Population pharmacokinetic study of tacrolimus in pediatric patients with primary nephrotic syndrome / 药学学报

Tacrolimus is commonly used in the treatment for the refractory primary nephrotic syndrome (PNS) in the pediatric patients. Data were retrospectively obtained from 100 children with 357 tacrolimus trough concentrations in our center between May 2010 and March 2016. Information of age, sex, body weight, drug dose, co-therapy medications, laboratory tests and sampling time were collected. The population pharmacokinetic model was developed using nonlinear mixed effect modeling (NONMEM) software. A one-compartment model with first-order absorption and elimination best described the data. The population estimate of apparent clearance (CL/F) and apparent volume of distribution (V/F) was 6.54 L·h-1 and 86.2 L, respectively. Body weight (WT, kg), daily dose of tacrolimus (DD, mg·day-1) and co-therapy azole antifungal agent have a significant impact on the CL/F. The final PPK model of CL/F was:CL/F=6.54×((WT)/25)K×((DD)/1.5)0.293×0.657Azole,K=(WT-30.9)/(WT-30.9+10.4-30.9). When combined with azole antifungal agents, Azole was 1, whereas vice versa was 0. This is the first PPK study of tacrolimus conducted in pediatric patients with PNS, which may facilitate individualized drug therapy of tacrolimus.

Association of drug resistance of Mycoplasma pneumoniae with DNA load and genotypes in children with Mycoplasma pneumoniae pneumonia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the association of drug resistance of Mycoplasma pneumoniae (MP) with DNA load and genotypes in children with MP pneumonia.</p><p><b>METHODS</b>A total of 230 children who were hospitalized and diagnosed with MP pneumonia between January 2012 and December 2016 were enrolled. Throat swabs were collected from the 230 children, and a rapid drug sensitivity assay was used to determine the sensitivity of clinical isolates of MP to nine commonly used antibacterial agents. Quantitative real-time PCR was used to measure MP-DNA load in throat swabs. PCR sequencing was used to determine the genotype of 2063 locus of the MP 23S rRNA V domain.</p><p><b>RESULTS</b>Of the 230 children, 86 (37.4%) had genotype A in 2063 locus, 134 (58.3%) had genotype G, 8 (3.5%) had genotype C, and 2 (0.9%) had genotype T. Mutant strains (genotype G+C+T) had a significantly higher MP-DNA load than wild-type strains (genotype A) (P<0.05). The strains resistant to erythromycin, azithromycin, clarithromycin, and clindamycin had a significantly higher MP-DNA load than non-resistant strains (P<0.05). MP had a high drug resistance rate to macrolide antibiotics. More than 60% of the cases with resistance to macrolides were found to have A2063G mutations. MP was rarely resistant to quinolones (less than 2%).</p><p><b>CONCLUSIONS</b>Mutations in 2063 locus of the MP 23S rRNA V domain may result in the resistance of MP to macrolides and the change in DNA load and can be used as a basis for selecting drugs for MP.</p>

Application of Mycoplasma pneumoniae antibody and load index in the diagnosis of Mycoplasma pneumoniae pneumonia in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the role of Mycoplasma pneumoniae (MP) load and antibody measurements in the diagnosis of MP pneumonia.</p><p><b>METHODS</b>A total of 115 children with MP pneumonia and 400 healthy children were enrolled. The MP load and total antibody level were measured at different stages, and the MP load index (MPLI) was calculated.</p><p><b>RESULTS</b>The cut-off value of MPLI for MP infection was 6.12. MPLI and total antibody titer increased during the course of the disease, while MP-DNA decreased rapidly. Within the same time of blood collection, the group with a higher MP load had a significantly higher total antibody titer than the group with a lower MP load (P<0.05). Within 2 weeks of the course of the disease, the negative antibody group had a significantly higher MPLI than the positive antibody group (P<0.05).</p><p><b>CONCLUSIONS</b>MPLI provides a standardized quantitative value of MP-DNA and plays an important role in the early diagnosis of MP infection.</p>

Association between CHI3L1 SNPs and susceptibility to childhood asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the association between CHI3L1 single nucleotide polymorphisms (SNPs) and the susceptibility to childhood asthma.</p><p><b>METHODS</b>A total of 316 children diagnosed with asthma between January 2011 and October 2013 and 297 healthy children were selected as asthma group and control group respectively. Peripheral blood samples were collected from all subjects. Chemiluminescence and flow cytometry were applied to measure total IgE level and the percentage of eosinophils. ELISA was used to measure YKL-40 level. Genomic DNA was extracted from peripheral blood hemocytes, and the genotype and allele frequencies at CHI3L1 SNPs rs4950928, rs10399805, and rs883125 were determined by MALDI-TOP mass spectrometry.</p><p><b>RESULTS</b>The total IgE and YKL-40 levels were significantly higher in the asthma group than in the control group (P<0.05), while the percentage of eosinophils showed no significant difference between the two groups (P>0.05). The frequency of GG genotype at rs883125 in the asthma group was significantly higher than that in the control group (P<0.05). For rs4950928, the asthma group had a significantly lower frequency of CC genotype (P<0.05) but a significantly higher frequency of CG genotype (P<0.05) compared with the control group. In the asthma group, the patients with GG and CG genotypes at rs4950928 had significantly increased total IgE and YKL-40 levels compared with those with CC genotype at this locus (P<0.05).</p><p><b>CONCLUSIONS</b>YKL-40 is a potential molecular biomarker for the primary diagnosis of childhood asthma. CHI3L1 SNPs rs4950928 and rs883125 may be associated with childhood asthma. G allele at rs4950928 may increase the risk of childhood asthma.</p>

Changes of plasma cardiotrophin-1 levels in neonates with myocardial ischemic injury / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the changes and significance of plasma cardiotrophin-1 (CT-1) in neonates with hypoxic-ischemic encephalopathy (HIE) complicated by myocardial ischemic injury.</p><p><b>METHODS</b>Forty-five neonates with HIE (15 mild cases, 24 moderate cases and 6 severe cases) were enrolled and divided into two subgroups based on the presence of myocardial injury (n=19) and not (n=26). Twenty healthy neonates were used as the control group. Plasma CT-1 levels were measured using double-antibody sandwich enzyme immunoassay method. Serum creatinine kinase MB (CK-MB) and cardiac troponin I (CTnI ) levels were also measured.</p><p><b>RESULTS</b>Plasma CT-1 levels in the mild HIE (169±20 pg/mL) and moderate/severe HIE subgroups (287±44 pg/mL) were significantly higher than those in the control group (30±8 pg/mL), and plasma CT-1 levels were associated with the severity of HIE (P<0.01). Plasma CT-1 levels were positively correlated with serum CK-MB and CTnI levels in neonates with HIE in the acute phase (r=0.565 and 0.621 respectively; P<0.01). Plasma CT-1 levels in neonates with myocardial injury were significantly higher than those without myocardial injury (249 ±35 pg/mL vs 177±26 pg/mL; P<0.01). Plasma CT-1 levels were significantly reduced in neonates with myocardial injury in the convalescent phase (157±19 pg/mL) compared with those in the acute phase (249±35 pg/mL; P<0.01).</p><p><b>CONCLUSIONS</b>Detection of plasma CT-1 levels may be useful in the diagnosis of myocardial ischemic injury and the severity evaluation of HIE.</p>

ILs-HPLC simultanesous determination of five alkaloids in phellodenddri chinensis cortex / 中国中药杂志

A RP-HPLC method was established for simultaneous determination of phellodendrine hydrochloride (PH1), magnoflorine hydrochloride (MH), jatrorrhizine hydrochloride (JH), palmatine hydrochloride (PH2) and berberine hydrochloride (BH) in Phellodendri Chinensis Cortex by using ionic liquids as mobile phase additives. The separation was performed on a Kromasil C18 (4.6 mm x 250 mm, 5 μm) coupled with ultraviolet (UV) detection. The effect of extraction solvent, detection wavelength, length of alkyl chain on different imidazolium ionic liquids and concentration of ionic liquids on the separation and determination of alkaloids were investigated. Ionic liquid, [BMIm] BF4, can obviously improve the resolution and peak shape. This ILs-HPLC method is simple, rapid, and reliable, which can be used for determination of alkaloids in Phellodenddri Chinensis Cortex.

Determination of protein binding rate of oleanolic acid in human plasma and serum albumin / 药学学报

A LC-MS method was established for the determination of the protein binding rates of oleanolic acid in human plasma and serum albumin. The equilibrium dialysis combined with LC-MS to determine the total concentration in plasma and free drug concentration of oleanolic acid was carried out. The human plasma protein binding rates of oleanolic acid at three concentrations were 79.6%, 81.9% and 63.3%, respectively. The human serum albumin protein binding rates of oleanolic acid at three concentrations were 53.5%, 56.6% and 47.7%, respectively. The method is shown to be simple, accurate, sensitive and specific for the determination of biological samples. The protein binding rates in human plasma and serum albumin were of high strength.