Type of bony involvement predicts genomic subgroup in sphenoid wing meningiomas

Journal of Neuro-Oncology - As sphenoid wing meningiomas (SWMs) are associated with varying degrees of bony involvement, we sought to understand potential relationships between genomic subgroup and...     

紫雪丹的质量控制

目的:建立紫雪丹的质量控制标准。方法:采用薄层色谱法对甘草、木香进行定性鉴别;采用气相色谱法对龙脑进行含量测定。结果:定性鉴别阴性无干扰,分离度高;龙脑在100μg·m L-1~800μg·m L-1(r=0.9996)范围内线性关系良好,加样回收率为100.79%,RSD为2.5%(n=6)。结论:方法可用于紫雪丹的质量控制。     

pfcrt Polymorphism and the spread of chloroquine resistance in Plasmodium falciparum populations across the Amazon Basin

The widespread occurrence of drug-resistant malaria parasites in South America presents a formidable obstacle to disease control in this region. To characterize parasite populations and the chloroquine-resistance profile of Plasmodium falciparum in the Amazon Basin, we analyzed a DNA segment of the pfcrt gene, spanning codons 72-76, and genotyped 15 microsatellite (MS) markers in 98 isolates from 6 areas of Brazil, Peru, and Colombia where malaria is endemic. The K76T mutation, which is critical for chloroquine resistance, was found in all isolates. Five pfcrt haplotypes (S[tct]MNT, S[agt]MNT, CMNT, CMET, and CIET) were observed, including 1 previously found in Asian/African isolates. MS genotyping showed relatively homogeneous genetic backgrounds among the isolates, with an average of 3.8 alleles per marker. Isolates with identical 15-loci MS haplotypes were found in different locations, suggesting relatively free gene flow across the Amazon Basin. Allopatric isolates carrying SMNT and CMNT haplotypes have similar genetic backgrounds, although parasites carrying the CIET haplotype have some exclusive MS alleles, suggesting that parasites with CIET alleles were likely to have been introduced into Brazil from Asia or Africa. This study provides the first evidence of the Asian pfcrt allele in Brazil and a detailed analysis of P. falciparum populations, with respect to pfcrt haplotypes, in the Amazon Basin.     

Genetic variants of interferon-stimulated genes and IL-28B as host prognostic factors of response to combination treatment for chronic hepatitis C

Chronic hepatitis C (CHC) is a worldwide health problem that is highly related to liver fibrosis, cirrhosis, and hepatocellular carcinoma. The achievement of response to the current standard of care-pegylated interferon plus ribavirin-has recently been described to be associated with single-nucleotide polymorphisms (SNPs) near the IL-28B gene. Additionally, baseline expression levels of genes involved in interferon (IFN)-stimulated genes (ISGs) have been found to be related to treatment outcome. In the present study, 285 patients were genotyped for 63 SNPs within genes of the IFN signaling pathway (IPGs) and ISGs. Two ISG polymorphisms-OASL rs12819210 (odds ratio (OR)=2.1, P=0.03) and IFIT1 rs304478 (OR=2.5, P=0.01)-were found to be independent predictive factors of sustained virological response (SVR) after adjusting for other clinical covariates. Furthermore, the predictive value of IL-28B SNP was notably improved by simultaneous genotyping of rs12819210 and rs304478, particularly in patients with the worst prognosis (viral genotype 1, area under the curve (AUC)=0.74). In conclusion, ISG SNPs could constitute a valuable tool for individualizing CHC therapy.     

Influence of pressure control levels on the pulse pressure variations: an animal study using healthy piglets

Pulse pressure variation (PPV) is a promising predictor for volume responsiveness. However, recent studies have criticized its validity during small tidal volume (TV) ventilation. The present study evaluated the influence of pressure control level (PCL) on PPV. Six anesthetized healthy piglets simulating hemorrhagic shock underwent five stages of intravascular volume status change. Each stage comprised four cycles of PCL manipulation. In each cycle, five different PCLs were applied in random order. Among 600 arterial pressure tracings obtained during PCL manipulations, 26 tracings were excluded because of signal artifact or ectopic beats. For the remaining 574 tracings, the percentage of normal beats among total recorded beats in each tracing was 99.80% ± 0.85%. When manipulating PCL causing an abrupt change within -16 ～ +8 cmH(2)O, the PPV responded rapidly and stabilized within 60 s after manipulation. With higher increment in PCL (+12 ～ +16 cmH(2)O), it required 90 s for PPV to stabilize. Under each cycle of PCL manipulation, the PPVs are linearly correlated to the PCL (r = 0.84 ± 0.21) and TV (r = 0.83 ± 0.22). The PPV as well as the slopes of the trend lines decreased from hypovolemic stages toward hypervolemic stages. Pulse pressure variation responds rapidly to change in ventilator setting and is linearly correlated with the PCL and TV. These characteristics may have important applications in critical care to improve the interpretation of PPV in accord to different ventilator settings.     

Novel powder formulations for controlled delivery of poorly soluble anticancer drug: application and investigation of TPGS and PEG in spray-dried particulate system.

Biodegradable poly (lactic-co-glycolic acid) (PLGA), D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) and/or polyethylene glycol (PEG) were combined as pharmaceutical excipient to fabricate microparticles containing sparingly soluble drug paclitaxel by spray-drying technique with successful achievement. The effect of formulation variety on particle morphology, surface composition, thermal property, drug entrapped capability, and drug release profile was investigated. The result indicated that the use of the appropriate mixtures of PLGA, TPGS and/or PEG produced paclitaxel-loaded microparticles characterised by acceptable pharmaceutical properties. Atomic force microcopy (AFM) and scanning electron microscopy (SEM) showed that the produced microparticles were spherical in shape with dimples or pores. The particle size ranged from 0.88 to 2.44 microm with narrow distribution. The combination of TPGS and PEG in the formulation resulted in a narrow particle size distribution in general although the influence of the formulation on the particle size was not significant. Differential scanning calorimetry (DSC) study implied that all those components in consideration were compatible well in the blend formulation systems. The paclitaxel entrapped in the particles existed in an amorphous or disordered-crystalline status in the matrices and was independent of the PLGA/TPGS/PEG ratio. X-ray photoelectron spectroscope (XPS) analysis revealed that after incorporation the particle's surface was dominated with PLGA due to its hydrophobic property. The formulation variety had an important impact on the drug release that was reduced with the presence of large fraction of TPGS resulting from a strong hydrophobic interaction between various matrix materials and the drug inside the particle. A zero order release could be yielded by optimising the ratio of PLGA/TPGS/PEG. The combination of PLGA/TPGS/PEG as safe pharmaceutical excipient to formulate particulate delivery system is beneficial in improving the pharmaceutical properties for further powder dosage application.