Guinea pig maximisation test for skin sensitisation: the use of fewer test animals

Current European Community (Annex V) guidelines recommend the use of 20 test animals in the guinea pig maximisation test for skin sensitisation. The suitability, for classification and labelling purposes, of reducing the number of test animals has been examined by analysing the results of 40 studies submitted to the Health and Safety Executive, and by the use of a mathematical model. Our results suggest that in most cases an experiment with ten test animals can be used to determine satisfactorily whether a substance should be labelled with the risk phrase may cause sensitisation by skin contact. However, serious consideration should be given to the need for additional investigation if two or three of the ten test animals show a sensitisation response. The highest nonirritant concentration of a substance should be used at challenge. Clearer guidance in Annex V on evaluating challenge responses would be beneficial.     

Evidence for the existence of different receptor sites for algesic agents at the endings of muscular group IV afferent units

Summary The hypothesis that different receptor sites for algesic agents exist at free nerve endings in skeletal muscle has been tested by administering bradykinin and 5-hydroxytryptamine (5-HT) repeatedly in anaesthetized cats and evaluating the response behaviour of single group IV afferent units from the gastrocnemius-soleus muscle.Repeated intraarterial administration of bradykinin at intervals of 1 and 2 min usually elicited fibre responses without tachyphylaxis. Injections of equieffective doses of 5-HT, however, given in the same manner evoked fibre reactions that were strongly tachyphylactic. In units responding to both bradykinin and 5-HT a refractoriness to 5-HT could be induced by repeated injections of this agent without impairing the stimulating potency of bradykinin on the same nerve ending. Such a lack of cross-tachyphylaxis seems to apply also to the effects of histamine on one side and bradykinin or 5-HT on the other.These findings suggest that bradykinin, 5-HT and probably histamine exert their excitatory action on muscular group IV afferent units via different receptor sites.     

大豆低聚糖和低聚肽对高脂血症大鼠血管活性物质和血液流变学的影响

目的探讨大豆低聚糖(SOS)和大豆低聚肽(SOP)对高脂血症大鼠血管活性物质和血液流变学的影响。方法60只健康成年SD大鼠随机分为5组:分别饲喂正常饲料(正常对照组,NCG),高脂饲料(高血脂模型组,HCG),高脂饲料 2%SOS(SOS组)、高脂饲料 3%SOP(SOP组)、高脂饲料 2%SOS 3%SOP(SOSP组)8周,测定大鼠血脂、血管活性物质PG I2、TXA2、NO和血液流变学指标。结果各实验组均能显著降低高脂血症大鼠血清TC、TG、LDL-C,升高HDL-C,改善血脂水平。同时升高PG I2、NO,降低TXA2和TXA2/PG I2比值,还能降低血黏度和红细胞压积,并以复合干预组效果最佳。结论SOS和SOP具有良好的调节血脂、影响血管活性物质生成和改善血液流变学的作用,以联合使用效果最为显著。     

Proanthocyanidins and Flavan-3-ols in the Prevention and Treatment of Periodontitis—Immunomodulatory Effects,Animal and Clinical Studies

This paper continues the systematic review on proanthocyanidins and flavan-3-ols in the prevention and treatment of periodontal disease and covers the immunomodulatory effects, and animal- and clinical studies, while the other part discussed the direct antibacterial properties. Inflammation as a major response of the periodontal tissues attacked by pathogenic microbes can significantly exacerbate the condition. However, the bidirectional activity of phytochemicals that simultaneously inhibit bacterial proliferation and proinflammatory signaling can provide a substantial alleviation of both cause and symptoms. The modulatory effects on various aspects of inflammatory and overall immune response are covered, including confirmed and postulated mechanisms of action, structure activity relationships and molecular targets. Further, the clinical relevance of flavan-3-ols and available outcomes from clinical studies is analyzed and discussed. Among the numerous natural sources of flavan-3-ols and proanthocyanidins the most promising are, similarly to antibacterial properties, constituents of various foods, such as fruits of Vaccinium species, tea leaves, grape seeds, and tannin-rich medicinal herbs. Despite a vast amount of in vitro and cell-based evidence of immunomodulatory there are still only a few animal and clinical studies. Most of the reports, regardless of the used model, indicated the efficiency of these phytochemicals from cranberries and other Vaccinium species and tea extracts (green or black). Other sources such as grape seeds and traditional medicinal plants, were seldom. In conclusion, the potential of flavan-3-ols and their derivatives in prevention and alleviation of periodontal disease is remarkable but clinical evidence is urgently needed for issuing credible dietary recommendation and complementary treatments.     

京尼平苷对地鼠胆固醇结石形成的影响

目的观察京尼平苷预防给药对地鼠胆固醇结石形成的影响.方法用高脂肪高蛋白致石饲料造成地鼠胆固醇结石模型,阳性对照药物熊去氧胆酸80mg/kg和京尼平苷50,100mg/kgig,每天预防给药,给药30d后作胆囊内容物涂片检查观察地鼠的成石率,检测胆汁脂类成分计算胆汁成石指数.结果模型组的成石率为100%,成石指数(LI)大于1;京尼平苷50和100mg/kg组的成石率分别为40%(P＜0.05)和25%(P＜0.01),LI均小于1,熊去氧胆酸组的成石率与LI与京尼平苷100mg/kg组相近.结论京尼平苷对地鼠胆固醇结石的形成可能具有抑制作用.     

9种试点食药物质的安全性评价及试点风险监测现况

按照传统既是食品又是中药材的物质简称为食药物质,传统中医药常使用食药物质来防治疾病或养生保健。随着我国大健康产业的迅速发展,食药物质成为健康领域关注的热点。近年来,随着食药物质品种的增加,研发产品的创新种类和应用增多,拟新增食药物质的安全性问题成为关注重点。现综述国家卫生健康委员会和市场监督管理总局开展的按照传统既是食品又是中药材物质管理试点工作的9种试点食药物质的食用与药用价值、安全性和不良反应、国内部分省份风险监测内容和方案,以期为9种试点食药物质的食品安全风险监测工作的开展提供参考,为食药物质的合理应用和资源开发提供一定的依据。     

Effects of tri-iodothyronine (T3), insulin, insulin-like growth factor I (IGF-I) and transforming growth factor beta1 (TGFβ1) on the proportion of insulin cells in cultured embryonic chick pancreas

 With a view to ultimately identifying factors involved in the development of pancreatic insulin cells, we have cultured dorsal pancreatic buds from 5-day chick embryos on a basement membrane matrix (Matrigel) in a serum-free medium supplemented with selected factors. The endodermal components of the buds were freed of almost all the mesenchyme so as to eradicate as much as possible of this source of some such factors. In 7-day cultures, insulin and glucagon cells were demonstrated immunocytochemically; numbers of insulin cells were expressed as a percentage of insulin plus glucagon cell counts. Our standard medium contained insulin. Addition of tri-iodothyronine to this medium did not increase the proportion of insulin cells, but in combination with raised concentrations of glucose and essential amino acids it improved somewhat the marked increase previously recorded for these nutrient conditions. Omission of insulin from the standard medium greatly reduced the proportion of these cells; substitution of insulin by insulin-like growth factor I increased the proportion considerably more than did insulin. To test for an overall effect of growth factors, explants were cultured in standard medium on Matrigel containing reduced amounts of growth factors: the proportion of insulin cells proved to be increased over that reached on normal Matrigel. The suspicion that transforming growth factor β1, a component of Matrigel, might act to reduce the proportion of insulin cells was tested and found to be correct. It is suggested that the different factors studied here may affect either or both of proliferation and determination in the differentiation pathway of insulin vis-à-vis glucagon cells. Accepted: 13 March 1998     

Measurement of the vasoconstrictive substances endothelin,angiotensin II,and thromboxane B2 in cold storage solution can reveal previous renal ischemic insults

In a rat model, the left kidney was subjected to 60 min of normothermic ischemia followed by 15 min of reperfusion, whereas the right kidney, serving as a paired control, was not rendered ischemic. Both kidneys were then perfused in situ with either Euro-Collins (EC) solution (n=12) or University of Wisconsin (UW) solution (n=6) for 10 min. Each kidney was then harvested and stored at 4°C in its respective solution. After 24 and 48 h of cold storage, the following vasoactive substances were measured in the preservation media: endothelin (ET), angiotensin II (A-II), thromboxane (B₂) (TxB₂), and prostaglandin I₂ (PGI₂). After 24 h in EC solution, left kidneys uniformly produced significantly higher concentrations of each vasoactive substance than right kidneys: ET 1.64±0.3 pg/ml vs 0.82±0.1 pg/ml (P0.009); A-II 20.8±6.2 pg/ml vs 7.75+2.3 pg/ml (P0.007); TxB₂ 100.8±17.7 pg/ml vs 40.1±11.7 pg/ml (P0.04); PGI₂ 638.3±41.1 pg/ml vs 318.3±36.4 pg/ml (P0.001), respectively. At 48 h, a similar pattern of results was obtained as the kidney continued to produce TxB₂ and prostacyclins during the 24–48 h period. In the UW solution, basal levels of ET and A-II were lower than those in EC solution, but similarly increased after initial ischemia. At 24 h, the concentrations produced by the left and right kidneys were as follows: ET 0.66±0.1 pg/ml vs 0.48±0.1 pg/ml (P0.14); A-II 10.36±3.7 pg/ml vs 2.14±0.7 pg/ml (P0.006); TxB₂ 178±53 pg/ml vs 52±23.1 pg/ml (P0.001); and PGI₂ 448.3±49 pg/ml vs 323±44.3 pg/ml (P0.01), respectively. After 48 h, the range of concentrations of each substance was similar to that obtained after 24 h. In further studies, the concentrations of ET and A-II were measured in solution previously used to preserve human kidneys (n=7). The mean concentration of ET and A-II in these samples was 3.82±1.14 pg/ml and 21.3±9.2 pg/ml, respectively, whereas in control media both substances were below the limits of detection. These results demonstrate that vasoconstrictive substances can be measured in the preservation media after a kidney has been stored cold and that higher concentrations are found when the organ has been subjected to prior normothermic ischemia. The measurement of these vasoactive substances before transplantation may reveal that the kidney has been subjected to previous ischemic events. Moreover, these vasoactive substances could be involved in the early recovery of renal function after kidney transplantation.     

Modafinil, d-amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature

SUMMARY  Modafinil is an alerting substance that is considered safer than amphetamine with fewer side effects. Although modafinil has been used successfully to treat narcolepsy, relatively little is known about its ability to ameliorate fatigue and declines in mental performance due to sleep deprivation (SD) in a normal population. Forty-one military subjects received either 300 mg of modafinil, 20 mg of d-amphetamine, or placebo on 3 separate occasions during 64 hours of continuous cognitive work and sleep loss. Three drug treatments were given: at 23.30 hours and 05.30 hours during the first and second SD nights, respectively, and once at 15.30 hours during the third day of continuous work. Subjective estimates of mood, fatigue and sleepiness, as well as objective measures of reaction time, logical reasoning and short-term memory clearly showed better performance with both modafinil and amphetamine relative to placebo. Both modafinil and amphetamine maintained or increased body temperature compared to the natural circadian cycle observed in the placebo group. Also, from subject debriefs at the end of the study, modafinil elicited fewer side-effects than amphetamine, although more than the placebo group. Modafinil appears to be a good alternative to amphetamine for counteracting the debilitating mood and cognitive effects of sleep loss during sustained operations.     

铬结合物在铬中毒性肝损害中的作用

目的了解各种铬结合物与肝损害的关系。方法在铬中毒性肝损害的大鼠模型中,采用ＳｅｐｈａｄｅｘＧ５０凝胶层析技术,对肝中铬结合物进行分离和测定。结果铬染毒大鼠肝组织中,除可检出高分子铬结合物（ＨＭＷＣｒ,相对分子质量（ＭＷ）７００００～１２５００）及低分子铬结合物（ＬＭＷＣｒ,ＭＷ１２５００～５００）外,还发现对照组未检出的小分子铬结合物（ＭＭＷＣｒ,ＭＷ＜５００）。随染毒时间延长,肝损害加重,三者肝中分布变化明显：ＨＭＷＣｒ由２２．２％增至３７．０％;ＭＭＷＣｒ由２．２％增至５．０％;ＬＭＷＣｒ则从７５．６％降至５８．０％。结论ＬＭＷＣｒ可能与铬的解毒有关;ＭＭＷＣｒ的出现并增多反映了机体形成ＬＭＷＣｒ能力的紧张;ＭＭＷＣｒ可能是攻击靶器官的主要活性因素。