中间体氨化物的纯度及其对氨氯吡咪原料药质量的影响

应用高效液相色谱考察了用于制备氨氯吡咪的中间体３，５－二氨基－６－氯－２－甲氧基－羰基吡嗪（氨化物）的纯度。色谱含量分析与熔点测定结果相互支持，氨化物含量高的粗品有高的熔点。用较高纯度的氨化物制备的氨氯吡咪的质量较高。     

组织胺诱导胸腺细胞凋亡的研究

用苔盼蓝及吖啶橙染色，ＤＮＡ片段检定与ＤＮＡ电泳等方法进行组织胺诱导胸腺细胞凋亡的研究，旨在探讨其可能机制及其在胸腺细胞负选择中的作用。结果表明，组织胺诱导使体外培养的胸腺细胞出现典型的细胞调亡。雷尼替丁可阻断上述作用，提示胸腺细胞存在Ｈ＿２受体，活化该受体可能在胸腺细胞的负选择中起重要作用。     

Epidemiology of abdominal symptoms in a random population: Prevalence,incidence, and natural history

The study presents results from a five-year follow-up on abdominal symptoms in an age and sex stratified random sample of 4,581 Danes. Abdominal pain occurred significantly more often among women (prevalence: 49%, incidence: 21%) compared to men (prevalence: 38%, incidence: 15%). Five years later the pain had disappeared in 43% of the men and 31% of the women (p=0.003). Distension, borborygmi, and altering consistency of stools occurred with a prevalence of approximately 50% and an incidence of approximately 30%, significantly more often among women compared to men. Five years later these symptoms had disappeared in about 20%. Prevalence of both heartburn and acid regurgitation were significantly higher among men (38%) than women (30%), whereas no sex difference was observed regarding incidence of these symptoms (16%). Approximately 30% of subjects who had experienced heartburn or acid regurgitation did not do so five years later. In conclusion, abdominal symptoms occur frequently and recurrently in the general population. This information is of importance to doctors when they evaluate patients with abdominal complaints, but no obvious organic etiology.     

Altered enzyme activities of xenobiotic biotransformation in kidneys after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) to rats

Activities of the xenobiotic metabolizing enzymes were measured in the liver, kidney, duodenum and lung microsomes and cytosol fractions of Wistar rats after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a potent bacterial mutagen in chlorinated drinking water. MX was administered by gavage at the dose level of 30 mg/kg for 18 weeks (low dose), or at the dose level which was raised gradually from 45 mg/kg for 7 weeks via 60 mg/kg for 2 weeks to a clearly toxic dose of 75 mg/kg for 5 weeks (high dose). Microsomal and cytosolic preparations were made and the activities of 7-ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-dealkylase (PROD), NADPH-cytochrome-c-reductase, UDP-glucuronosyltransferase (UDPGT) and glutathione-S-transferase (GST) were measured. Kidneys were affected most. A dose-dependent decrease was observed in EROD (90% in males, 80% in females at the high dose) and in PROD (58% in females, at the high dose) in kidneys. An increase was, however, detected in kidney NADPH-cytochrome-c-reductase (66% in females at high dose), UDPGT (89% in males and 97% in females at high dose) and GST activities (56% in males and 50% in females at high dose). MX caused only a few changes in the enzyme activities of the liver. The EROD activity was decreased 25% to 37%, both in the livers of males and females, but the total content of P450s was not altered. Hepatic GST activity was elevated in females in a dose-dependent manner (31% and 44%). GST activity was elevated in duodenum in females (59%) at the high dose. There were no marked changes in the enzyme activities in the lungs. MX was a weak inhibitor of EROD activity both in the liver and kidney microsomes in vitro, decreasing the EROD activity by 53% and 43%, respectively at the concentration of 0.9 mM. The results indicate that MX decreases the activity of phase I metabolism enzymes, but induces phase II conjugation enzyme activities, particularly in kidneys in vivo. It is possible that these changes contribute to metabolism of MX in kidneys and renders them susceptible to MX in the course of repeated exposure.     

用Fura-2测定周围血单个核细胞内游离钙浓度

本文用Fura-2测定了周围血单个核细胞内游离钙浓度，并对有关实验条件进行了探讨。对比研究表明，血标本在4℃保存4小时对测定结果无显著影响，测定标本中单个核细胞数以10~5～10~6/ml为宜。认为测定单个核细胞内游离钙浓度对判断单个核细胞的功能状况有一定帮助。     

Short-term niflumic-acid-induced acute renal failure in children

Several reports emphasize the adverse effects of non-steroidalanti-inflammatory drugs (NSAIDs) on renal function. We haveobserved over the last 10 years seven cases of acute renal failure(ARF) due to immune interstitial nephritis in children. A recommendedoral or rectal dose of niflumic acid was prescribed for ear-nose-throatdisorders, Length of exposure was 1–5 days. Clinical symptoms (oedema, oliguria or anuria) appeared between3 and 6 days. Three patients had previously received the drug.Hypersensitivity signs (fever, skin rash, eosinophilia, and/orincreased IgE) were present in all cases, leukocyturia in fivecases, and haematuria in six cases. Renal biopsy showed interstitiallesions with lymphocyte, eosinophil, and plasma cell infiltrateswithout tubular cell necrosis. Glomeruli were normal on light-microscopy,except in one patient. Electron-microscopy showed extensivepodocyte fusion in two patients, who had clinical and laboratoryevidence of nephrotic syndrome (NS). ARF rapidly disappeared after NSAID withdrawal, except in twopatients whose renal failure was irreversible despite methylprednisolonebolus. ARF is very rare in children treated with niflumic acid.When ARF occurs, different pathophysiological mechanisms areinvolved but the most common is immunological.     

Inhibitory effects of chlorpheniramine and astemizolum on contraction of isolated rat and rabbit uteri induced by oxytocin and PGF2α

Summary The contraction of isolated rat and rabbit uteri induced by oxytocin and PGF_2α was markedly inhibited by chlorpheniramine (Chl) and astemizolum (Ast), both of which also decreased the resting tension of uteri, and their spontaneous contraction. The inhibitory effects of both drugs were dose-dependent. At high concentrations, Chl 7.4× 10^-4 mol/L and Ast 10^-4 mol/L could counteract the contraction of the uteri induced by Oxy and PGF_2α, and their spontaneous contraction as well. They decreased the resting tension to the lower level. The mechanism of their non-special relaxed action on uteri could not be completely explained only by their H₁-receptor blocking action. Whether they act by blocking calcium channel or by inhibiting calmodulin (CaM) remains to be further explored.     

C-erbB-2、MMP2在乳腺癌中的表达及相互关系探讨

目的 :探讨癌蛋白 (C erbB 2 )和基质金属蛋白酶 (MMP2 )在乳腺浸润性导管癌中的表达及相互关系。方法 :应用免疫组织化学S -P法对 5 6例乳腺浸润性导管癌的C erbB 2和MMP2的阳性表达进行检测分析。结果 :5 6例中有 37例 (6 6 % )C erbB 2过表达 ,39例 (6 9.6 % )MMP2过表达 ,C erbB 2和MMP2同时阳性表达者 32例(5 7 1% )。两者阳性率均随组织学分级升高而上升 ,但各级间未见明显差异 (P >0 .0 5 )。在转移组中 ,88.9% (2 4 /2 7)的病例C erbB 2过表达 ,85 .2 % (2 3/ 2 7)MMP2过表达 ,两者的过表达与转移呈正相关关系 (PC erbB 2 =0 .0 0 1,PMMP2 =0 .0 15 )。C erbB 2和MMP2阳性配对分析表明 ,两者间阳性表达互为正相关 (P <0 .0 0 5 ,r=0 .5 1)。结论 :在乳腺浸润性导管癌中 ,C erbB 2和MMP2的过表达提示转移增加 ,可以作为乳腺癌的预后指标。