results confirmed successful inhibition of nischarin expression and increased protein expression of growth-associated protein-43 in the PEI-ALG/Nis-siRNA group. These findings suggest that a complex of PEI-ALG nanoparticles and Nis-siRNA effectively suppresses nischarin expression, induces expression of growth-associated protein-43, and accelerates motor function recovery after spinal cord injury.
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Sequence variants in fibroblast growth factor 20 (FGF20) have been reported to be associated with Parkinson's disease (PD). We genotyped the rs591323 variant in a total of 2220 Han Chinese subjects, including 1051 patients with sporadic PD and 1169 controls, to investigate the association between rs591323 and the risk of PD. In addition, we also conducted a stratified analysis according to age at onset of PD and compared the clinical characteristics of AA + AG subjects with GG subjects. In this study, we confirmed that the A allele of rs591323 in FGF20 reduces the risk of developing sporadic PD (P = 0.013). Additionally, subjects with the AA + AG genotype have a reduced risk compared to individuals with the GG genotype (P = 0.024). This association was significant among females (P = 0.036), but was not significant among males (P = 0.266). Furthermore, no significant association was observed among either the early-onset PD group (P = 0.051) or the late-onset PD group (P = 0.187). Moreover, we demonstrated that the AA + AG subjects could not be distinguished from the GG subjects based on their clinical features. Our study is the first to demonstrate that FGF20 (rs591323) is associated with a lower risk of PD in a Southern Han Chinese population from mainland China.
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Factores de Crecimiento de Fibroblastos/genética , Predisposición Genética a la Enfermedad/genética , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Pueblo Asiatico/genética , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/etnología , Adulto JovenRESUMEN
Recent several meta-analyses and certain case-control studies suggested that the Ras-like without CAAX 2 (RIT2) rs12456492 increased the risk of Parkinson's disease (PD) in Asian and Caucasian populations. However, as so far, the association between RIT2 rs12456492 and PD is still controversial. We investigated genetic association of RIT2 rs12456492 with PD susceptibility in a Han Chinese population of 1747 ethnic Han Chinese subjects comprising 884 PD patients and 863 healthy controls. The minor allele frequency (MAF) of G at the RIT2 rs12456492 was not significantly different between the cases and the controls. Furthermore, no significant differences were observed in genotype distribution between PD patients and healthy controls for the RIT2 rs12456492, even after being stratified by age at onset and gender. In addition, we found that no significant differences were detected in the clinical manifestations for gender, age at onset, and onset symptoms between PD patients with AG + GG genotypes and those with AA genotypes. Our study from the mainland China demonstrates that RIT2 rs12456492 do not increase the risk of developing PD. Therefore, more replication studies in additional Chinese population and other cohorts are warranted to further clarify the role of RIT2 rs12456492 in PD susceptibility.
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Proteínas de Unión al GTP Monoméricas/genética , Enfermedad de Parkinson/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Recently, mutations in the coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) gene have been identified in Japanese families with autosomal dominant Parkinson's disease (PD) and two single nucleotide variants (rs10043 and Pro2Leu) increased risk of sporadic PD. The role of CHCHD2 in PD susceptibility in other Asian populations still remains to be clarified. In a large Chinese cohort from mainland China (31 familial PD patients, 1,027 sporadic PD patients, and 1,095 health controls), we examined the association of rs10043 and Pro2Leu variants in CHCHD2 with PD. All subjects were homozygous for rs10043. Moreover, we detected six patients (0.57%, one of the six patients has family history) and three controls (0.27%) with a heterozygous Pro2Leu variant. Though the frequency of Pro2Leu variant was two times higher in PD compared to controls, the difference did not reach significance in genotypic distribution (P = 0.47) or allelic distribution (P = 0.47). However, our meta-analysis in Asian populations revealed that the frequency of Pro2Leu variant was significantly higher in PD patients than in controls (P = 0.0002). Our study suggests that Pro2Leu in CHCHD2 may be a risk factor for PD among Asians. © 2016 Wiley Periodicals, Inc.
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Proteínas Mitocondriales/genética , Enfermedad de Parkinson/genética , Factores de Transcripción/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Pueblo Asiatico/genética , China , Proteínas de Unión al ADN , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas , Genotipo , Humanos , Leucina , Masculino , Persona de Mediana Edad , Proteínas Mitocondriales/sangre , Proteínas Mitocondriales/metabolismo , Mutación , Enfermedad de Parkinson/etiología , Prolina , Factores de Riesgo , Factores de Transcripción/sangre , Factores de Transcripción/metabolismoRESUMEN
PURPOSE: A genome-wide association study (GWAS) has recently identified a novel single nucleotide polymorphism (SNP) rs356182 at SNCA that can modulate the risk of Parkinson's disease (PD) in Caucasian ancestry. The present study was designed to clarify the strength of the association in ethnic Chinese population. METHODS: Using a case-control methodology, we genotyped the SNP rs356182 to investigate the association with risk of PD. A total of 2205 ethnic Han Chinese study subjects comprising 1053 sporadic PD patients (581 males, 472 females) and 1152 controls (604 males, 548 females) were recruited from Mainland China. Additionally, the SHEsis software platform was applied for linkage disequilibrium (LD) analysis between rs356182 and another PD-associated synuclein SNP rs356219 we previously reported. RESULTS: The frequency of SNCA rs356182-G allele was significantly higher in PD group than that in controls (odds ratio (OR)=1.470, 95% confidence interval (CI): 1.284-1.683, P=2.306E-8). Subjects carrying GG/AG genotype had an increased risk compared with the AA carriers (OR=1.162, 95% CI: 1.143-2.274, P=0.006). Among all the genotypes of rs356182, GG genotype showed the strongest association with risk of PD (GG vs. AG/AA, OR=1.620, 95% CI: 1.368-1.919, P=2.001E-8). However, the gender, onset age, disease duration, Hoehn-Yahr stage, UPDRS scores and other clinical features were similar between GG genotype carriers and non-carriers. No LD between rs356182 and rs356219 was found in our population (r(2)=0.016 and D'=0.163). CONCLUSION: Our study firstly demonstrates that SNCA rs356182 variant has an increased risk of susceptibility to PD in Han Chinese population. Further functional analysis is required to determine the role of this SNP in development of PD.
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Predisposición Genética a la Enfermedad , Enfermedad de Parkinson , Polimorfismo de Nucleótido Simple/genética , alfa-Sinucleína/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/etnología , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/etnología , Enfermedad de Parkinson/genética , Adulto JovenRESUMEN
Previous studies identified that polymorphisms RAB7L1/NUCKS1 rs823118, MCCC1 rs12637471 and STK39 rs1955337 to be the risk loci for Parkinson's disease (PD) in a Caucasian population. However, the characteristics of these three polymorphisms in a Han Chinese population from mainland China were unknown. We examined genetic associations of rs823118, rs12637471 and rs1955337 with PD susceptibility in a Han Chinese population of 1016 sporadic PD patients and 1069 controls. We also conducted further stratified analysis according to age at onset and compared the clinical characteristics between minor allele carriers and non-carriers for each locus. In this study, the minor allele frequency (MAF) was significantly different of RAB7L1/NUCKS1 rs823118 (P = 0.003) and MCCC1 rs12637471 (P = 0.008) between cases and controls. Subjects of RAB7L1/NUCKS1 rs823118 with CC+CT genotypes had a decreased risk compared to those with TT genotype (P = 0.001) and this association also can be seen among younger population (<50 years, P = 0.011). For the MCCC1 rs12637471, subjects with GA+GG genotypes had an increased risk compared to those with AA genotype (P = 0.017). However, we did not observe any significant difference in allele and genotype distribution between PD patients and controls for rs1955337 in STK39. In addition, minor allele carriers cannot be distinguished from non-carriers based on their clinical features of the three loci. Our study provides strong support for the susceptibility role of rs823118 and rs12637471 in sporadic PD in a Han Chinese population.
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Pueblo Asiatico/genética , Ligasas de Carbono-Carbono/genética , Predisposición Genética a la Enfermedad/genética , Enfermedad de Parkinson/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas de Unión al GTP rab1/genética , Anciano , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Proteínas de Unión al GTP rabRESUMEN
Large-scale meta-analysis of genome-wide association data has identified six new risk loci (SIPA1L2, INPP5F, MIR4697, GCH1, VPS13C, and DDRGK1) for Parkinson's disease (PD). However, the characteristics of those loci in a Han Chinese population from mainland China are unknown. We examined genetic associations of VPS13C rs2414739, MIR4697 rs329648, GCH1 rs11158026, and SIPA1L2 rs10797576 with PD susceptibility in a Han Chinese population of 1028 sporadic PD patients and 1109 healthy controls. All subjects were genotyped for these loci using the Sequenom iPLEX Assay. We also conducted further stratified analysis according to age at onset and compared the clinical characteristics between minor allele carriers and non-carriers for each locus. However, we did not observe any significant difference in genotype distribution between PD patients and controls for the four loci, even after being stratified by age at onset. Besides, minor allele carriers cannot be distinguished from non-carriers based on their clinical features. Our findings first demonstrated that VPS13C rs2414739, MIR4697 rs329648, GCH1 rs11158026, and SIPA1L2 rs10797576 do not confer a significant risk for PD in Chinese population. Additional replication studies in other populations and functional studies are warranted to better validate the role of the four new loci in PD risk.
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Pueblo Asiatico/genética , Etnicidad/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Variación Genética , Enfermedad de Parkinson/genética , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Sitios Genéticos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Sequence variants in SLC41A1 (solute carrier family 41 member 1) within the PARK16 locus have been reported to be associated with Parkinson's disease (PD). We performed direct DNA sequencing of the SLC41A1 gene in 100 early-onset PD cases. A novel intron variant (NM_173854.5:c.993-90delA) and a known synonymous-coding variant (NM_173854.5:c.339 C>T, causing p.Thr113Thr, rs11240569) were identified in the SLC41A1 gene. Then we genotyped the rs11240569 variant in a total of 2237 Han Chinese comprising of 1063 sporadic PD and 1174 controls to investigate the association with risk of PD, we also conducted further stratified analysis according to age at onset and compared the clinical characteristics of CC + CT subjects with TT subjects. In this study, we confirmed that the C allele of SLC41A1 (rs11240569) polymorphism reduces the risk to develop sporadic PD (P = 0.018). Additionally, subjects with CC + CT genotypes have a reduced risk compared to those with TT genotype (P = 0.022), the association was modestly seen among the younger age group (P = 0.05), but was not significant among the older age group (P = 0.641). Besides, we demonstrated that CC + CT subjects cannot be distinguished from TT subjects based on their clinical features. Our study, the first demonstrates that SLC41A1 (rs11240569) is associated with a lower risk of PD in a Han Chinese population from mainland China.
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Proteínas de Transporte de Catión/genética , Enfermedad de Parkinson/genética , Adulto , Edad de Inicio , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Intrones , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: To investigate the effects of sub-micro emulsion composition on cellular uptake and disposition of incorporated lipophilic drug. METHODS: Sub-micro emulsions containing 10 % oil, 1.2 % lecithin and 2.25 % glycerol were prepared, and the fluorescent agent coumarin 6 was used as a model drug. The effects of oil types, co-surfactants and cationic lipid on uptake and elimination kinetics of 6-coumarin in HeLa cells were studied. The uptake mechanism of sub-micro emulsions was further investigated. RESULTS: Oil type and Tweens had no influence on the cellular uptake. Modifications of surfactants with Span series increased the cellular influx, among which Span 20 with hydrophilic-lipophilic balance (HLB) value of 8.6 was the best enhancer. The intracellular drug level reached up to (46.09 ± 1.98)ng/µg protein which had significant difference with control group [(38.54 ± 0.34)ng/µg protein]. The positively charged emulsions significantly increased the uptake rate constant and elimination rate constant which were 4 times and 1.5 times of those in anionic groups, respectively. The uptake enhancement was also observed in cationic emulsions, cellular concentrations at plateau were (42.73 ± 0.84)ng/µg protein, which was about 3 times of that in anionic emulsions [(15.71 ± 0.74)ng/µg protein], when extracellular drug concentration kept at 100 ng/ml. Cationic emulsions delivered the payload mainly by direct drug transfer to contacted cells, while the negative ones depended on both drug passive diffusion and clathrin-mediated endocytosis of drug containing oil droplets which accounted for 20% of the intracellular drug. CONCLUSION: Interfacial characteristic of sub-micro emulsions such as co-surfactants HLB as well as zeta potentials can influence lipophilic drug both in cellular uptake and elimination.
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Cumarinas/farmacocinética , Tensoactivos/farmacocinética , Tiazoles/farmacocinética , Aniones , Cationes , Emulsiones , Endocitosis , Células HeLa , HumanosRESUMEN
OBJECTIVE: To determine the optimal positive end-expiratory pressure (PEEP) according to inflation and deflation pressure-volume curve (P-V curve) in patients with acute respiratory distress syndrome (ARDS). METHODS: ARDS models were reproduced in 20 dogs, and they were randomly divided into two groups. In both groups, Levenberg-Marquardt iterative algorithm was employed using software to explore parameters fitting with Boltzmann formula, by which the real inflection point of pressure (Pinf d) in deflation limb or lower inflection point pressure (PLip) in inflation limb on P-V curve were defined. For the control group (inflation curve) P-V curve of PLip + 2 cm H(2)O [1 cm H(2)O = 0.098 kPa] was applied as the best PEEP value. In the experimental group (deflation curve) the Pinf d was taken as the best PEEP value. The heart rate (HR), blood pressure (BP), fingertip pulse oxygen saturation [SpO(2)], static lung compliance (Cst), arterial partial pressure of oxygen [PaO(2)] and arterial partial pressure of carbon dioxide [PaCO(2)] were monitored at 0, 2, 6, 12, 24 and 48 hours. RESULTS: Oxygenation index increased significantly both in control and experimental groups. In experimental group, oxygenation index (mm Hg, 1 mm Hg = 0.133 kPa) of 12, 24 and 48 hours was respectively significantly higher than that of the control group (12 hours: 177.63 ± 8.94 vs. 165.60 ± 8.90, 24 hours: 194.19 ± 10.67 vs. 168.70 ± 10.60, 48 hours: 203.15 ± 13.21 vs. 171.26 ± 9.21, all P < 0.01). Cst [ml/cm H(2)O] at 2, 6, 12, 24 and 48 hours was respectively higher than that of the control group (2 hours: 41.00 ± 4.17 vs. 36.20 ± 3.90, 6 hours: 44.00 ± 4.65 vs. 36.88 ± 3.39, 12 hours: 46.92 ± 5.47 vs. 37.92 ± 3.10, 24 hours: 42.83 ± 8.97 vs. 37.92 ± 3.09, 48 hours: 42.64 ± 9.04 vs. 37.97 ± 2.98, P < 0.05 or P < 0.01). CONCLUSION: Determining optimal PEEP for ARDS with deflation P-V curve was better than that of inflation curve.
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Oxígeno/metabolismo , Respiración con Presión Positiva , Síndrome de Dificultad Respiratoria/fisiopatología , Animales , Perros , Rendimiento Pulmonar , Curvas de Flujo-Volumen Espiratorio Máximo , Síndrome de Dificultad Respiratoria/metabolismo , Volumen de Ventilación PulmonarRESUMEN
OBJECTIVE: To investigate the surgical outcomes after on transumbilical laparoscopic pull-through procedure for pediatric hypoganglionosis(HYP). METHODS: Twelve children with HYP had received transumbilical laparoscopic pull-through procedure from June 2009 to June 2010. Specially designed curved and elongated laparoscopic instruments were used during the procedures. All the patients were followed up over 10 months. Data were collected and analyzed. The diagnosis of hypoganglionsis was pathologically confirmed. RESULTS: No conversions to laparotomy or traditional laparoscopic surgery were required and there were no damages to the abdominal blood vessels, intestine, ductus deferens, or ureters. The average duration of operation was 140 min. The mean intraoperative blood loss was 45 ml. The mean length of specimen was 40 cm. Postoperatively there were no complications such as anastomotic leak, anastomotic stricture, constipation, seepage, or fecal in continence. The average hospital stay after surgery was 9 days. During 10 to 22 months of follow-up(median 16 months), no postoperative recurrence was noticed. No obvious scar was seen 1 months after surgery. CONCLUSION: It is safe and effective for children with hypoganglionosis to undergo transumbilical laparoscopic pull-through procedure.
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Enfermedad de Hirschsprung/cirugía , Laparoscopía/métodos , Ombligo/cirugía , Canal Anal/cirugía , Niño , Preescolar , Colon/cirugía , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
OBJECTIVE: To compare the differences in antitumor activity between cisplatin (CDDP)-loaded liposomes and nanoparticles in vitro. METHODS: CDDP-gelatin nanoparticles (GPs-Pt) and CDDP-liposomes with similar size, zeta potential, drug loading efficiency and in vitro release property were prepared. The uptake in A549 cells and elimination kinetics were evaluated and antitumor activity was determined by MTT test. The internalization pathways of nanocarriers were studied with inhibitors. RESULTS: Internalization of two nanocarriers was clathrin and actin dependent. Pt accumulation delivered by GPs-Pt was significantly higher than that of liposomes. However, the results of kinetic analysis showed that liposomes had longer cellular retention, and the MRT and AUC were 3 times and twice of GPs-Pt, respectively. The IC(50) of liposomes was significantly lower than GPs-Pt. The values were 2.94±0.21 and 20.70±1.05 µg/ml, respectively. CONCLUSION: Nanocarriers with similar pharmaceutical parameters can induce differences in cellular internalization and elimination, which influence the antitumor activity eventually. Compared with gelatin nanoparticle, liposome is preferable for cisplatin delivery.
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Cisplatino/farmacología , Portadores de Fármacos , Liposomas , Nanopartículas , Adenocarcinoma/patología , Antineoplásicos/farmacología , Línea Celular Tumoral , Cisplatino/farmacocinética , Humanos , Neoplasias Pulmonares/patologíaRESUMEN
Modern drug delivery system demands high therapeutic efficacy and low toxicity which depends on efficient intracellular transportation of therapeutics to specific organisms, cells, even targeted organelles such as cytosol, nucleus, mitochondria, lysosome and endoplasmic reticulum. Intracellular barriers which prevent drug molecules accessing to their targets mainly include cell membrane, lysosomal degradation and the endomembrane system. Nanocarriers can preserve the bioactivities of protein, enzyme and DNA, and also they are easy to be modified and functionalized. In this paper, we summarized the intracellular fate of nanocarriers, especially how to bypass intracellular barriers and then target cytosol, nucleus, mitochondria, lysosome and endoplasmic reticulum by pharmaceutical modifications.
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Portadores de Fármacos , Nanopartículas , Orgánulos , Animales , Sistemas de Liberación de Medicamentos , HumanosRESUMEN
The goal of this research was to prepare a kind of hydrophilic sustained release microspheres of interferon-alpha (IFN-alpha), alginate-chitosan microspheres (ACM) of IFN, and investigate its pharmacokinetics in mice. Alginate microspheres of IFN-alpha were first prepared by an emulsion method and further incubated in chitosan to form IFN-ACM. The influences of isopropanol, bovine serum albumin (BSA), and pH adjustment by isoelectric point of IFN were studied. The optimized IFN-ACM was obtained with smooth and round morphology, size of 2.18 +/- 0.43 microm and entrapment efficiency of 40%. All the concentrations of IFN-alpha were determined by IFN assay kits. Finally the pharmacokinetics of IFN-ACM suspension was studied in ICR mice by intramuscular (I.M.) routes. Compared with IFN solution, C(max) of IFN-ACM reduced 2.3-fold, and time to achievement of maximum serum concentrations (T(max)) increased 4-fold. Meanwhile the area under the concentration-time curve (AUC) was the same as that of solution. The concentration-time profiles presented the prolonged serum levels of IFN from IFN-ACM.
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Portadores de Fármacos , Interferón-alfa/farmacocinética , Microesferas , Alginatos/química , Alginatos/metabolismo , Animales , Cápsulas/química , Cápsulas/farmacocinética , Bovinos , Quitosano/química , Quitosano/metabolismo , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Femenino , Ácido Glucurónico/química , Ácido Glucurónico/metabolismo , Ácidos Hexurónicos/química , Ácidos Hexurónicos/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Ratones , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
AIM: To prepare cells scaffolds with the characteristics of sustained release of proteins. METHODS: Chitosan scaffolds was prepared by freeze-drying. Porosity and water content of scaffolds were determined. Bovine serum album (BSA) was selected as a model protein. Poly (lactic-co-glycolic acid) (PLGA) microspheres were prepared by double emulsion solvent evaporation and encapsulated into chitosan scaffolds. The morphology of PLGA microspheres and various scaffolds were observed using scanning electron microscope. Release behavior of BSA from various chitosan scaffolds was investigated. RESULTS: The chitosan scaffold represents porous. At the -70 degrees C of quenching temperature, the porosity and water content of chitosan scaffolds were 78.6% +/- 1.5% and 85.1% +/- 6.2%, respectively. PLGA microspheres can be uniformly encapsulated into scaffolds without any morphology change. Significant sustained release of BSA from PLGA microspheres encapsulated into scaffolds was obtained. The cumulative release at 168 h was only 33.5%, while that of BSA from chitosan scaffolds at 24 h was above 90%. The release behavior can be controlled by adjusting the amount of chitosan in scaffolds and the type of PLGA. CONCLUSION: The novel chitosan scaffolds encapsulating PLGA microspheres proved to be a promising cells scaffolds with controlling the release of growth factors in tissue engineering.
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Quitosano/administración & dosificación , Ácido Láctico , Ácido Poliglicólico , Polímeros , Albúmina Sérica Bovina/metabolismo , Ingeniería de Tejidos/métodos , Quitosano/química , Portadores de Fármacos , Liofilización/métodos , Ácido Láctico/química , Microesferas , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/químicaRESUMEN
AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and microvascular density (MVD) count in pediatric malignant liver tumor and their clinical significances. METHODS: Fourteen children with malignant liver tumors including seven hepatocellular carcinomas (HCCs), five hepatoblastomas, one malignant mesenchymoma and one rhabdomyosarcoma were studied. Twelve adult HCC samples served as control group. All samples were examined with streptavidin-biotin peroxidase (SP) immunohistochemical staining for VEGF expression and MVD count. RESULTS: VEGF positive expression in all pediatric malignant liver tumors was significantly higher than that in adult HCC (0.4971+/-0.14 vs 0.4027+/-0.03, P<0.05). VEGF expression in pediatric HCC group was also markedly higher than that in adult HCC group (0.5665+/-0.10 vs 0.4027+/-0.03, P<0.01) and pediatric non-HCC group (0.5665+/-0.10 vs 0.4276+/-0.15, P<0.05). The mean value of MVD in pediatric malignant liver tumors was significantly higher than that in adult HCC (33.66+/-12.24 vs 26.52+/-4.38, P<0.05). Furthermore, MVD in pediatric HCC group was significantly higher compared to that in adult HCC group (36.94+/-9.28 vs 26.52+/-4.38, P<0.05), but there was no significant difference compared to the pediatric non-HCC group (36.94+/-9.28 vs 30.37+/-14.61, P>0.05). All 7 children in HCC group died within 2 years, whereas the prognosis in pediatric non-HCC group was better, in which two patients survived more than 5 years. CONCLUSION: Children with malignant liver tumors, especially with HCC, may have extensive angiogenesis that induces a rapid tumor growth and leads to a poor prognosis.
Asunto(s)
Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/patología , Neovascularización Patológica/patología , Adolescente , Carcinoma Hepatocelular/mortalidad , Niño , Preescolar , Femenino , Hepatoblastoma/irrigación sanguínea , Hepatoblastoma/mortalidad , Hepatoblastoma/patología , Humanos , Lactante , Neoplasias Hepáticas/mortalidad , Masculino , Mesenquimoma/irrigación sanguínea , Mesenquimoma/mortalidad , Mesenquimoma/patología , Microcirculación , Neovascularización Patológica/metabolismo , Neovascularización Patológica/mortalidad , Pronóstico , Rabdomiosarcoma/irrigación sanguínea , Rabdomiosarcoma/mortalidad , Rabdomiosarcoma/patología , Tasa de Supervivencia , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
AIM: To study the long-term therapeutic effect of "heart-shaped" anastomosis for Hirschsprung's disease. METHODS: From January 1986 to October 1997, we performed one-stage "heart-shaped" anastomosis for 193 patients with Hirschsprung's disease (HD). One hundred and fifty-two patients were followed up patients (follow-up rate 79%). The operative outcome and postoperative complications were retrospectively analyzed. RESULTS: Early complications included urine retention in 2 patients, enteritis in 10, anastomotic stricture in 1, and intestinal obstruction in 2. No infection of abdominal cavity or wound and anastomotic leakage or death occurred in any patients. Late complications were present in 22 cases, including adhesive intestinal obstruction in 2, longer anal in 5, incision hernia in 2, enteritis in 6, occasional stool stains in 7 and 6 related with improper diet. No constipation or incontinence occurred in any patient. CONCLUSION: The early and late postoperative complication rates were 7.8% and 11.4% respectively in our "heart-shaped anastomosis" procedure. "Heart-shaped" anastomosis procedure for Hirschsprung's disease provides a better therapeutic effect compared to classic procedures.