Interaction between thiol-modifying agents and P1075, a KATP channel opener, in rat isolated aorta

In vascular smooth muscle, openers of ATP-dependent potassium channels (K _ATP channels), such as P1075 (N-cyano-N’-(1,1-dimethylpropyl)-N’’-3-pyridylguanidine), produce relaxation. In this study we have investigated the effects of thiol-modifying agents on the binding of P1075 and on the ⁸⁶Rb⁺ efflux stimulating and vasorelaxant effects of the opener in rat aortic rings. The increase in ⁸⁶Rb⁺ efflux induced by P1075 was taken as a qualitative measure of K⁺ channel opening. The hydrophilic SH-group-oxidizing substance, thimerosal (1 to 100μM), abolished specific binding of [³H]-P1075 with an IC₅₀ value of 7.6±1.2μM; at 30μM, the half time for inhibition was 38min. Two other thiol-oxidizing agents, PMB (4-hydroxy-mercuribenzoic acid) and DTBNP (2,2’-dithio-bis(5-nitropyridine)), inhibited binding up to 86% and 44%, respectively. The disulphide bond reducing substance, DTT (1,4-dithiothreitol, 0.1 to 1mM), reduced [³H]-P1075 binding by up to 20% and partially reversed the inhibitory effect of thimerosal. In ⁸⁶Rb⁺ efflux experiments, thimerosal (3 to 100μM) concentration-dependently increased basal efflux but inhibited P1075-stimulated tracer efflux with an IC₅₀ value of 7±1μM. The inhibitory effect occurred with a half-time of approximately 8min and was essentially reversed by DTT. In rings precontracted with noradrenaline, thimerosal inhibited the vasorelaxant effect in a noncompetitive manner, shifting the concentration-relaxation curves to the right and reducing maximum relaxation.The data show that oxidation of thiol groups interferes with the binding of the K _ATP channel opener, P1075; concomitantly, the ⁸⁶Rb⁺ efflux stimulating and the vasorelaxant effects are inhibited. Reduction of disulphide bonds by DTT has only minor effects on the action of P1075. Collectively, the results suggest that intact thiol groups are essential for the functioning of the K_ATP channel in rat aorta. The different kinetics governing the inhibition of opener binding and of opener-stimulated ⁸⁶Rb⁺ efflux suggest that the SH-groups involved in the two processes differ in their accessibility to thimerosal and/or in their reactivity. Received: 7 April / Accepted: 9 July 1997     

带血管甲状腺-甲状旁腺移植术5例报告

用带血管的胎儿甲状旁腺移植术治疗甲状旁腺机能低下症,共行手术6次(腹腔内移植5次,股三角区移植1次),6次中有3例术后发生4次排斥反应。经1年8月至3.5年随防,疗效显著者2例,有效2例,失败1例。本文讨论了有关甲状旁腺移植的手术方法、注意事项、免疫抑制剂应用等问题。     

Evaluation of the safety of a non-animal stabilized hyaluronic acid (NASHA – Q-Medical, Sweden) in European countries: a retrospective study from 1997 to 2001

BACKGROUND: In Europe, several filler devices are currently on the market for use in aesthetic dermatology and some of them cause severe, permanent, adverse reactions. Since 1996 a non-animal stabilized hyaluronic acid (NASHA) from Q-Medical, Sweden, has been introduced and is becoming a leading product in aesthetic dermatology. Hyaluronic acid has no species specificity and skin testing is not recommended before treatment. OBJECTIVE: Our purpose was to evaluate the incidence of adverse reactions from 1997 to 2001 and the safety of NASHA after injections into the skin for aesthetic reasons. METHOD: Surveys were sent to physicians in European countries that agreed to participate. This is a retrospective study. A total of 12 344 syringes were sold by the Q-Medical to these physicians and we evaluated the total number of patients treated to 35% of this number (4320). We separated immediate hypersensitivity reactions from delayed reactions and analysed infectious and other types of reactions. RESULTS: From 1997 until 2001, 34 cases of hypersensitivity were reported: 16 cases of immediate hypersensitivity and 18 cases of delayed. The global risk of sensitivity is 0.8%. Since 2000, the amount of protein in the raw product has decreased and the incidence of hypersensitivity reactions is around 0.6%. As 50% of these reactions are immediate and resolved within less than 3 weeks, the risk of strong but transient, delayed reaction is around 0.3%. Four cases of abscess were reported. They were all sterile. No bacterial infection was found. Herpetic recurrence is possible after lip augmentation according to the technique of injection. No systemic reactions were reported. CONCLUSION: NASHA is a very useful and safe filler product. Skin testing does not seem to be necessary.     

两种工艺类肝素抗凝和降脂作用的比较

实验表明类肝素碱性处理者在抗凝与降脂上明显优于中性处理者;对小鼠的抗凝作用及TritonWR-1339诱发的大鼠高胆固醇血症的降胆固醇作用,二者在所试剂量范围内随剂量增加作用增强,但对TritonWR-1339性高甘油三酯血症,二者的作用强度未见此效应。     

Detection of proteinous toxins using the Bio-Threat Alert system, part 3: effects of heat pretreatment and interfering substances

We previously reported that the Guardian Bio-Threat Alert (BTA) system could detect (detection limit: about 0.1 μg/ml) staphylococcal enterotoxin B (SEB), botulinum toxins (BTX) A and B, and ricin, with no interference by white-powdered materials or colored matrices. In this study, the capability of the BTA system was further assessed. With 10 min of preheating at 60°C, all toxins could be detected, but with preheating at 80°C, BTX A and B and ricin became undetectable. About 20% SEB could be detected after heating at 80°C, but this detection ability was completely removed after heating at 100°C. The effects of chemicals usually used for decontamination, such as sodium hypochlorite, hydrogen peroxide, formaldehyde, and sodium nitrite, on the detectability of SEB, BTX A, or ricin in the BTA system were also tested. The concentrations giving 50% line intensity for SEB, BTX A, and ricin were 3.1, 11, and 15 μM for sodium hypochlorite and 88, 210, and 60 mM for formaldehyde, respectively. The addition of hydrogen peroxide or sodium nitrite did not decrease the detectability even when used at high concentrations.     

血脂康对急性冠状动脉综合征患者血清高敏C-反应蛋白、血脂蛋白的影响

目的观察急性冠状动脉综合征(ACS)患者血清高敏C-反应蛋白(Hs-CRP)、血脂水平变化及血脂康的干预情况。方法69例ACS患者随机分为血脂康组(40例)和常规治疗组(29例),治疗前后分别测定Hs-CRP、总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C);另30名健康人为对照组。结果与对照组比较,ACS患者Hs-CRP水平明显升高,且与心肌损害程度密切相关。血脂康治疗2周,能明显下调ACS患者的Hs-CRP水平。结论血清Hs-CRP水平与ACS的发生、严重程度密切相关,血脂康的抗炎作用在ACS的早期治疗中有重要意义。     

妊娠期妇女外阴阴道念珠菌病的病原学和治疗研究

目的 调查孕妇外阴阴道念珠菌病(vulvovaginal candidiasis，VVC)的发病率，对检出的VVC进行病原学和治疗研究。方法 连续对产科门诊1000例孕妇进行VVC发病情况调查。对分离的念珠菌进行体外抗真菌药物敏感试验。对66例VVC患者应用咪康唑栓治疗，400mg／d，6d为一疗程。结果 孕妇VVC的发病率为12．7％(127／1000)。37．4％(374／1000)的孕妇以往有VVC病史，0．6％的孕妇为复发性VVc。127例VVC中，白念珠菌、光滑念珠菌、热带念珠菌和克柔念珠菌分别占87．1％、9．9％、1．5％和1．5％。有4例患者同时感染2种念珠菌。114株白念珠菌对咪康唑、克霉唑、氟康唑、伊曲康唑、制霉菌素耐药率依次为10．5％、2．6％、6．1％、7．9％和0。13株光滑念珠菌对咪康唑和制霉菌素均敏感，对克霉唑、伊曲康唑和氟康唑均敏感或剂量依赖敏感。应用咪康唑栓治疗的患者在治疗完成后1～2周及4～6周的病原学治愈率分别为84．8％和80．3％。结论 VVC是孕妇的常见病，白念珠菌仍然是主要致病菌，其次为光滑念珠菌。常用抗真菌药物对引起VVC的念珠菌存在不同程度的耐药率，应用咪康唑栓治疗孕妇VVC效果满意。     

In vivo detection of single cells by MRI.

The use of high-relaxivity, intracellular contrast agents has enabled MRI monitoring of cell migration through and homing to various tissues, such as brain, spinal cord, heart, and muscle. Here it is shown that MRI can detect single cells in vivo, homing to tissue, following cell labeling and transplantation. Primary mouse hepatocytes were double-labeled with green fluorescent 1.63-microm iron oxide particles and red fluorescent endosomal labeling dye, and injected into the spleens of recipient mice. This is a common hepatocyte transplantation paradigm in rodents whereby hepatocytes migrate from the spleen to the liver as single cells. One month later the animals underwent in vivo MRI and punctuated, dark contrast regions were detected scattered through the livers. MRI of perfused, fixed samples and labeled hepatocyte phantoms in combination with histological evaluation confirmed the presence of dispersed single hepatocytes grafted into the livers. Appropriate controls were used to determine whether the observed contrast could have been due to dead cells or free particles, and the results confirmed that the contrast was due to disperse, single cells. Detecting single cells in vivo opens the door to a number of experiments, such as monitoring rare cellular events, assessing the kinetics of stem cell homing, and achieving early detection of metastases.     

消化性溃疡病因分析

[目的]探讨幽门螺旋杆菌感染和非甾体类消炎药应用与消化性溃疡的关系．[方法]对1062例消化不良患者进行内窥镜检壹、快速尿素酶实验和血清抗幽门螺旋杆菌免疫球蛋白检验，同时记录非甾体类消炎药的应用情况，计算消化不良患者消化性溃疡发病事、幽门螺旋杆菌感染率及非甾体类消炎药应用率．[结果]溃疡发病率为29．3％，幽门螺旋杆菌感染串为37．2％，非甾体类消炎药使用率为10．0％．[结论]幽门螺旋杆菌及非甾体类消炎药相互作用干上消化道黏膜．是引发消化性溃疡的重要病因．