糖尿病视网膜病变的药物治疗进展

糖尿病视网膜病变是最常见的糖尿病微血管病变。目前有很多致力于延缓糖尿病视网膜病变的药物研究,包括对肾素-血管紧张素系统阻滞剂、蛋白激酶C抑制剂、血管内皮生长因子抑制剂、生长抑素类似物、抗炎药物、晚期糖基化终末产物抑制剂及醛糖还原酶抑制剂等的研究。本文就近几年在这些方面的研究工作作一综述。     

New antileukemic agents

Despite the tremendous progress in the treatment of childhood leukemias over the last 50 years, certain subgroups of children continue to have poor prognosis. Hence, there is a need for development of new antileukemic agents. In this review, the authors describe results of clinical trials of several new antileukemic compounds with different mechanisms of action (signal transduction inhibitors, nucleoside analogs, DNA hypomethylators, angiogenesis inhibitors, and monoclonal antibodies). Although most of these compounds are not used in pediatric leukemias, the concepts surrounding their clinical development are important to all pediatric hematologists/oncologists.     

β受体显像剂——碘（131）标记间碘苄胍标记方法的研究

本文采用亚铜作催化剂，研究了β受体显像剂－碘（１３ｌ）标记间碘苄胍的方法。１００℃水浴１０～１５分钟，标记率可达９９．９％。和经典的固相催化法相比，它不但快速、方便，而且不存在碘的损失和污染。该法可望将ＭＩＢＧ制成药盒以供临床大量使用。     

放射性碘标记RC-160对A549-hSSTR2细胞受体内化及杀伤作用的研究

目的研究^125I-伐普肽（RC-160）对转染人生长抑素2型受体（hSSTR2）基因的肺腺癌A549细胞（A549-hSSTR2）受体内化的规律，以及^125I-RC-160对A549-hSSTR2细胞的杀伤作用。方法采用放射性配基结合分析法，以^125I-RC·160为放射性配基，测定A549-hSSTR2细胞及未转染hSSTR2基因的A549（A549-pc3）细胞与^125I-RC-160在37℃温育不同时间（0．25，0．5，1，4，8，20和24h）的内化率；采用四甲基偶氮唑蓝（MTT）法测不同浓度^125I-RC-160、Na ^131I、RC-160对A549-hSSTR2细胞及A549-pc3细胞作用24，48，72和96h的杀伤作用。结果37℃条件下温育，^125I—RC-160迅速与A549-hSSTR2受体结合并使受体发生内化。在温育1h时，A549-hSSTR2细胞结合（膜结合＋内化）的放射性计数为总计数的（18．2±1．9）％，明显高于A549-pc3组[（5．7±1．4）％，P〈0．01]。1h后，A549-hSSTR2细胞膜受体内化率（内化部分放射性计数与总放射性计数比）随时间的延长继续增加，膜结合率（膜结合部分放射性与总放射性计数比）随时间的延长逐渐减少。至24h时，受体内化率达（13．0±1．1）％，膜结合率为（3．9±2．2）％。^125I-RC-160对A549-hSSTR2细胞的杀伤作用较对A549-pc3细胞明显增强，并呈一定的剂量-效应和时间-效应关系，在96h时，3700kBq／ml ^131I-RC-160对A549-hSSTR2的抑制率达（78．8±5．9）％。结论^125I-RC-160可以使转染hSSTR2基因的细胞膜受体内化；^131 I-RC-160对A549-hSSTR2细胞的杀伤作用较强，这为外源性受体基因介导核素靶向性内照射治疗肿瘤提供了实验依据。     

A review on the actual trends of insulin treatment in elderly with diabetes

The diabetes of the elderly subjects has two forms: diabetes of long duration, manifesting itself in younger or medium ages, and senile diabetes, appearing above the age of 65 years. The diabetes of the elderly has usually only modest symptoms: it is not ketosic, but in spite of this, in order to avoid the chronic-degenerative complications, it is important to maintain a good, even if not an optimal compensation. The therapeutic intervention cannot neglect a correct alimentary regime and a programmed physical activity in correlation with the clinical conditions of the patient. If the compensation is not achieved only with these tools, one can add oral antidiabetic treatments. In the elderly patients we usually observe primary or secondary failure of the oral antidiabetic treatments, and in such context we have to apply insulin treatment, even in cases of moderate glycometabolic decompensations. While we are waiting for the gene-therapy or the inhalatory insulin preparations, actually there are at disposal only the insulin analogs in rapid, slow and mixed forms. We propose two treatment schemes: (i) The first one consists of three administrations of rapid insulin with the meals, and on dose of slow insulin 2h after the last meal in the evening. (ii) The second scheme consists of one administration of rapid insulin at lunch, one administration of mixed insulin at dinner, with the addition of oral antidiabetics of peripheric action, in the morning and the evening. A better compliance can be obtained, being a fundamental aspect in the elderly diabetics, and a reduction of the number and severity of the hypoglycemia, which are the most important aspects in the elderly diabetes.     

Action of tubercidin and other adenosine analogs on Schistosoma mansoni schistosomules

The incorporation of the radiolabeled adenosine analogs tubercidin, formycin A, 9-deaza-adenosine, and adenine arabinoside into nucleotides of Schistosoma mansoni schistosomules was studied in vitro. Of the four analogs, only tubercidin and formycin A were incorporated into the nucleotide pool, at rates respectively one-tenth and one-fiftieth the rate of adenosine incorporation. Tubercidin inhibited schistosomule motility in vitro with an approximate IC50 value of 1 microM, whereas formycin A exerted no visible effect even when more of it than of tubercidin was incorporated into the nucleotides and nucleic acids. Formycin A thus acts like a nontoxic adenosine analog. 7-Deaza-adenine, the purine base of tubercidin, was not incorporated into nucleotides. 7-Deaza-adenine, 9-deaza-adenosine, and adenine arabinoside all had no effect on schistosomule motility at concentrations up to 100 microM. Formycin A blocked the incorporation of tubercidin and of adenosine with equal effectiveness, as did p-nitrobenzyl-6-mercaptopurine ribonucleoside, a specific inhibitor of nucleoside transport in many mammalian cells. Thus, formycin A, tubercidin, and adenosine appear to have a common mechanism of cellular uptake. The significant levels of adenosine phosphorylase and adenine phosphoribosyl transferase activity found in schistosomule extracts suggests that most of the transported adenosine is converted to adenine before conversion to AMP. The levels of adenosine kinase and tubercidin kinase, while low, can more than account for the rate of tubercidin incorporated into intact schistosomules. The kinase(s) may also represent a minor pathway for direct adenosine incorporation. It may have a rather unusual substrate specificity because it is able to recognize adenosine, tubercidin, and formycin A as substrates, but not 9-deaza-adenosine or adenine arabinoside.     

Probleme und Prinzipien der Hormontherapie des fortgeschrittenen Prostatakarzinoms

Summary The availability of hormones with few side effects has enlarged the indication for their use: In the presence of metastases, primary endocrine treatment which includes orchiectomy as standard therapy is employed with palliative intent. Adjuvant endocrine treatment is given after radical prostatectomy when positive margins or lymph nodes were present. A salvage endocrine treatment is administered if the primary tumor persists after radiotherapy or recurred after prostatectomy. The term diagnostic hormone treatment is misleading and should not be used. A secondary hormone application is supported by the observation that allaged hormone resistant tumor progressed after testosterone injection.The problem of early versus delayed endocrine therapy is unsolved, however, it is conceivable that the latter therapy is confronted with a larger tumor burden. The principle of endocrine treatment is properly described as means suppressing the androgenic stimuli. There are 5 different routes of androgen deprivation, among which the antiandrogens and LH RH analogs have the highest priority. Phase III — studies are under way to clarify their efficacy.

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Abkürzungsverzeichnis DES Diäthylstilboestrol - SHBG Sexual Hormon Bindungsgloblin     

Electronic and resonance effects on the lonization of structural analogues of efavirenz

The solubility of 4 analogues of efavirenz was studied as a function of pH. The study evaluated the ionization behavior and determined the relative contribution of electronegative substituents versus resonance effects on the pK_a value of the cyclic carbamate. The most profound lowering effect on the pK_a was due to the presence of multiple electronegative substituents and in particular the trifluoromethyl and acetylene groups. The presence of chlorine on the benzoxazinone ring was found to have a slight impact on the pK_a, although to a lesser extent. In the absence of any functional groups on the benzoxazinone ring system, the pK_a shifted to a value of 13.2, which is 3 pH units above that of efavirenz and more closely correlates with typical literature values for cyclic carbamates.     

2—氯—5—（5，6—二氢—2—甲基—1，4—氧硫杂环己二烯—3—甲酰胺基）苯甲酸异丙酯类似物的合成和生物活性

2－氯－5－（5,6－二氢－2－甲基－1,4－氧硫杂环己二烯－3－甲酰胺基）苯甲酸异丙酯（UC84）具有显著的抗病毒活性。合成了该化合物并以其为先导物模型制备了十一个结构未经报道的类似物,活性筛选试验表明该化合物有明显的抗乙肝病毒（HBV）和单纯疱疹病毒（HSV）活性。