-Hydroperoxy diethyl peroxide, an unusual natural compound isolated from an ascidian (Phallusia mammillata): acute toxicity in DDY mice

-Hydroperoxy diethyl peroxide, a novel compound found in the tunic of ascidians, has two peroxide moieties per molecule. Since ascidians are a widely served food item in Japan, human exposure to this compound potentially exists in the seafood preparation industries. No toxicological data have so far been published on this compound, and so we determined the intraperitoneal 6-day LD₅₀ in mice and conducted histopathological examinations. The 6-day LD₅₀, was found to be 199 mg/kg with 95% confidence limits of 126–314 mg/kg. Histopathological examination revealed necrosis induced in a variety of cells that had been directly exposed to the compound. These cells included hepatocytes, parenchymal pancreatic cells and fat cells. It is concluded that direct contact with this compound is likely to elicit cellular necrosis of various organs. The specific toxicological effects are probably dependent on the route of exposure.     

Fine Mapping Functional Sites or Regions from Case-Control Data Using Haplotypes of Multiple Linked SNPs

Previously, we reported an algorithm for scanning a large number of tightly linked single nucleotide polymorphisms (SNPs) for LD mapping of functional sites or regions from a family‐based association design. In the present study, we extend our method to a case‐control design. We first use the expectation maximization (EM) algorithm to estimate haplotype frequencies of multiple linked SNPs, and follow this by constructing a contingency table statistic S for LD analysis, based on the estimated haplotype frequencies. An empirical p‐value is obtained based on the null distribution of the maximum of S (S *) from a large number (e.g., 1,000 or more) of randomized permutations. The proposed algorithm has been implemented in a computer program in which window searching for functional SNP sites can cover any number of loci without limitation, except that of computer storage. Unlike other programs for a case‐control design that always conduct tests at a fix window width, in our program after setting a maximum size of haplotype window width, for a given maximum window width all possible widths of haplotypes are utilized to find the maximum statistic S * for each locus under investigation. The sensitivity of the proposed algorithm has been examined with simulated and real genotyping datasets. Association analyses indicate that our program is powerful enough to detect most, if not all, functional SNPs simulated in the original model or identified in the original report. Moreover, the program is very flexible and can be used in either regional or genome‐wide scanning for association analysis with SNP markers.     

Control of the rat's circadian self-stimulation rhythm by light-dark cycles.

Rats with hypothalamic and septal electrodes were maintained in continuous test environments where bar-press responses produced brief reinforcing electrical stimulations. Long-term trends in response emission were measured under continuous exposure to light, dark and 12 hr light-dark alternations. In addition, transient behavioral adjustment to sudden 180 degrees phase shifts in the light-dark schedule was studied. The ambient light condition was found to control the period and phase of the circadian rhythm of brain self-stimulation behavior, as quantified by Fourier analysis. The circadian period was greatest under constant light (up to 24.90 hr under dim illumination), and approximated 24.00 hr under constant dark. Successful nocturnal entrainment to 12 hr light-dark alternations was obtained, with the peak of the 24 hr Fourier fundamental occurring in the middle-to-late dark segments. Three to 11 days were required for re-entrainment to 180 degrees light-dark phase shifts, during which the behavioral oscillation period increased to values comparable to periods under constant light. The rate of re-entrainment appeared to be proportional to illumination intensity during light segments.     

万克灵消毒剂的毒理试验

目的：研究万克灵的毒性作用。方法：经口、粘膜、皮肤试验。结果：小鼠经口毒性试验未显示毒性。该消毒剂对家兔皮肤无刺激性,对家兔眼结膜有轻度刺激反应,50%万克灵消毒剂（甘油稀释）则属无刺激性。对豚鼠皮肤致敏变态反应阴性,对小鼠骨髓细胞染色体无效突变作用。结论：经毒理试验显示万克灵消毒剂是一种应用于室内空气安全可靠的消毒剂。     

甲基叔丁基醚的急性毒性研究

为研究国产甲基叔丁基醚（ＭＴＢＥ）的毒性,比较与国外产品的异同,选用大、小鼠及家兔,采用经口、呼吸道及皮肤等染毒途径,同时对国产及进口ＭＴＢＥ的急性毒性进行研究,结果表明：国产及进口ＭＴＢＥ的小鼠经口ＬＤ５０分别为２９４５．２和２９４４．４ｍｇ／ｋｇ,大鼠均为３４３３．６ｍｇ／ｋｇ。小鼠经呼吸道ＬＣ５０分别为７２９８８．３和９９６３０ｍｇ／ｍ３,大鼠为８５３２０和１０３４１０ｍｇ／ｍ３。急性中毒表现均为先兴奋,然后出现粘膜刺激症状,运动失调,活动减少,麻醉,最后死亡。兔经皮染毒仅见脱脂现象,无致炎、致敏或中毒作用。但对兔眼睛有较强致炎作用。结论：国产或进口ＭＴＢＥ的动物经口或经呼吸道急性毒性基本相同,均属低毒物,经皮属微毒物,但对兔眼有明显刺激和致炎作用     

厚朴干皮"发汗"(加工)前后的毒性实验研究

目的比较厚朴干皮未发汗品、发汗品毒性的大小;方法采用小白鼠灌胃及腹腔注射LD50测定方法,观察厚朴未发汗品、发汗品水煎剂对小鼠的毒性;结果厚朴干皮未发汗品、发汗品60g/kg口服3天均安然无恙,腹腔注射LD50厚朴干皮未发汗品为24.21±4.5g/kg,发汗品为2.67±0.45g/kg;结论厚朴干皮未发汗品、发汗品口服毒性小,厚朴干皮未发汗品的毒性低于发汗品.厚朴干皮有无发汗(加工)的必要,值得商榷和进一步研究.     

八厘麻毒素的提取及其半数致死量研究

目的从干燥羊踯躅果实中提取八厘麻毒素并测定八厘麻毒素的半数致死量（LD50）。方法将羊踯躅果实粉碎后,经乙醇浸泡、加热回流、硅胶层析及重结晶获得八厘麻毒素。选取18～22g小鼠20只,予不同剂量八厘麻毒素灌胃给药,观察15min内小鼠死亡与存活状况,采用Dixon-Mood法计算LD50。结果 13kg羊踯躅果实共提取出3g八厘麻毒素,采用序贯法测得八厘麻毒素的LD50为7.609mg/kg。结论应设法减少或消除羊踯躅中有效成分八厘麻毒素的毒副作用,在临床应用中发挥其最佳降压效果。     

中药仙鹤复方提取物急性毒性试验及对小鼠移植性肿瘤H22的抗肿瘤作用研究

目的 研究中药仙鹤复方乙醇提取物的急性毒性,以及中药仙鹤复方乙醇提取物和水提取多糖对小鼠移植性肿瘤H22的抑瘤作用,进而对中药仙鹤复方进行抗肿瘤活性研究.方法 测定中药仙鹤复方乙醇提取物的LD50,建立荷实体型肝癌H22小鼠模型,观察中药仙鹤复方乙醇提取物和水提取多糖的抑瘤作用.结果 中药仙鹤复方乙醇提取物的LD50为26.95g·kg-1,95%可信区间为21.99～33.01g·kg-1;中药仙鹤复方乙醇提取物9.25g·kg-1·d-1剂量组与中药仙鹤复方水提取多糖8.05g·kg-1·d-1剂量组时小鼠移植性肿瘤H22均有明显的抑制作用,其抑瘤率分别为49.2%(P＜0.01)和33.7%(P＜0.01).结论 中药鹤复方乙醇提取物和水提取多糖对小鼠移植性肿瘤H22有抑制作用.     

依托咪酯对布比卡因致惊厥作用的影响

目的 观察依托咪酯(etomidate,Eto)对布比卡因(bupivacaine,Bup)致惊厥作用及半数有效量(ED50)、半数致死量(LD50)的影响.方法 皮下注射3种不同剂量的依托咪酯20min后,腹腔注射致惊厥作用的布比卡因,观察小鼠惊厥潜伏期、持续时间、未惊厥数和死亡数;并以序贯法测定预先给予依托咪酯20min后布比卡因的致惊厥ED50和LD50.结果 依托咪酯2、4mg/kg可延长布比卡因致小鼠惊厥的潜伏期(P＜0.01),缩短持续时间(P＜0.01),减少惊厥发生数和死亡数;增大布比卡因致惊厥的ED50(P＜0.05,P＜0.01),增大布比卡因的LD50(P＜0.01).结论 依托咪酯能够拮抗布比卡因的致惊厥作用,降低布比卡因的毒性.     

百草枯对小鼠的急性毒性试验

目的 观察百草枯(Paraquat,PQ)对小鼠的急性毒性,计算其半数致死量(LD50).方法 给小鼠灌服不同浓度的PQ溶液,通过观察小鼠的活动和毒性反应,记录小鼠的死亡数,用概率单位法计算LD50.结果 给药后不同时间内,小鼠出现自由活动减少,濒死时呼吸频率加快、张口呼吸、鼻翼扇动等中毒症状,死亡高峰在2 h内,死亡原因为多脏器损伤.♂小鼠LD50=106.99 mg·kg-1,95%可信限范围为97.01～118.03 mg·kg-1;♀小鼠LD50=86.40 mg·kg-1,95%可信限范围74.54～100.14 mg·kg-1.结论 PQ属于中等毒农药,♀小鼠更敏感.