Preparation and pharmacokinetics of honokiol long-circulating liposomes / 中草药

Objective To optimize the preparation process of honokiol long-circulating liposomes (HLCL) and study the in vitro and in vivo release. Methods An orthogonal experiment was designed to optimize the composition of HLCL using entrapment efficiency as evaluation indicator. The liposome surface morphology was observed by transmission electron microscope (TEM), and the liposome release in vitro was studied by dialysis method. The concentration of honokiol in rat plasma was determined by the established LC-MS/MS method, and the differences in pharmacokinetic parameters were compared after honokiol and HLCL (20 mg/kg) were orally administered to SD male rats, respectively. Results The optimal composition of HLCL was 8:1:1 for soya phosphatidyl choline-cholesterol-mPEG2000-DSPE, and 1:10 for honokiol-liposome materials with the ultrasonic time of 12 min. Under the optimized conditions, HLCL was sphere with mean particle size of 121.5 nm and mean Zeta potential of -30.8 mV, the encapsulation efficiency and drug-loading content was 84.7% and 10.4%, respectively. In vitro release results showed that the liposomes could be gently and slowly release with the 24 h cumulative release rate at pH 1.2 and pH 6.9 dissolve medium of 80% and 71%, respectively. Based on the pharmacokinetic results, Cmax, tmax, and t1/2 were (23.29 ± 11.76) ng/mL, (0.13 ± 0.05) h and (10.59 ± 5.72) h for HLCL, and (79.34 ± 56.32) ng/mL, (0.30 ± 0.07) h and (4.44 ± 3.14) h for honokiol, respectively. There was no significant difference about the AUC0-∞ following oral administration of honokiol and HLCL at isodose honokiol (20 mg/kg). Conclusion Compared with honokiol, HLCL was released gently and slowly in vitro, absorpted rapidly and eliminated slowly in vivo.

Functional analysis of a novel SCN5A mutation G1712C identified in Brugada syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>To elucidate the molecular and electrophysiological mechanisms of Brugada syndrome through functional analysis of a novel SCN5A gene mutation G1712C.</p><p><b>METHODS</b>A recombinant plasmid pRc<CMV-hH1 containing the mutant human cardiac sodium channel α subunit (hH1) cDNA was constructed using in vitro PCR-based site-directed mutagenesis technique. LipofectamineTM 3000 was used to transfect the plasmid DNA into HEK293 cell line to induce stable expression of Nachannel β1-subunit, and the positive colonies were selected by screening with G418.The standard liposome method was used to transiently transfect HEK293 cells with either the wild-type or mutant Nachannel subunits (hH1 and mhH1, respectively), and the macroscopic Nacurrents were recorded using whole-cell patch-clamp technique. Data acquisition and analysis, generation of voltage commands and curve fitting were accomplished with EPC-10, PatchMaster and IGOR Pro 6.0.</p><p><b>RESULTS</b>An HEK293 cell line that stably expressed Nachannel β1-subunit was successfully established. After transient transfection with the WT subunit, large Nacurrents were recorded from the stable β1-cell line. Transient transfection with the G1712C subunit, however, did not elicit a Nacurrent in the cells.</p><p><b>CONCLUSION</b>Compared with normal Nachannel, the wild-type channel exhibits a similar sodium current. The characteristic kinetics of sodium channel of WT-hH1 was identical to that in normal cardiac muscle cell, and the missense mutation (G1712C) in the P-loop region of the domain IV may have caused the failure of sodium channel expression.</p>

The quality status of anesthetic units used in Shanghai and the supervision countermeasures / 中国医疗器械杂志

Based on the testing results of samples, this article represents the safety status of anesthetic units used in Shanghai medical institutions. In order to guarantee the safety and efficacy of the anesthetic devices, the medical institutions should set up some effective management systems, the related government departments should immediately perfect their administration system and bring in the market-operated professional maintenance organizations.

Expression of neutrophil adhesion molecule CD11b as an early diagnostic marker for neonatal sepsis / 中华儿科杂志

<p><b>OBJECTIVE</b>Neonatal sepsis is a common disease and the sepsis-related mortality rate is still high. Until now, there has no ideal diagnostic marker to early identify neonatal sepsis. Expression of neutrophil adhesion molecule CD(11b) was showed as the earlier reaction to the infection/inflammation, and may be applied as an early diagnostic marker for sepsis. This study was to investigate this antigen for early diagnosis of neonatal sepsis related to bacterial infection.</p><p><b>METHODS</b>According to clinical symptoms, signs and four indices (WBC, PLT, plasma CRP and ratio of I/T), fifty-one neonates with established or suspected sepsis were allocated retrospectively into two groups of sepsis [n = 23, gestational age of (38.3 +/- 2.4) weeks, postnatal age of (12.7 +/- 8.8) days, body weight: (3.1 +/- 0.8) kg] and suspected sepsis [n = 28, gestational age of (38.8 +/- 1.6) weeks, postnatal age of (11.7 +/- 7.3) days, body weight: (3.3 +/- 0.6) kg]. Fifteen healthy neonates were served as controls [gestational age: (38.5 +/- 1.4) weeks, postnatal age: (8.2 +/- 5.5) days, body weight: (3.3 +/- 0.3) kg]. CD(11b) was quantified with the whole blood flow cytometry and direct immunofluorescence technique.</p><p><b>RESULTS</b>The expressions of neutrophil CD(11b) in neonates with sepsis and suspected sepsis were (320 +/- 189) MFI and (456 +/- 213) MFI, respectively, which was lower than that of controls [(1,090 +/- 338) MFI, t = -9.01 and -7.56, respectively; P < 0.001]. The expression of CD(11b) was lower in neonates with sepsis than that with suspected sepsis (t = -2.39, P < 0.05). The expression of CD(11b) in neonates with CRP >or= 30 mg/L was (211 +/- 164) MFI, which was lower than those with CRP < 30 mg/L [(505 +/- 265) MFI, t = 2.64, P < 0.05]. The detection of CD(11b) (<or= 600 MFI) for suspected sepsis showed a sensitivity of 86.3%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 68.2%. The positive rate of CD(11b) detection was 86.3%, which was higher than the blood culture test (17.6%, chi(m)(2) = 31.2, P < 0.05).</p><p><b>CONCLUSION</b>The expression of CD(11b) in neonatal sepsis presented with a down-regulation and, the decreased CD(11b) expression might be related to the severity of infections. For the neonatal sepsis the serial measurements of neutrophil CD(11b) expression with the whole blood flow cytometry seemed feasible and reliable in the early diagnosis, evaluation of infection severity and observation of therapy reactions.</p>