Negative symptoms in schizophrenia: considerations for clinical trials

There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally.     

Prenatal nicotine exposure increased duration of nicotine-induced analgesia in adult rats

The effect of prenatal exposure to nicotine on nicotine-induced analgesia was studied in rats. The analgesic effect of a single dose of nicotine (1 mg/kg SC) was measured by the tail-flick technique, and two subsequent studies were carried out. In the first study, 7-month-old male rats, born to dams chronically treated with nicotine during pregnancy (NIC), exhibited prolonged nicotine-induced analgesia compared to matched controls. The second study was designed to explore whether rats prenatally exposed to nicotine (NIC rats) are born with an increased sensitivity to nicotine and whether there is any sex difference. The analgesic effect of nicotine was tested on control and NIC rats of both sexes once a month from 2 to 7 months of age. At an early age, male but not female NIC rats, exhibited shorter analgesic responses to nicotine than did the matched controls. With increasing age, however, the duration of nicotine analgesia began to be prolonged in NIC rats of both sexes. Significant differences between control and NIC rats were found at the age of 6 and 7 months, in both sexes. Thus, rats prenatally exposed to nicotine are not born with an increased sensitivity to the analgesic effect of a single dose of nicotine. This phenomenon develops later, during the course of life, independently of gender.     

Steroidal spirooxetanes. I. Synthesis and antiandrogenic properties of some 17-spirooxetanoandrostanes

Pharmaceutical Chemistry Journal -     

Phase II evaluation of merbarone in renal cell carcinoma

Summary The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m² IV continuous infusion days 1–5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1–15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.     

Endothelium-derived relaxing factor released by 5-HT: distinct from nitric oxide in basilar arteries of normotensive and hypertensive rats.

1. The role of the endothelium in cerebrovascular responses to 5-hydroxytryptamine (5-HT) was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) in vitro. 2. Cumulative addition of 5-HT caused concentration-dependent contractions in ring preparations of SHR basilar arteries; the contractile response was smaller in WKY basilar arteries. 3. Removal of the endothelium enhanced markedly the contractile responses to 5-HT in WKY arteries but had only a slight effect in SHR arteries. The responsiveness to 5-HT in WKY arteries after removal of endothelium was comparable to that in SHR arteries. 4. The endothelium-dependent relaxation induced by acetylcholine in WKY basilar arteries was almost abolished by treatment with 10 microM methylene blue or 10 microM NG-nitro-L-arginine (L-NOARG). However, the response to 5-HT was not affected by treatment with methylene blue, L-NOARG or indomethacin. 5. Application of 10-20 mM K+ or 3.2 mM tetraethylammonium (TEA) did not change significantly, or only increased slightly, the resting tension, but markedly enhanced the contractile response to 5-HT in WKY arteries with endothelium. In contrast, the submaximal response to 5-HT in SHR arteries with endothelium was significantly enhanced by 0.3 mM TEA. 6. In the presence of 1 mM TEA, the application of 10 microM L-NOARG further enhanced the responses of 5-HT in WKY arteries with endothelium. In SHR arteries with endothelium, 10 microM L-NOARG per se enhanced slightly but significantly the responses to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)     

复治矽肺结核化疗效果观察

我们自１９８０～１９８８年对７９例复治矽肺结核进行化疗。其中绝大多数为慢性纤维化空洞性病例，均经细菌学证实，并由尘肺诊断组认定为矽肺合并结核。本组病例分别以ＫＭ、ＩＮＨ、ＲＦＰ、ＰＺＡ，或ＳＭ、ＩＮＨ、ＲＦＰ、ＥＢ联合，分两阶段治疗１８个月，获痰菌阴转７９．２％，其中ＫＨＲＺ与ＳＨＲＥ组分别为９３．９％与６８．２％（Ｐ＜０．０５）。自疗程结束追踪２～８年，其细菌复阳率分别为６．４５％和１０．０％（Ｐ＞０．１）。并对影响其过去治疗失败的原因及对策进行了讨论。     

天然水中三卤甲烷前体活性结构的研究

通过实验证实，可用腐植酸（ＨＡ）代表天然水中三卤甲烷（ＴＨＭｓ）的前体。单一模拟化合物（含一个活性空位碳原子的间苯二酚，三个活性空位碳原子的间苯三酚，及甲基酮类化合物的丙酮酸钠）氯化后氯信形成的规律与氯化ＨＡ的不一致。而间苯二酚与丙酮酸钠的混合物（１：４Ｗ／Ｗ）能很好地反映出ＨＡ中活性结构的特性。为今后研究ＴＨＭｓ的形成提供了一个可资定量比较的ＴＨＭｓ前体。     

健康人血清叶酸和维生素B_(12)水平的测定

本文对14岁以下健康小儿171名,成人30名及初生儿脐带血30份进行了血清叶酸和维生素B_(12)含量测定,171名小儿于采血前均经补足叶酸和维生素B_(12)。结果:血清叶酸(nmol/L)的正常值低限,<4岁者为6.1,4～14岁为8.4,成人为5.0;血清维生素B_(12)(pmol/L)的正常值低限,<1岁为459,1岁～成人为107。     

Biological activity of fluorinated 3,4-dihydroisoquinolines

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 26, No. 1, pp. 44–45, January, 1992.