Is cholic acid responsible for embryo-toxicity of the post-receptive uterine environment?

HPLC analysis of the embryo-toxic fraction of human uterinefluid, collected between the 22nd and 25th days of the menstrualcycle, revealed the presence of cholic acid at high concentrations.It is suggested that cholic acid could be responsible for theembryo-toxicity of the uterine environment, which follows thereceptive period for implantation.     

Glucocorticoids potentiate kainic acid-induced seizures and wet dog shakes

Glucocorticoid effects on kainic acid-induced motor seizures and wet dog shakes in rats were investigated by adrenalectomy and dexamethasone treatment. One-day adrenalectomy attenuated kainic acid-induced wet dog shakes and seizure activity. These effects were restored by dexamethasone. Administration of dexamethasone to non-adrenalectomized rats potentiated kainic acid-induced wet dog shakes and severity of seizure activity. These results suggest that glucocorticoids may play an important role in modulating the severity of kainic acid-induced seizures and wet dog shakes.     

Pesticide assessment: Protecting public health on the home turf

Pesticide regulation is examined in the context of Health Canada’s Pest Management Regulatory Agency’s assessment of the chlorophenoxy herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) for turf. 2,4-D is the most common herbicide used to kill weeds in grass.The medical literature does not uniformly indicate harms from herbicides. However, the balance of epidemiological research suggests that 2,4-D can be persuasively linked to cancers, neurological impairment and reproductive problems. These may arise from 2,4-D itself, from breakdown products or dioxin contamination, or from a combination of chemicals.Regulators rely largely on toxicology, but experiments may not replicate exposures from 2,4-D application to lawns because environmental breakdown products (eg, 2,4-dichlorophenol) may not accumulate and selected herbicides are possibly less contaminated. Dioxins are bioaccumulative chemicals that may cause cancer, harm neurological development, impair reproduction, disrupt the endocrine system and alter immune function. No dioxin analyses were submitted to the Pest Management Regulatory Agency, and the principal contaminants of 2,4-D are not among the 17 congeners covered in pesticide regulation. Independent assessment of all dioxins is needed, in tissues and in the environment.The 2,4-D assessment does not approach standards for ethics, rigour or transparency in medical research. Canada needs a stronger regulator for pesticides. Potentially toxic chemicals should not be registered when more benign solutions exist, risks are not clearly quantifiable or potential risks outweigh benefits. Until landscaping pesticides are curtailed nationally, local bylaws and Quebec’s Pesticide Code are prudent measures to protect public health. Physicians have a role in public education regarding pesticides.     

Parvalbumin-immunoreactive neurons in the cerebral cortex of the lizardPodarcis hispanica

An antibody against the calcium binding protein parvalbumin selectively labels a set of neurons in the cerebral cortex of lizards. Golgi-like immunostained bipolar, multipolar and pyramid-like neurons appear mainly located in the inner plexiform layers. Parvalbumin-immunoreactive (PARV-IR) puncta are concentrated in the cell layer of the dorsal and dorsomedial cortices showing a basket-like distribution. The morphology and distribution of PARV-IR neurons and puncta overlap GABA-immunostaining in the cerebral cortex of lizards. Thus, it is likely that PARV-IR neurons are a subset of the cortical GABAergic neurons of lizards.     

Comparison of assays for determination of peptide content for lyophilized thymalfasin*

Abstract: Precise determination of the peptide content in drug substance samples depends highly upon the particular peptide compound and methodology used. Four independent methods were evaluated and compared to determine which would produce the best experimental precision for analysis of thymalfasin (thymosin α‐1). Four different methods were evaluated including elemental analysis (CHN), quantitative amino acid analysis (AAA), high‐performance liquid chromatography (HPLC), and Kjeldahl. This study demonstrates that the AAA method is highly variable in one laboratory while quite precise in another laboratory. Similarly, HPLC results depended on the laboratory conducting the study with more precise values obtained under cGMP. On the contrary, the CHN method yielded highly precise [i.e. <2% coefficient of variation (CV)] values. As precise knowledge of protein content is fundamental for the compounding of final pharmaceutical product of a specific potency, the CHN analysis is recommended for peptide content determination of the drug substance thymalfasin.     

超声引导下犬肝注射醋酸高渗氯化钠混合液对射频消融毁损体积的影响

目的探讨超声引导下活体犬肝注射不同剂量的醋酸高渗氯化钠液(acetic acid hypertonic saline solution,AHS)后行射频消融(RFA),观察犬肝一次性毁损体积的变化。方法使用LDRF-120S多极RFA系统联合AHS对活体犬肝行RFA。健康成年杂种犬30只,随机分为5组(n=6)。A组:注射2ml AHS后立即行RFA;B组:注射2ml AHS后延时5min行RFA;C组:注射4ml AHS后立即行RFA;D组:注射4ml AHS后延时5min行RFA;E组:注射6ml AHS后立即行RFA。结果5组间平均起始阻抗差异无统计学意义(P>0.05);5组间平均消融时间差异有统计学意义(F=83.831,P<0.001),LSD-t检验分析各组间两两比较差异有统计学意义(P<0.001),在观察范围内E组平均消融时间最长;5组间平均毁损直径差异有统计学意义(F=53.488,P<0.001),在观察范围内E组平均毁损直径最大,LSD-t检验分析除D与E组间差异无统计学意义(P>0.05)外,其余各组间两两比较差异有统计学意义(P<0.001);网状纤维染色显示凝固坏死区及其邻近的正常肝组织均可见血管内血栓形成;E组在AHS注射过程中出现不同程度的外溢;A、B、C及D组14d内无动物死亡,E组死亡4只。结论活体犬肝局部注射AHS4ml后延时5min行RFA即可达到较理想的毁损体积。     

MR频谱检测乳酸的脉冲序列优化研究

目的通过改变一系列脉冲序列参数，以利于乳酸的最佳检测与定量分析。方法制作含乳酸玻璃模型。改变一系列的MR脉冲序列参数，应用点解析频谱序列(point resolved spectroscopy，PRESS)和激励回波序列(stimulated echo acquisition，STEAM)获得乳酸模型的相应频谱。另外，对12例脑病变患者和2例健康志愿者进行磁共振频谱检查，测量出每个波峰的峰高，并绘出序列变化曲线图。结果STEAM各波峰的峰向与PRESS序列一致，但STEAM各峰高均低于同等条件的PRESS峰。随着TE时间的延长，用乳酸模型测出的乳酸峰的峰高一序列曲线图呈波浪状变化，正向双峰在TE=26、270ms时共振波幅达到最大绝对值，负向双峰在TE=135～160ms之间达到最大绝对值。脑病变患者和健康志愿者的扫描结果表明，乳酸峰在优化的序列高于非优化的序列。结论优化的脉冲序列更有利于乳酸的检测与定量分析。     

市售三厂家18种复方氨基酸注射液的质量评价

目的对市售3厂家(A、B和E)共9批18种复方氨基酸注射液进行质量比较。方法参考国内外同类产品质量标准,从澄明度、透光率、性状、pH值、不溶性微粒、抗氧剂量、细菌内毒素和含量等方面进行比较。结果外观均为无色澄明液体,430nm波长处透光率均大于99%,pH在5.42～6.61间;A、B、E3厂不溶性微粒≥10、≥25μm的粒子数分别为1.41、0.32,0.83、0.21和1.55、0.56个/ml;抗氧剂的量分别为<33、近330和>500mg/L;细菌内毒素检查与含量测定符合中国药典及国家标准要求。结论不同厂家的产品质量确实存在一定的差异。     

Intravenous fate of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes

The objective of this study was to assess the in vivo fate of poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA)-based polyplexes after intravenous administration into mice. Circulation kinetics and tissue distribution in terms of plasmid localization and transfection efficiency were assessed. To gain more insight into the observed biodistribution and gene expression profile, the interaction of pDMAEMA-based polyplexes with blood components (erythrocytes and albumin) was investigated in vitro. In the case of i.v. injection of positively charged polyplexes at a dose of 30 microg DNA most of the radioactivity was found in the lungs and the liver 60 min after injection. In the case of pDMAEMA/DNA polyplexes with a negative charge, uptake occurred mainly by the liver. Administration of positively charged complexes at a 30 microg DNA dose resulted in reporter gene expression primarily in the lungs. Injection of negatively charged complexes and naked plasmid did not result in luciferase expression in any of the organs examined. In vitro turbidity experiments showed the induction of a charge dependent aggregation process upon addition of albumin to the polyplexes pointing out to the involvement of aggregate formation in the dominant lung uptake of the positively charged polyplexes. Also, incubations of polyplexes after pre-incubation with a physiological concentration of albumin with washed erythrocytes confirmed that polyplexes induce the formation of extremely large structures. This paper underlines the need for the design of systems with reduced interaction with blood components to promote the delivery of DNA to target tissues outside the lungs.