生姜炮制成干姜前后挥发油透皮吸收促进作用的比较研究

目的 比较生姜炮制成干姜前后挥发油透皮吸收促进作用及成分的变化。方法 将生姜炮制成干姜前后提取挥发油，皮肤电阻动力学实验和体外布洛芬透皮实验比较二者的促渗能力，ATR-FTIR红外分析挥发油透皮促渗主要机制，皮肤细胞毒性实验比较了生姜和干姜挥发油的细胞毒性，GC-MS分析成分变化。结果 干姜挥发油的透皮吸收促进作用显著优于生姜挥发油，其透皮促渗机制主要为对皮肤角质层脂质的萃取，而生姜和干姜挥发油的皮肤细胞毒性均显著低于化学促渗剂氮酮，炮制后干姜挥发油的倍半萜类成分比例高于生姜挥发油，透皮后干姜挥发油组皮内的倍半萜类成分比例也高于生姜挥发油组。结论 炮制后的干姜挥发油的透皮吸收作用优于生姜挥发油，验证了中药挥发油透皮吸收促进剂存在"热者易效"的规律。     

Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review

Bacteriophages are not forgotten viruses anymore: scientists and practitioners seek to understand phage pharmacokinetics in animals and humans, investigating bacteriophages as therapeutics, nanocarriers or microbiome components. This review provides a comprehensive overview of factors that determine phage circulation, penetration, and clearance, and that in consequence determine phage applicability for medicine. It makes use of experimental data collected by the phage community so far (PubMed 1924-2016, including non-English reports), combining elements of critical and systematic review. This study covers phage ability to enter a system by various routes of administration, how (and if) the phage may access various tissues and organs, and finally what mechanisms determine the courses of phage clearance. The systematic review method was applied to analyze (i) phage survival in the gut (gut transit) and (ii) phage ability to enter the mammalian system by many administration routes. Aspects that have not yet been covered by a sufficient number of reports for mathematical analysis, as well as mechanisms underlying trends, are discussed in the form of a critical review. In spite of the extraordinary diversity of bacteriophages and possible phage applications, the analysis revealed that phage morphology, phage specificity, phage dose, presence of sensitive bacteria or the characteristics of treated individuals (age, taxonomy) may affect phage bioavailability in animals and humans. However, once phages successfully enter the body, they reach most organs, including the central nervous system. Bacteriophages are cleared mainly by the immune system: innate immunity removes phages even when no specific response to bacteriophages has yet developed.     

Near‐infrared photoimmunotherapy through bone

Near‐infrared photoimmunotherapy (NIR‐PIT) is a molecularly targeted cancer phototherapy that is based on injecting a conjugate of a silicon‐phthalocyanine derivative, IRdye 700DX (IR700), and a monoclonal antibody that targets an expressed antigen on the cancer cell surface. Subsequent local exposure to NIR light results in the rapid and highly selective immunogenic cell death of targeted cancer cells. Because many cancers grow in bones through which light does not penetrate well, the goal of this study was to determine if NIR‐PIT can effectively treat cancers in bone. A bovine rib was used as a bone sample. Because the sample’s NIR light transmittance was shown to be approximately 4.52% in preliminary tests, it was hypothesized that a maximum radiation dosage of 128 and 1500 J/cm² would be sufficient to induce cell death in in vitro target cells and in vivo mouse tumor models, respectively. Cell viability was measured through bioluminescence studies comparing relative luciferase activity, as well as a cytotoxicity assay. In the in vitro model, tumor cell viability was significantly decreased after 64 and 128 J/cm² NIR light irradiation through the bone. An in vivo mouse tumor model also showed that 1500 J/cm² NIR light irradiation through the bone significantly reduced tumor viability at both 24 and 48 hours posttreatment compared to the control group (P = .026 and .040 respectively). Therefore, despite limitations in light transmission, NIR‐PIT nevertheless is capable of effectively treating cancers within bone.     

Simultaneous determination of LY3214996, abemaciclib,and M2 and M20 metabolites in human plasma,cerebrospinal fluid,and brain tumor by LC-MS/MS

A sensitive and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established for the quantification of total and unbound concentrations of LY3214996, an extracellular signal-regulated kinase inhibitor; abemaciclib, a cyclin-dependent kinase 4/6 inhibitor; and abemaciclib active metabolites, M2 and M20, in human plasma, brain tumor, and cerebrospinal fluid samples. The method was validated over a concentration range of 0.2–500 nM within a total run time of 3.8 min using isocratic elution on a Kinetex™ F₅ column. Detection was performed on a Sciex QTRAP 6500+ mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization. The intra- and inter-batch accuracy as well as the precision of the method for all matrices was within ±20% and ≤20% at the lower limit of quantification, and within ±15% and ≤15% for other quality control levels for all analytes. The unbound fractions of drugs and metabolites in spiked and patient samples were determined using an optimized equilibrium dialysis. The validated method was successfully applied in a phase 0/2 clinical trial to assess the central nervous system penetration of LY3214996 and abemaciclib.     

《医用有机化学》课程中进行德育渗透

教学与德育有机融会贯通,是当前教育领域的共识。医学本科生秉承"以德载医"的精神,肩负"治病救人"的重任,因此德育教育在整个医学教学中占有重要的地位。《医用有机化学》教材中含有丰富的德育内容,高校教师传授专业知识的同时,在教学过程中巧妙的穿插辩证唯物主义、爱国主义和社会责任感的思政教育,可以帮助学生们树立正确的世界观和人生观。文章以医用有机化学课程为例,主要从教师的自身道德素养、德育在教学过程中的具体实践和德育实施过程中需要注意的问题三方面进行阐述,充分将新时代新理念融入大纲、教案和课堂中,化"知识"为"智慧",变"文化"为"品格",充分发挥医用有机化学课程的德育功能。     

Impact of Dentin Substrate Modification with Chitosan-Hydroxyapatite Precursor Nanocomplexes on Sealer Penetration and Tensile Strength

IntroductionThe purpose of this study was to evaluate the effect of dentin conditioning with chitosan-hydroxyapatite precursor (C-HA) nanocomplexes on the depth of tricalcium silicate sealer penetration into dentinal tubules and ultimate tensile strength (UTS).Methodssurface charge and size distribution for C-HA nanocomplex formulation was evaluated followed by bioactivity assessment of standardized films of C-HA nanocomplexes (n = 15) incubated in simulated body fluid. Mineralization potential was assessed with X-ray diffraction and Fourier-transform infrared spectroscopy, whereas scanning electron microscopy was used for ultrastructural evaluation. Static water contact angles and UTS were measured on dentin discs (n = 2/group) and dentin beams (n = 10/group) treated with/without sodium hypochlorite/EDTA and C-HA nanocomplex conditioning. In phase 2, the depth of sealer penetration after C-HA nanocomplex conditioning was evaluated using fluorescent imaging (n = 12/group). The percent area penetration and mean/maximum penetration depth were calculated at 4- and 6-mm levels from the root apex. Data from contact angle measurements, mechanical testing, and penetration assessment parameters were subjected to the independent samples t test with a significance level set at P < .05.ResultsA formulation of C-HA nanocomplexes (2 mg/mL) was chosen as a polyanionic, hydrophilic, nonaggregating concentration having bioactivity potential established through the formation of phosphate/carbonate bonds and the crystalline nature of the formed minerals. A significantly lower contact angle and higher UTS were registered for the C-HA nanocomplex–conditioned group (P < .05). Statistically significant (P < .05) greater sealer penetration was recorded at the 4-mm level for all assessment parameters and percent area penetration at 6 mm for the C-HA nanocomplex group.ConclusionsC-HA nanocomplex conditioning enhances dentin surface wettability to facilitate greater tricalcium silicate sealer penetration and UTS of dentin.     

Pharmacokinetics and brain penetration study of chlorogenic acid in rats

1. The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid (CGA) after intranasal administration in Charles–Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path.

2. The CGA is administered intravenously (IV) and intranasally (IN) at the dose of 10?mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method.

3. The study observes that CGA is rapidly absorbed in plasma with t_max of 1?min similar to IV route after IN administration. The peak plasma concentration and AUC_0–24 are higher by 3.5 and 4.0 times respectively in IV administration, compared to IN delivery that represents the significant less systemic exposure of CGA in IN route.

4. However, the concentration of CGA in the brain is 4, 6.5, 5.3, 5.2 and 4.5 times higher at 30, 60, 120, 240 and 360?min, respectively in IN administration compared to IV administration. The exposure of CGA in the brain after IN administration (AUC_{brain, IN}) was significantly greater (4 times) as compared to the exposure of CGA in the brain (AUC_{brain, IV}) after IV administration reflecting significant brain uptake of CGA through nasal route. Therefore, IN delivery of CGA can be a promising approach for the treatment of stroke and neurodegenerative disorders.