An alkylpolyglucoside surfactant as a prospective pharmaceutical excipient for topical formulations: The influence of oil polarity on the colloidal structure and hydrocortisone in vitro/in vivo permeation

There is a growing need for research into new skin- and environment-friendly surfactants. This paper focuses on a natural surfactant of an alkylpolyglucoside type, which can form both thermotropic and lyotropic liquid-crystalline phases. The aim of this study was to relate some physicochemical properties (characterised by polarisation and transmission electron microscopy, thermal analysis and rheology) of the three formulations based on cetearyl glucoside and cetearyl alcohol, to the results of in vitro and in vivo bioavailability of hydrocortisone (HC). The three formulations contained oils of different polarity (medium chain triglycerides: MG, isopropyl myristate: IPM and light liquid paraffin: LP), respectively. In vitro permeation was followed through the artificial skin constructs (ASC), while the parameters measured in vivo were erythema index: EI (using instrumental human skin blanching assay), transepidermal water loss (TEWL) and stratum corneum hydration (SCH). The vehicles based on cetearyl glucoside and cetearyl alcohol showed a complex colloidal structure of lamellar liquid-crystalline and lamellar gel-crystalline type, depending on oil polarity. Rheological profile of the vehicle was directly related to the in vitro profile of the HC permeation. In vivo results suggested that the vehicle with MG retarded the HC permeation, whereas less polar IPM and non-polar LP enhanced it. It is suggested that the enhancement is achieved either by a direct interaction with lipid lamellae of the SC or indirectly by improving skin hydration.

There were no adverse effects during in vivo study, which indicates a good safety profile of this alkylpolyglucoside surfactant.     

国外用体内X射线荧光技术对人体骨铅含量研究的概况

通过介绍国外人体骨铅测量的历史背景、多种器官铅含量的对比以及体内X射线荧光技术(In vivoXRF)测定骨铅研究的近期发展状况,探讨人体骨铅含量体内X射线荧光非损伤性测定的重要意义。     

A simple model describes large individual differences in simultaneous colour contrast

We report experimental evidence for substantial individual differences in the susceptibility to simultaneous colour contrast. Interestingly, we found that not only the general amount of colour induction varies across observers, but also the general shape of the curves describing asymmetric matching data. A simple model based on von Kries adaptation and crispening describes the data rather well when we regard its free parameters as observer specific. We argue that the von Kries component reflects the action of a temporal adaptation mechanism, while the crispening component describes the action of the instantaneous, purely spatial mechanism most appropriately labeled simultaneous colour contrast. An interesting consequence of this view is that traditional ideas about the general characteristics of simultaneous contrast must be considered as misleading. According to Kirschmann’s 4th law, for instance, the simultaneous contrast effect should increase with increasing saturation of the surround, but crispening predicts the converse. Based on this reasoning, we offer a plausible explanation for the mixed evidence on the validity of Kirschmann’s 4th law. We also argue that simultaneous contrast, the crispening effect, Meyer’s effect and the gamut expansion effect are just different names for the same basic phenomenon.     

In vivo 13C saturation transfer effect of the lactate dehydrogenase reaction.

Lactate dehydrogenase (LDH, EC 1.1.1.27) catalyzes an exchange reaction between pyruvate and lactate. It is demonstrated here that this reaction is sufficiently fast to cause a significant magnetization (saturation) transfer effect when the 13C resonance of pyruvate is saturated by a continuous-wave (CW) RF pulse. Infusion of [2-(13)C]glucose was used to allow labeling of pyruvate C2 at 207.9 ppm to determine the pseudo first-order rate constant of the unidirectional lactate-->pyruvate flux in vivo. During systemic administration of GABAA receptor antagonist bicuculline, this pseudo first-order rate constant was determined to be 0.08+/-0.01 s-1 (mean+/-SD, N=4) in halothane-anesthetized adult rat brains. In 9L and C6 rat glioma models, the 13C saturation transfer effect of the LDH reaction was also detected in vivo. Our results demonstrate that the 13C magnetization transfer effect of the LDH reaction may be useful as a novel marker for utilizing noninvasive in vivo MRS to study many physiological and pathological conditions, such as cancer.     

类固醇类激素联合携带Fas基因重组腺病毒治疗瘢痕疙瘩的体内实验研究

目的应用成功制备的携带人Fas基因的两种重组腺病毒,联合类固醇激素进行瘢痕疙瘩的动物实验研究,判断携带人Fas基因的重组腺病毒与类固醇激素联合治疗瘢痕疙瘩的效果。方法构建瘢痕疙瘩裸鼠模型。使用Ad-Fas(B),Ad-Fas(T)两种构建成功的腺病毒注射及其它辅助治疗手段,实施针对植入裸鼠皮下的瘢痕疙瘩组织的体内治疗方案。通过大体观察,常规病理及电镜观察检测瘢痕疙瘩组织块的变化。结果①单纯使用腺病毒注射后的瘢痕疙瘩组织块体积仅轻度缩小。②前期注射Ad-Fas(B)或Ad-Fas(T)后,使用类固醇激素作为后续治疗因素,其瘢痕疙瘩组织块均明显缩小。③使用腺病毒治疗后,能有效地减少曲安缩松的使用,从而减轻类固醇类激素治疗的副作用。结论①裸鼠为免疫缺陷动物,所以该结果并不能否认病毒的直接治疗作用,在免疫性动物体内直接注射腺病毒的治疗效果尚无结论。②重组腺病毒Ad-Fas(B)及Ad-Fas(T)的瘢痕疙瘩基因治疗的动物实验为瘢痕疙瘩的治疗展示了一条全新的途径。     

额部扩张皮瓣的手术设计

目的 探讨额部扩张皮瓣的手术设计。方法 对121例额、颞部瘢痕、斑痣、血管瘤等皮肤病变切除后的患者采用额部扩张皮瓣进行修复，并比较滑行皮瓣、易位皮瓣及旋转皮瓣的手术效果。结果 115例患者取得良好的手术效果，修复后皮肤弹性良好、颜色较理想、瘢痕较细小；4例患者扩张皮瓣的远端有0．5～1．0cm的坏死，行Ⅱ期瘢痕切除缝合术；2例患者有单侧眉上提，半年后好转。结论 易位皮瓣术后瘢痕明显，尽量少用或不用；旋转皮瓣可以充分利用扩张后“过剩”的皮肤。是一种值得推广的额部皮瓣设计方法。对皮瓣的周密设计并了解不同皮瓣的优缺点。对手术效果及术后并发症的预防非常重要。     

Cholecystokinin Excites Neostriatal Neurons in Rats via CCKA or CCKB Receptors

The effect of iontophoretically applied cholecystokinin (CCK) on neurons of the neostriatum was studied in rats anaesthetized with urethane. The most frequently observed effect of the sulphated octapeptide (CCK-8S) on striatal neurons was excitation. Spontaneously active neurons responded more often to CCK-8S than quiescent cells. Silent, primarily non-responsive neurons could often be stimulated with CCK-8S using glutamate to induce an ongoing discharge. Thus, 45.8% of the 177 neurons studied changed their discharge rate by more than 30%. Certain CCK receptor antagonists could prevent the effect of CCK-8S, fully or at least partly, in the majority of CCK-responsive neurons. The data suggest that cholecystokinin modulates the firing of active neostriatal neurons via the CCKA or the CCKB receptor type. Furthermore, we compared neuronal responses to glutamate with those recorded during concomitant administration of CCK-8S in order to study the interaction of both transmitters, which may be colocalized in striatal afferents. CCK-8S mainly enhanced the excitatory effect of glutamate on striatal neurons, but in several neurons the response to glutamate was reduced. The CCKB receptor antagonist could prevent CCK-8S from increasing the glutamate-induced activation.     

卡马西平片体外溶出度与体内吸收相关性

目的：考察卡马西平（ＣＢＺ）片溶出度与体内吸收的相关性。方法：应用ＺＲＳ－４溶出度仪测定卡马西平片的溶出度。４名男性健康志愿性ｐｏ单剂量２００ｍｇＣＢＺ用ＴＤｘ分析仪测定血药浓度，并按照Ｗａｇｎｅｒ－Ｎｅｌｓｏｎ公式计算药物吸收分数。结果：体外溶出度与体内药物吸收分数的相关系数ｒ＝０．９２６１，体外溶出度与体内药物吸收分数的相关系数ｒ＝０．９９７７。结论：ＣＢＺ片体外溶出度与体内吸收有较好的相关性     

氟罗沙星的体内外试验相关性研究

本文研究了新型喹诺酮类药物氟罗沙星体外溶出与体内吸收之间的相关性。实验表明，本品口服吸收在血清中达峰时间较快，作用持久，消除半衰期为９．６０ｈｒ。在人工胃液中溶出速率较快，在血清达峰之前，体内吸收与体外溶出量之间呈现良好的相关性。     

Correlation between in vivo and in vitro toxic effects of foreign compounds

Studies in rats in vivo and in isolated hepatocytes from the same species and strain of animal in vitro with the hepatotoxicant hydrazine have shown that despite measuring the same parameters in each system, the effects do not always show a quantitative or qualitative correlation. For example depletion of glutathione and ATP occurred in both systems but required a much higher concentration of hydrazine in vitro. The effects on triglyceride levels, citrulline synthesis and taurine levels in vivo were not observed in vitro and the inhibition of urea synthesis and cytotoxicity in vitro were not observed in vivo.Inhibition of protein synthesis proved to be the marker which showed the best correlation, occurring at a similar hydrazine concentration in vitro and in vivo although not to the same extent.The situation with other toxicants is variable, in some cases correlation is good, in others modification of conditions in vitro are required.