Drug Absorption Through Mucosal Membranes: Effect of Mucosal Route and Penetrant Hydrophilicity

The influence of mucosal route and penetrant hydrophilicity on the in vivo absorption of a model lipophilic compound, progesterone, was investigated in ovariectomized rabbits. The absorption rate and systemic bioavailability of progesterone and its monohydroxy, dihydroxy, and trihydroxy derivatives were evaluated and compared following oral, nasal, rectal, and vaginal administrations. Nasal delivery resulted in a significantly higher rate and extent of progesterone absorption than oral, rectal, or vaginal administration. The rate and extent of mucosal absorption decreased as penetrant hydrophilicity increased for the nasal, rectal, and vaginal routes. The results of this investigation indicate that the absorption characteristics of a lipophilic compound, such as progesterone, are influenced by the properties of both the mucosa and the drug.     

人尿中苯丙哌林的比色测定法及其应用

本文利用苯丙哌林结构中活性亚甲基与显色剂(对-二甲氨基苯甲醛)酸性溶液呈粉红色专属性反应,建立了苯丙哌林尿液浓度的可见光比色测定法。其最低检测浓度为5μg/ml,平均回收率为100.9±4.0(%),相关系数r=0.9994,回归方程y=0.0107x-0.0339,日内误差CV(%)=2.60,日间误差CV(%)=4.23.6名健康志愿者口服苯丙哌林片剂100mg,尿药测定结果的1g△x/△t-t曲线出现前高型双峰现象,即服药后7h出现第一高峰,此时平均尿药排泄速度为1.90±0.15μg/h,30h出现第二高峰,此时其平均尿药排泄速度为1.61±0.09μg/h.     

结核菌素试验复强反应免疫机理的探讨

为探讨结核菌素试验复强反应免疫机理，我们在对河南省禹州市神地区常住人口３８９７人作了结核菌素（ＰＰＤ人型）皮试调查。试验分四组，即试验前组、皮试阴性组、皮试阳性组及复强反应组。随机抽样作外周血免疫学检测，结果显示：复强反应组与其他组相比，ＣＤ－３、ＣＤ－４阳性率均有所升高（Ｐ＜０．０５），但ＣＤ－４／ＣＤ－８比值无显著性差异（Ｐ＞０．０５）：血清免疫球蛋白及Ｃ－３测定，复强反应组ＩｇＭ高于皮试前及阴性组，但无统计学意义（Ｐ＞０．０５）；血清ＳＩＬ－２Ｒ检测，各组均比皮试前组升高，尤以复强反应组与皮试前组或阴性组比较为甚（Ｐ＜０．００１）；结核特异抗体测定复强反应组虽有升高，但与皮试前或阴性组相比差异不显著（Ｐ＜０．０５）；特异性结核循环免疫复合物测定，复强反应组与皮试前组及阴性组相比有显著性差异（Ｐ＜０．００１）。揭示复强反应的免疫机理很可能是ＰＰＤ刺激机体使Ｔ细胞免疫反应为主的特异性回忆应答。     

Characterization of invasive Neisseria meningitidis from Atlantic Canada, 2009 to 2013: With special reference to the nonpolysaccharide vaccine targets (PorA,factor H binding protein,Neisseria heparin-binding antigen and Neisseria adhesin A)

BACKGROUND:Serogroup B Neisseria meningitidis (MenB) has always been a major cause of invasive meningococcal disease (IMD) in Canada. With the successful implementation of a meningitis C conjugate vaccine, the majority of IMD in Canada is now caused by MenB.OBJECTIVE:To investigate IMD case isolates in Atlantic Canada from 2009 to 2013. Data were analyzed to determine the potential coverage of the newly licensed MenB vaccine.METHODS:Serogroup, serotype and serosubtype antigens were determined from IMD case isolates. Clonal analysis was performed using multilocus sequence typing. The protein-based vaccine antigen genes were sequenced and the predicted peptides were investigated.RESULTS:The majority of the IMD isolates were MenB (82.5%, 33 of 40) and, in particular, sequence type (ST)-154 B:4:P1.4 was responsible for 47.5% (19 of 40) of all IMD case isolates in Atlantic Canada. Isolates of this clone expressed the PorA antigen P1.4 and possessed the nhba genes encoding for Neisseria heparin-binding antigen peptide 2, which together matched exactly with two of the four components of the new four-component meningococcal B vaccine. Nineteen MenB isolates had two antigenic matches, another five MenB and one meningitis Y isolate had one antigenic match. This provided 75.8% (25 of 33) potential coverage for MenB, or a 62.5% (25 of 40) overall potential coverage for IMD.CONCLUSION:From 2009 to 2013, IMD in Atlantic Canada was mainly caused by MenB and, in particular, the B:4:P1.4 ST-154 clone, which accounted for 47.5% of all IMD case isolates. The new four-component meningococcal B vaccine appeared to offer adequate coverage against MenB in Atlantic Canada.     

Genetic and antigenic analysis of invasive serogroup C Neisseria meningitidis in Canada: A decrease in the electrophoretic type (ET)-15 clonal type and an increase in the proportion of isolates belonging to the ET-37 (but not ET-15) clonal type during the period from 2002 to 2009

BACKGROUND:

Serogroup C meningococcal disease has been endemic in Canada since the early 1990s, with periods of hyperendemic disease documented in the past two decades. The present study characterized invasive serogroup C meningococci in Canada during the period from 2002 to 2009.

METHODS:

Serogroup C meningococci were serotyped using monoclonal antibodies. Their clonal types were identified by either multilocus enzyme electrophoresis or multilocus sequence typing.

RESULTS:

The number of invasive serogroup C Neisseria meningitidis isolates received at the National Microbiology Laboratory (Winnipeg, Manitoba) for characterization has dropped from a high of 173 isolates in 2001 to just 17 in 2009, possibly related to the introduction of the serogroup C meningococcal conjugate vaccine. Before 2006, 80% to 95% of all invasive serogroup C meningococci belonged to the electrophoreic type (ET)-15 clonal type, and the ET-37 (but not ET-15) type only accounted for up to 5% of all isolates. However, beginning in 2006, the percentage of the ET-15 clonal type decreased while the ET-37 (but not ET-15) type increased from 27% in 2006 to 52% in 2009. The percentage of invasive serogroup C isolates not belonging to either ET-15 or ET-37 also increased. Most ET-15 isolates expressed the antigenic formula of C:2a:P1.7,1 or C:2a:P1.5. In contrast, the ET-37 (but not ET-15) isolates mostly expressed the antigens of C:2a:P1.5,2 or C:2a:P1.2.

CONCLUSION:

A shift in the antigenic and clonal type of invasive serogroup C meningococi was noted. This finding suggests vigilance in the surveillance of meningoccocal disease is warranted.     

血管紧张素Ⅱ诱导肾小球系膜细胞纤维连接蛋白产生的实验研究

目的：观察不同浓度的血管紧张素Ⅱ（ＡｎｇⅡ）刺激后系膜细胞ＡｎｇⅡ受体基因表达和分泌纤维连接蛋白（ＦＮ）的情况。方法：从６月龄人胎肾培养系膜细胞，经ＡｎｇⅡ刺激后用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）方法检测胎肾系膜细胞ＡＴ１和ＡＴ２受体ｍＲＮＡ的表达情况，分别用ＥＬＩＳＡ和ＲＴ－ＰＣＲ方法检测系膜细胞产生的ＦＮ和基因表达。结果：①经１０－８、１０－７、１０－６和１０－５ｍｏｌ／Ｌ的ＡｎｇⅡ刺激４８ｈ后，系膜细胞的ＡＴ１受体ｍＲＮＡ表达均有升高，并呈一定的浓度依赖性；而ＡＴ２受体ｍＲＮＡ仅在１０－５ｍｏｌ／Ｌ浓度的ＡｎｇⅡ刺激下才有微弱表达。②１０－７、１０－６和１０－５ｍｏｌ／Ｌ的ＡｎｇⅡ能明显促进系膜细胞产生ＦＮ和ＦＮ的ｍＲＮＡ表达的上调，并与ＡｎｇⅡ刺激浓度呈正相关。结论：ＡｎｇⅡ刺激后可使系膜细胞的ＡＴ１受体基因表达和ＦＮ的产生明显增加，并呈一定的浓度依赖性，而ＡｎｇⅡ高浓度可以使ＡＴ２受体表达上调