Hypersensitivity reactions to streptokinase in patients with high pre-treatment antistreptokinase antibody and neutralisation titres

After streptokinase or antistreplase administration, raisedantibody levels can persist for many years, but it is unclearif these antibodies can cause allergic reactions following streptokinasere-administration for myocardial re-infarction. Pre-treatmentantistreptokinase antibody (AB) and neutralisation litres (NT)were measured in 189 consecutive patients (57 received streptokinaseor anistreplase). Seven patients had previous exposure to streptokinaseor anistreplase; they had high mean (SEM) antibody litres of1:801 (332) and neutralisation litres of 3.3 (1.7) million units.The 182 patients without previous thrombolysis had mean (SD)antibody titres of 1:25 (3) and neutralisation litres of 0.14(0.08) million units; nine patients (4.95%), however, had raisedantibody litres of 1:160 and neutralisation litres of 0.3million units. Of the 15 patients with antibody litres of 1:160,three received streptokinase or anistreplase. Hypersensitivityreactions occurred in all three patients — neutralisationlitres 0.48, 1.5 and 1.1 million units respectively. Two becameseverely hypotensive with systolic pressures of 70 mmHg; onedeveloped a serum sickness-like reaction. Importantly, noneof the 54 patients with antibody titres of < 1:160 who receivedstreptokinase or antistreplase reacted adversely to the thrombolyticagents (² with Yates 's correction = 38.71 , P<0.01). Highantibody titres are associated with hypersensitivity reactionsto streptokinase. This has important implications in reinfarctionthrombolysis. In patients whose antistreptokinase antibody titresare likely to be raised the avoidance of streptokinase-relatedthrombolytic agents should be considered.     

Acute Toxicity of Helenalin in BDF1 Mice

Acute Tyyoxicity of Helenalin in BDF1 Mice. CHAPMAN, D. E.,ROBERTS, G. B., REYNOLDS, D. J., GRIPPO, A. A., HOLBROOK, D.J., HALL, I. H., CHANEY, S. G., CHANG, J., AND LEE, K. H. (1988).Fundam. Appl. Toxicol 10, 302-312. The acute toxicity of helenalin,a sesquiter-pene lactone isolated from Helenium microcephalum,was examined in male BDF1 mice. The 14-day LD50 for a singleip dose of helenalin in male mice was 43 mg/kg. A single ipinjection of 25 mg helenalin/kg increased serum alanine aminotransferase(ALT), lactate dehydrogenase (LDH), urea nitrogen (BUN), andsorbitol dehydrogenase within 6 hr of treatment. Multiple helenalinexposures, ip injection of 25 mg helenalin/kg for 3 days, increaseddifferential poly-morphonuclear leukocyte counts and decreasedlymphocyte counts. Serum ALT, BUN, and cholesterol levels werealso increased by multiple helenalin exposures at 25 mg helenalin/kg/day. Helenalin significantly reduced liver, thymus, and spleenrelative weights and histologic evaluation revealed substantialeffects of multiple helenalin exposures on lymphocytes of thethymus, spleen, and mesenteric lymph nodes. No helenalin-inducedhistologic changes were observed in the liver or kidney. Multiplehelenalin exposures (25 mg/kg/day) significantly inhibited hepaticmicrosomal enzyme activities (aminopyrine demethylase and anilinehydroxylase) and decreased microsomal cytochromes P-450 and65 contents. Three concurrent days of diethyl maleate (DEM)pretreatment (3.7 mmol DEM/kg, 0.5 hr before helenalin treatment)significantly increased the toxicity of helenalin exposure.The present studies indicate that the hepatic microsomal drugmetabolizing system and lymphoid organs are particularly vulnerableto the effects of helenalin. In addition, helenalin toxicityis increased by DEM pretreatments which have been shown to decreaseglutathione concentrations.     

ACUTE AND SUBCHRONIC NEUROMUSCULAR BLOCKING CHARACTERISTICS OF STREPTOMYCIN: A COMPARISON WITH NEOMYCIN

The characteristics of the neuromuscular block produced by streptomycinin vivo were studied on the sciatic-tibialis anterior nerve-musclepreparation of eight anaesthetized cats. The lungs of the animalswere ventilated mechanically and normocarbia was maintained.During acute exposure to streptomycin (within 2 h), ED₅₀ forblockade of the twitch was 56 (SEM ± 5) mg kg^–1of the base. The characteristics of block were similar to thoseof neomycin-induced block in some aspects. There was absenceof train-of-four fade and tetanic fade, partial sparing of theresponses elicited at 10 Hz and 20 Hz, and total sparing ofthe 50 Hz tetanus, as well as the post-tetanic twitch. In contrastto neomycin-induced neuromuscular block, however, post-tetanicexhaustion was not observed and prolonged exposure to streptomycin(22–28 h) did not change the characteristics of the block.We conclude that, despite their chemical similarities, streptomycinand neomycin block neuromuscular transmission differently. ^*An abstract was presented at the 1978 Annual Meeting of theAmerican Society of Anesthesiologists, October 1978, under thetitle "Antibiotic-induced neuromuscular block: phenomenologicaldifferences between streptomycin and another aminoglycosideneomycin".     

含氟牙膏对离体脱矿恒牙再矿化作用的实验研究

目的评价含氟牙膏促进离体脱矿恒牙再矿化的作用。方法选取和制作牙体硬度170KHN左右的16颗离体年轻脱矿恒牙标本,随机分成A、B两组(P>0.05)。A组用无氟Crest牙膏作再矿化处理,B组用含氟的Crest牙膏作再矿化处理,同时将A、B组标本浸泡于人唾液中。用微硬度测量仪测定并记录每个牙标本的硬度。结果A组脱矿牙的硬度平均值为151.9±38.3,而再矿化后牙齿的硬度平均值为143.4±18.8,两组比较P>0.05。B组脱矿牙的硬度平均值为160.1±16.5,而再矿化后牙齿的硬度平均值为200.5±21.3,两组比较P<0.05。再矿化后AB两组的硬度值比较P<0.001。结论含氟牙膏对离体脱矿恒牙有较明显的再矿化作用。     

Localized Intradermal Microinjection of Tranexamic Acid for Treatment of Melasma in Asian Patients: A Preliminary Clinical Trial

BACKGROUND: Melasma is a common cosmetic problem among Asians. While various treatments are currently being used, there is no entirely satisfactory treatment. It was recently reported that the topical plasmin inhibitor is an effective treatment for ultraviolet-induced hyperpigmentation. OBJECTIVE: Because there are no studies assessing the efficacy and safety of localized microinjection of tranexamic acid (TA) for the treatment of melasma, we conducted a pilot study to evaluate the efficacy and side effects of this potentially new method for the treatment of melasma in Korean women. METHODS: A total of 100 women with melasma, after written consent, were enrolled for a prospective open pilot study of 12 weeks. After applying topical anesthesia, 0.05 mL TA (4 mg/mL) was injected intradermally into the melasma lesion at 1 cm intervals by using a 0.5 mL insulin syringe with a 30-gauge needle. This was repeated weekly for 12 weeks. A clinical investigator evaluated the results by using the Melasma Area and Severity Index (MASI) at baseline and at 4, 8, and 12 weeks. The patient satisfaction questionnaire was documented at 12 weeks. Safety evaluations were performed at each follow-up visit. RESULTS: Eighty-five patients completed the trial. A significant decrease in the MASI from baseline to 8 and 12 weeks was observed (13.22+/-3.02 vs 9.02+/-2.62 at week 8 and vs. 7.57+/-2.54 at week 12; p<.05 for both). The patients' self-assessment of melasma improvement was as follows: 8 of 85 patients (9.4%) rated as good (51-75% lightening), 65 patients (76.5%) as fair (26-50% lightening), and 12 patients (14.1%) as poor (0-25% lightening). Side effects were minimal and all the patients tolerated the treatment well. CONCLUSION: Based on these results, we suggest that the intralesional localized microinjection of TA acid can be used as a potentially new, effective, and safe therapeutic modality for the treatment of melasma.     

兔耳动脉的交感性血管收缩对α肾上腺素能受体拮抗剂的部分阻抗(英文)

本文利用离体组织灌流技术,对刺激家兔颈上神经节内壁交感神经引起兔耳中央动脉收缩的本质进行探讨,α受体拮抗剂仅部分阻断跨壁神经刺激(TNS)引起的收缩,若预先使用利血平耗竭离体血管内源性儿茶酚胺,由TNS引起的此种家兔耳中央动脉收缩则明显减弱,与此同时,α受体拮抗剂却增强了后期(residual)收缩反应,这种增强作用可能是因突触前膜α受体同时被阻断而引起,由此可见,交感神经冲动引起的家兔耳中央动脉收缩绝大部分是由去甲肾上腺素(NE)介导的,但后期收缩反应则可能是由另一种不明递质所介导,而这种属于外周循环系统的耳动脉交感神经与血管之间冲动传递方式又有别于大脑动脉的传递方式。     

Survey of conformational role of ester bonds in a cyclic depsipeptide

The effect of ester bond on the conformation of peptide molecule was studied by designing and synthesizing a model tetradepsipeptide cyclo(-l -Ala-l -Hmb-)z and by analyzing the conformation both theoretically and experimentally. Theoretical analysis showed that both ester and peptide bonds in the calculated low-energy conformations within 3 kcal/mol of the global minimum take a trans but distorted configuration. The distortion is larger in ester bonds than in peptide bonds. Further, the four carbonyls project from one side of the plane of the cyclic backbone, whereas the side chains project from the other side. These results are consistent with the experimental results obtained by NMR measurement; first, the coupling constant deduced from ¹H-NMR species in DMSO-d₆ is consistent with the dihedral angles of the calculated low-energy conformations; second, results of NOE measurement can reproduce the calculated configuration of the carbonyls and side chains. From the consistency between theoretical and experimental results, it is concluded that this model tetradepsipeptide takes an all-trans backbone conformation in solution and this backbone conformation is stabilized by large distortion in the ester bond, which compensates the strain resulted from the 12-membered cyclic backbone structure consisting only of L-residues.