抗生素89－07、庆大霉素和阿米卡星对豚鼠连续肌注15天的耳毒性初步比较

从功能与形态学两方面比较抗生素８９－０７、庆大霉素（ＧＭ）、阿米卡星（ＡＭＫ）对豚鼠耳蜗的影响，在豚鼠连续肌注１５天，停药１４天后，发现２００ｍｇ／（ｋｇ·ｄ）组庆大霉素与阿米卡星对耳蜗毛细胞平均损伤享为６３％与１０％，而相同剂量的抗生素８９－０７平均损伤率仅０．３％，说明抗生素８９－０７耳毒性极小，比ＧＭ和ＡＭＫ更为安全。     

抗生素89—07,庆大霉素和阿米卡星对豚鼠连续肌注15天的耳毒…

从功能与形态学两方面比较抗生素８９－０７，庆大霉素（ＧＭ），阿米卡星（ＡＭＫ）对豚鼠耳蜗的影响，在豚鼠连续肌注１５天，停药１４天后，发现２００ｍｇ／（ｋｇ．ｄ）组庆大霉素与阿米卡星对耳蜗毛细胞平均损伤率为６３％与１０％，而相同剂量的抗生素８９－０７平均损伤率仅０．３％说明抗生素８９－０７耳毒性极小，比ＧＭ和ＡＭＫ更为安全。     

抗生素89－07与奈替米星对豚鼠耳毒性的比较

９２只豚鼠分别肌注４种剂量的抗生素８９－０７、ＮＴＬ及生理盐水，２８ｄ后通过电生理、病理形态学检查，比较抗生素８９－０７与ＮＴＬ对豚鼠的耳毒性。结果显示：抗生素８９—０７与ＮＴＬ对听性脑干电反应阈值无显著影响。抗生素８９－０７较ＮＴＬ对前庭功能影响稍轻。耳蜗病变从扫描电镜、耳蜗铺片所见抗生素８９－０７较ＮＴＬ轻。内耳切片观察两药无显著区别．前庭病变各剂量总体相比抗生素８９－０７较ＮＴＬ轻。     

新型抗生素89—07对大鼠肾毒性的评价

抗生素８９－０７是庆大霉素新型的衍生物，给大鼠肌注３０、９０和１２０ｍｇ／ｋｇ，每日１次，为期７ｄ或２１ｄ，并与庆大霉素（ＧＭ）等剂量进行肾毒性比较，结果表明，ＧＭ１２０ｍｇ／ｋｇ组引起大鼠肾功能的损害包括尿蛋白、尿糖、尿酶的活性，一般毒性症状和体重增长受抑制比抗生素８９－０７等剂量严重。病理组织学检查证明，ＧＭ和抗生素８９－０７的９０和１２０ｍｇ／ｋｇ剂量主要是肾近曲小管上皮细胞损伤，抗生素８９－０７仅有轻度近曲小管上皮细胞退行性改变，而ＧＭ除细胞退行变性外，有部分细胞坏死，肾小管内有蛋白管型和细胞管型。     

抗生素89－07的耳毒性试验Ⅱ．抗生素89－07与庆大霉素、阿米卡星对耳蜗形态的影响

抗生素８９－０７的耳毒性试验Ⅱ．抗生素８９－０７与庆大霉素、阿米卡星对耳蜗形态的影响戴树宏，缪亦安，余蕴山，施宁华，汪玉芳（镇江医学院，镇江２１２００１）１２３只豚鼠分别肌肉注射等效剂量的抗生素８９－０７、庆大霉素和阿米卡星，阴性对照物为生理盐水，每...     

抗生素89－07的耳毒性试验Ⅱ．抗生素89－07与庆大霉素、阿米卡星对耳蜗形态影响的比较

为进一步观察比较抗生素８９－０７与庆大霉素（ＧＭ）、阿米卡星（ＡＭＫ）对耳蜗形态的影响，本试验用１２３只豚鼠，以等效剂量给药２８ｄ，停药１ｄ后处死，取颞骨观察耳蜗铺片及火棉胶连续切片，并用扫描电镜进行形态学观察，根据毛细胞坏死数与形态观察，阴性对照生理盐水与抗生素８９－０７无显著差异，而盐水与ＧＭ和ＡＭＫ有非常显著的差异。抗生素８９－０７本身与ＧＭ、ＡＭＫ也有极其显著的差异，ＧＭ、ＡＭＫ的量效关系显著，而抗生素８９－０７不存在明显的量效关系。可见抗生素８９－０７对耳蜗形态学无明显影响。而ＧＭ、ＡＭＫ对耳蜗的损伤明显     

大鼠肌注抗生素89－07、阿米卡星和庆大霉素肾毒作用的比较

抗生素８９－０７、庆大霉素、阿米卡星按每天５０、１００、１５０ｍｇ／ｋｇ，ｉｍ给予大鼠。分别于给药后５、１０、１５天处死动物，取样作肾功能和肾脏光镜形态学检查，比较评价了３种氨基糖苷类抗生素的肾脏毒性，ｉｍ庆大霉素１００ｍｇ／（ｋｇ·ｄ）以上剂量的动物，给药后７天就出现死亡，５０ｍｇ组随给药时间的延长，肾功能异常的指标逐渐增多，肾小管上皮细胞也由个别散在性的坏死发展到大片状和广泛性的严重坏死。抗生素８９－０７和阿米卡星５０ｍｇ组，仅见个别肾功能指标异常，肾小管上皮细胞仅见混浊肿胀等变性，即使是１００ｍｇ组的肾小管上皮细胞坏死的程度也没有庆大霉素５０ｍｇ组严重。上述结果表明，抗生素８９—０７的肾毒作用明显比庆大霉素轻。     

抗生素89—07与奈替米星对豚鼠耳毒性的比较

９２只豚鼠分别肌注４种剂量的抗生素８９－０７、ＮＴＬ及生理盐水、２８ｄ后通过电生理、病理形态学检查，比较抗生素８９－０７与ＮＴＬ对豚鼠的耳毒性。结果显示：抗生素８９－０７与ＮＴＬ对听性脑干电反应阈值无显著影响。抗生素８９－０７较ＮＴＬ对前庭功能影响稍轻。     

抗生素89－07多次给予大鼠的毒性

抗生素８９－０７按每天３０、１００和１８０ｍｇ／ｋｇｉｐ给予大鼠，连续９０天，共检测７项血液学指标，１０项生化指标及２０多种组织脏器，给药后头２周内，１８０ｍｇ组部分动物出现行走缓慢，有３只动物死于给药后１７～２１天。３０天测定时，１００和１８０ｍｇ组的肌酐和尿素氮含量升高。病理组织学检查仅见肾小管上皮细胞呈水泡样变和混浊肿胀及散在性的坏死，１８０ｍｇ组比１００ｍｇ组重。上述变化停药后均呈恢复趋势。本试验揭示抗生素８９－０７的主要毒性靶器官是肾脏，１００ｍｇ以上剂量是中毒和致死剂量，３０ｍｇ以下剂量属基本安全剂量。     

抗生素89—07的局部刺激性试验

用新西兰大白兔比较了抗生素８９－０７和阿米卡星（ＡＭＫ）肌肉注射的肌肉刺激性。１００ｍｇ受试药物（按碱基计算）溶于１．０ｍｌ生理盐水中，１次注入一侧股四头肌。给药２４和９６ｈ，根据肉眼观察和病理组织学检查结果，判断局部肌肉损伤程度。本试验结果证明，肌注抗生素８９－０７引起的肌肉损伤程度比ＡＭＫ轻。     

Theoretical π-π* absorption and circular dichroic spectra of cyclic dipeptides

The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate circular dichroic spectra of cyclo(Gly-Gly), cyclo (Ala-Gly), cyclo(Ala-Ala), cyclo(Pro-Gly), cyclo(Pro-Ala), cyclo(Pro-Val), cyclo (Pro-D-Val), and cyclo(Pro-Pro) in the amide π-π* absorption band near 190 nm. Assuming a standard backbone geometry, spectra which are in fair to good agreement wth experiment are obtained for these molecules. The spectra are predicted to be sensitive to conformations of Pro and Val side chains. The effects of dipeptide ring folding on calculated CD spectra are mostly consistent with those found by other workers, except that it is found that a planar ring conformation of cyclo (Ala-Ala) and cyclo (Ala-Gly) gives predicted spectra comparable to experiment. The same model gives theoretical absorption spectra consistent with available experimental data.     

Effects of Nitro-L-Arginine on Blood Pressure and Cardiac Index in Anesthetized Rats: A Pharmacokinetic-Pharmacodynamic Analysis

Purpose. Nitric oxide synthase (NOS) inhibitors such as Nitro-L-arginine (L-NA) are being considered for the management of hypotension observed in septic shock. However, little information is available regarding the pharmacokinetic and pharmacodynamic properties of these agents. Our objective was to examine the relationships between L-NA plasma concentration and various hemodynamic effects such as cardiac index (CI), mean arterial pressure (MAP), and heart rate (HR) elicited by L-NA administration in rats. Methods. L-NA was infused at doses between 2.5 – 20 mg/kg/hr in anesthetized rats over one hour. Hemodynamic effects and plasma L-NA levels were determined. Results. Infusion of L-NA resulted in dose-dependent increases in MAP and systemic vascular resistance (SVR), decreases in CI, and minimal change in HR. The relationships between the hemodynamic effects and plasma L-NA levels were not monotonic, and hysteresis was observed. Using nonparametric analysis, the equilibration half-time (t_1/2,keo) between plasma L-NA and the hypothetical effect site was determined to be 51.5 ± 6.6 min, 42.4 ± 10.1 min, 43.4 ± 9.0 min for MAP, CI, and SVR, respectively (n = 14). The E_max and EC₅₀ values obtained were + 32.5 ± 8.4 and 2.6 ± 1.3 g/ml for MAP and –52.9 ± 15.6 and 3.7 ± 1.8 g/ml for CI, respectively. Conclusions. Although L-NA can bring about beneficial elevation of MAP, such effect is always accompanied by a stronger effect on CI depression. Dose escalation of L-NA may bring about detrimental negative inotropic effect and loss of therapeutic efficacy.     

洛美沙星体内外抗菌活性研究

洛美沙星对革兰氏阴性菌具有强的抑菌活力。对克氏肺炎杆菌的抗菌活性最强,MIC_(50)为0.12mg/L;对痢疾杆菌、产气杆菌、粘质沙雷氏菌、不动杆菌和枸椽酸杆菌的MIC_(50)分别为1和4mg/L。洛美沙星对肠细菌科细菌的活力比诺氟沙星和依诺沙星强2～16倍,明显地比丁胺卡那霉素、庆大霉素强。对金葡球菌MIC_(50)为1mg/L, MRSA对洛美沙星同样敏感。洛美沙星对表葡球菌、链球菌、粪链球菌及肺炎双球菌等的抗菌活性与地氟沙星相似,比诺氟沙星、依诺沙星、丁胺卡那霉素、庆大霉素和头孢三嗪分别强2～4倍。 洛美沙星对小鼠全身感染的疗效优于诺氟沙星。对大肠杆菌、克氏肺炎杆菌和绿脓杆菌感染小鼠iv的ED_(50)分别是0.74、0.13和3.45mg/kg, po的ED_(50)分别是0.94、1.46和6.20mg/kg。     

乙酰吉他霉素临床前药理学研究

乙酰吉他霉素对临床分离的革兰氏阳性球菌有较好的抑菌活力，其对金葡球菌、β－溶血性链球菌、表葡球菌的ＭＩＣ_（５０）分别为１、０．２２和４ｍｇ／Ｌ，对耐红霉素、青霉素的金葡球菌、表葡球菌半数以上较敏感，与吉他霉素相似，但其对革兰氏阴性菌无明显作用。乙酰吉他霉素对小鼠实验性细菌感染有明显保护作用。对金葡球菌、肺炎双球菌感染小鼠口服用药的ＥＤ_（５０）分别为７９．６和２５．１ｍｇ／ｋｇ。其疗效与吉他霉素、麦白霉素、乙酰螺旋霉素相似。乙酰吉他霉素小鼠１次口服的ＬＤ_（５０）＞１５ｇ／ｋｇ，与吉他霉素相比毒性无差异。     

HPLC法测定丝裂霉素C聚氰基丙烯酸正丁酯纳米粒中丝裂霉素C的含量

目的:建立高效液相色谱法测定丝裂霉素 C 聚氰基丙烯酸正丁酯纳米粒(MMC-PBCA-NP)中药物含量。方法:采用C_(18)柱(4.6 mm×150 mm,5 μm),以混合磷酸盐缓冲液-乙腈(85:15)为流动相,流速为1 mL·min~(-1),紫外检测器,检测波长为365 nm。结果:丝裂霉素 C(MMC)浓度在5～250 μg·mL~(-1)范围内与峰面积呈良好的线性关系,r=0.9998;平均回收率(n=6)为98.15%。结论:本法专属性强,操作简便,结果准确。适用于 MMC-PBCA-NP 的质量控制。     

The pathogenesis of,and pharmacological treatment for,Canavan disease

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大鼠溃疡性结肠炎模型的实验研究

目的对不同剂量的三硝基苯磺酸（ＴＮＢＳ）引起的大鼠溃疡性结肠炎（ＵＣ）模型进行观察和评价。方法采用一次性直肠注入大鼠ＴＮＢＳ（２５～１５０ｍｇ·ｋｇ－１）的３０％乙醇溶液，引起慢性炎症性肠疾病（ＩＢＤ），３ｗｋ后外死动物对各剂量下动物结肠的重量、髓过氧化物酶（ＭＰＯ）活性及组织形态学变化进行观察和评价。结果ＴＮＢＳ在１００～１５０ｍｇ·ｋｇ－１剂量下引起的ＵＣ肠壁明显增厚，炎症和溃疡至少维持７ｗｋ时间，ＭＰＯ活性值显著性升高，组织学检查发现粘膜及粘膜下层有大量中性粒细胞及淋巴细胞、巨噬细胞、纤维细胞浸润，肉芽组织及隐窝脓肿形成，５０ｍｇ·ｋｇ－１剂量时有一较轻度的损伤。２５ｍｇ·ｋｇ－１时对结肠的重量、ＭＰＯ活性及损伤指数都没有显著性改变（Ｐ＞０．０５）。结论用ＴＮＢＳ引起大鼠实验性ＵＣ，其溃疡和炎症维持一较长时间，这一病理特征为炎症性疾病防治药物的研究提供了条件；本模型的最佳剂量为１００ｍｇ·ｋｇ－１左右     

Protective role of exogenous α-lipoic acid (ALA) on hippocampal antioxidant status and memory function in rat pups exposed to sodium arsenite during the early post-natal period

The present work focussed on the effect of exogenous α-lipoic acid (ALA) administration on retention memory and oxidative stress markers in the hippocampus subsequent to early post-natal exposure of rat pups to sodium arsenite (NaAsO₂). Wistar rat pups were divided into the control groups receiving either no treatment (Ia) or distilled water by intraperitoneal route (i.p.) (Ib) and the experimental groups receiving either NaAsO₂ alone (1.5 and 2.0?mg/kg body wt.) (IIa, IIb) or NaAsO₂ (1.5 and 2.0?mg/kg body wt.) followed by ALA (70?mg/kg body wt.) (IIIa, IIIb) (i.p.) from post-natal day (PND) 4–15. The initial and retention transfer latency (ITL and RTL) was determined on PND 14 and 15 using elevated plus maze. The animals were sacrificed by cervical decapitation (PND 16) and the brains were obtained. The dissected out hippocampus was processed for estimation of oxidative stress markers, glutathione (GSH), and superoxide dismutase (SOD). NaAsO₂ exposure resulted in longer RTL in animal groups IIa and IIb, thereby suggestive of arsenic-induced impairment in retention memory. RTL was significantly shorter in animal groups (IIIa, IIIb) receiving ALA following NaAsO₂, thereby suggestive of improvement in retention memory. GSH and SOD levels were significantly decreased in animals receiving NaAsO₂ alone as against group Ib and administration of ALA following NaAsO₂ increased the levels of hippocampal GSH and SOD. These observations are suggestive of the role of exogenous ALA in ameliorating the adverse effects induced by NaAsO₂ exposure of rat pups on retention memory and oxidative stress markers.     

Dinoflagellate polyether within the yessotoxin, pectenotoxin and okadaic acid toxin groups: Characterization, analysis and human health implications

Diarrhetic Shellfish Poisoning (DSP) is a specific type of food poisoning, characterized by severe gastrointestinal illness due to the ingestion of filter feeding bivalves contaminated with a specific suite of toxins. It is known that the problem is worldwide and three chemically different groups of toxins have been historically associated with DSP syndrome: okadaic acid (OA) and dinophysistoxins (DTXs), pectenotoxins (PTXs) and yessotoxins (YTXs). PTXs and YTXs have been considered as DSP toxins because they can be detected with the bioassays used for the toxins of the okadaic acid group, but diarrhegenic effects have only been proven for OA and DTXs. Whereas, some PTXs causes liver necrosis and YTXs damages cardiac muscle after intraperitoneal injection into mice. On the other hand, azaspiracids (AZAs) have never been included in the DSP group, but they cause diarrhoea in humans. This review summarizes the origin, characterization, structure, activity, mechanism of action, clinical symptoms, method for analysis, potential risk, regulation and perspectives of DSP and associated toxins produced by marine dinoflagellates.     

Latent role of in vitro Pb exposure in blocking Aβ clearance and triggering epigenetic modifications

Both β-amyloid (Aβ) catabolism and epigenetic regulation play critical roles in the onset of neurodegeneration. The latter also contribute to Pb neurotoxicity. The present study explored the role of epigenetic modifiers and Aβ degradation enzymes in Pb-induced latent effects on Aβ overproduction in vitro. Our results indicated that in SH-SY5Y cells exposed to Pb, the expression of NEP and IDE remained declined during the recovery period, accompanied with abnormal increase of Aβ_1-42 and amyloid oligomer. A disruption of selective global post-translational histone modifiers including the decrease of H3K9ac and H4K12ac and the induction of H3K9me2 and H3K27me2 dose dependently was also showed in recovery cells. Moreover, histone deacetylase inhibitor VPA could attenuate latent Aβ accumulation and HDAC activity induced by Pb, which might be by regulating the expression of NEP and IDE epigenetically. Overall, our results suggest sustained reduction of NEP and IDE expression in response to Pb sensitizes recovery SH-SY5Y cells to Aβ accumulation; however, administration of VPA is demonstrated to be beneficial in modulating Aβ clearance.