Interaction of glucagon with artificial lipid bilayer membranes

The enhancement of fluorescence emission from the tryptophan residue of glucagon, the quenching of that emission with acrylamide and with 5-doxyl and 16-doxyl stearic acid, circular dichroism spectra, the release of 6-carboxytluorescein, and polarized infrared attenuated total reflection (IR-ATR) spectra were used to study the interaction of glucagon with intact lipid vesicles and flat bilayers. Dimyristoylphosphatidylcholine bound the peptide only below the main transition temperature, thus confirming earlier results of Epand et al. (1977). However, the peptide is also bound by vesicles of unsaturated lipids above their transition temperature, suggesting an influence of lipid area on the binding process. Circular dichroism showed that binding to such vesicles also increases the helix content of glucagon. The IR-ATR study and a comparison with dynorphin-A-(I-13)-tridecapeptide revealed profound differences in orientation of the two peptides. The dichroic ratios and the derived order parameters indicated an isotropic orientation of the helical segments of glucagon, but did not exclude a principal orientation of the molecules lying flat on the nienibrane surface. In contrast, the axis of the dynorphin helix is clearly oriented normal to the interface. The two peptides also differ in their rates of 6-carboxyfluorescein release, suggesting a deeper penetration of the primary amphiphilic helix of dynorphin A-(I-13) than of the secondary amphiphilic helix of glucagon.     

Mefenamic acid-induced bilateral transient myopia, secondary angle closure glaucoma and choroidal detachment

Drug-induced secondary angle closure is quite common and in the majority of cases simply stopping the medication leads to rapid reversal of the condition and resolution of glaucoma. We describe here a patient who presented with secondary angle closure glaucoma and myopia following mefenamic acid ingestion which was managed successfully by stopping the medication, symptomatic treatment and reassurance.     

对原发性骨质疏松诊断的一些看法

原发性骨质疏松的诊断首先要除外继发性骨质疏松。后者包括的范围很广，内容也很多，需要广博的内科学基础和辨证的逻辑思维才能予以正确鉴别。骨密度检查只能作为一种参考，而不能作为诊断原发性骨质疏松的唯一依据。     

Delivering syringe exchange services through “satellite exchangers”: the Sacramento Area Needle Exchange, USA

An important operational aspect of Syringe Exchange Programmes (SEPs) is the venue of service delivery. This report describes the programmatic features of the Sacramento Area Needle Exchange (SANE), an illegal SEP operating in California, USA. SANE utilises “satellite exchangers” to distribute the bulk of its syringes and HIV risk reduction supplies. Advantages of relying primarily on Designated Exchangers (DE) for delivery of SEP services are that it: (1) allows for coverage of a large geographical area; (2) keeps operational cost low; (3) provides syringes to clients who may not want to or cannot use fixed site programmes; (4) limits the possibility of detection of programme personnel and clients by law enforcement. Limitations are that: (1) it is not as conducive as fixed sites to providing a wide range of ancillary services; (2) it may not be optimal for drug users who do not want to be reliant on other people for access to syringes; (3) those who receive services from a satellite exchanger may not derive as much counselling and referral services as direct exchangers. The lack of legal status, political support and adequate funding threatens the programme’s existence.     

Does gastric adenocarcinoma develop after the treatment of gastric lymphoma?

Two adult patients with the diagnosis of gastric lymphoma who developed adenocarcinoma of the stomach 8 years after the treatment are presented. Both patients were treated by subtotal gastrectomy followed by irradiation of 4,000–4,500 cGy to the epigastric region and six courses of chemotherapy (vincristine, cyclophosphamide, prednisolone). In our review of the literature, 16 cases of gastric adenocarcinoma following the treatment of gastric lymphoma were found and listed with details. The factors influencing the development of this secondary carcinoma, mainly those treatment related are discussed. The possible role of both radiotherapy and chemotherapy in shortening the latent period for the development of stump carcinoma is emphasized. © 1993 Wiley-Liss, Inc.     

Tacrolimus metabolite cross-reactivity in different tacrolimus assays

Objectives: Tacrolimus (FK506) is an immunosuppressive drug with great clinical promise. There is a controversy regarding the role of tacrolimus metabolites in immunosuppression and toxicity, and immunoassays and immunophilin binding assays have not been adequately tested for metabolite cross-reactivity. Methods are limited to HPLC and HPLC-MS for quantifying the parent drug. Mixed lymphocyte culture assay (MLC) is the preferred functional bioassay for the measurement of parent drug and active metabolites but it is not practical for routine laboratory use. Due to differences in assay methods and reagent specificity, the concentration of tacrolimus in a given specimen may vary among different assay kit manufacturers. The objective of this study was to evaluate the degree of cross-reactivity or interference of the three first-generation tacrolimus metabolites [13-O-demethyl (M-I), 31-O-demethyl (M-II) and 15-O-demethyl (M-III)] among two different tacrolimus immunoassays (Immunoassay: PRO-Trac II FK506, Abbott IMx tacrolimus-II); and the radioreceptor assays (RRA) using minor immunophilins (14, 37, and 52 kDa immunophilins) and tacrolimus binding protein (FKBP12).

Methods: First-generation tacrolimus metabolites (M-I, M-II, and M-III) spiked in drug-free whole blood were assayed with RRA using three minor immunophilins (14, 37, and 52 kDa) and two commercial immunoassay procedures (Incstar PRO-Trac II tacrolimus, Abbott IMx tacrolimus II). The results were compared to previously published FKBP-12 RRA data and their immunosuppressive potency.

Results and conclusion: The first generation tacrolimus metabolites (M-I, M-II, and M-III) were tested using concentrations of 10 and 20 ng/mL. The significance of the metabolite interference (% of the total interference) was calculated based on the relative concentration of each metabolite present at steady-state trough concentrations in renal transplant recipients [22]. Metabolite I, which has no functional immunosuppressive activity showed minimal interference compared to M-II and M-III in all assays except the 14 kDa RRA. The Incstar PRO-Trac II tacrolimus assay showed the least M-I interference. Metabolite-II, which has a pharmacologic potency similar to the parent drug, showed a significant interference in the immunoassays and significant interference in radioreceptor assays. Metabolite III, which is pharmacologically inactive, produces 3–10% interference in the different assays if its presence in the blood is 6% of the parent drug. The total interference from these three metabolites was greater in the immunoassays than in the receptor assays. Receptor assays for tacrolimus provide results closer to the target value than do immunoassays.     

从脾论治磺脲类降糖药继发性失效

对 64例 2型糖尿病继发磺脲类降糖药失效患者 ,在继续口服磺脲类药的基础上加用健脾中药 ,结果显效 1 5例 ,有效 3 6例 ,无效 1 3例 ,总有效率 85 .2 4% ;治疗前后血糖明显下降 ,有显著性差异 ( P<0 .0 0 1 )     

玻璃体切除术治疗晶体脱位继发性青光眼

目的 :探讨玻璃体切除术治疗晶体脱位继发青光眼的疗效。方法 :晶体脱位继发青光眼 2 9眼 ,行前部玻璃体切除术联合晶体摘除 14眼 ;睫状体扁平部三孔闭合式玻璃体切除术联合晶体摘除 15眼。一期植入人工晶体 12眼。结果 :随访 2 2眼 1～ 12月 ,平均 8.5月。 18眼眼压 <2 1mmHg ,2眼局部滴抗青光眼眼水 ,眼压为 2 4mmHg ,2眼口服降眼压药物 ,眼压为 2 4 .0 0± 3.2 5mmHg。视力提高 16眼 ,无变化 6眼。结论 :玻璃体切除术治疗晶体脱位继发青光眼安全有效     

Cerebrospinal fluid purine metabolites after complex febrile convulsions

Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and uric acid were determined in cerebrospinal fluid (CSF) of 15 children after complex febrile seizures (CFS) and in 27 after simple febrile seizures (SFS), and compared with those in a control group of 63 children. There was no statistically significant difference between the groups for any of these metabolites, suggesting that CFS and SFS neither significantly disturb the metabolism of nucleotides, nucleosides or bases nor significantly deplete neuron adenosine triphosphate levels.