抗消化性溃疡病药物杂环甲醛缩氨(硫)脲和酰胺的合成和构效分析

呋喃唑酮是我国临床上发现并使用的抗消化道溃疡药物。为优化其活性,对呋喃唑酮分子中的硝基呋喃环和噁唑酮环进行了结构修饰和改造。合成的28个化合物的生物活性表明,用呋喃、噻吩、吡咯或甲基吡咯代替硝基呋喃环,用氮脲、氨硫脲和芳酰肼等结构片断替代噁唑酮环,均可引起活性和毒性的变化。构效关系分析表明,化合物的水溶解性和羰基的电荷密度是影响化合物活性的重要因素。     

消旋15（R）－15－甲基PGE_2甲酯的合成

消旋１５（Ｒ）－１５－甲基ＰＧＥ＿２甲酯的合成金碧燕，吴元鎏，张守仁，徐瑞明（中国医学科学院、中国协和医科大学药物研究所，北京１０００５０）前列腺素是一类存在于人体内，有广泛生理活性的重要内源性物质。ＰＧＥ衍生物已被证实除有抑制胃酸及胃泌素分泌的作用...     

吡咯-2-甲醛缩N4-(4-甲氧基苯基)氨基脲抗实验性大鼠溃疡作用

化合物Ⅰ具有与呋喃唑酮相似的抗实验性大鼠溃疡活性,但小鼠口服急性毒性较后者小。化合物Ⅰ在剂量为40～100 mg/kg时对五种大鼠溃疡模型(消炎痛型、幽门结扎型、慢性醋酸型、和无水乙醇引起的大鼠溃疡模型)均有较好保护作用,但对水拘急性应激型溃疡无效。对胃酸分泌无明显影响,对胃蛋白酶分泌有轻度抑制作用;具有“细胞保护”样作用,对HCl和无水乙醇引起的大鼠溃疡显示出较好的保护作用;增加幽门结扎大鼠胃液中氨基己糖的含量,降低DNA含量。     

Aromatase mRNA expression in individual follicles from polycystic ovaries

Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterized by arrested follicular development prior to selection of a dominant follicle. Dominant follicles produce large amounts of oestradiol but PCOS follicles do not. With several potential aromatase (P450AROM) inhibitors in follicular fluid, the question arises whether P450AROM is expressed in PCOS granulosa cells, but the activity is inhibited, or whether P450AROM is not expressed in PCOS. The purpose of the present study was to determine whether P450AROM mRNA expression is altered in PCOS and to correlate P450AROM mRNA expression in individual follicles with aromatase stimulatory bioactivity and oestradiol in the follicular microenvironments. P450AROM mRNA was measured in individual follicles from 16 PCOS and 48 regularly cycling control women by quantitative polymerase chain reaction (PCR) and correlated with follicular fluid oestradiol concentrations and aromatase stimulating bioactivity measured by the rat granulosa cells aromatase bioassay. Follicular fluid oestradiol was low in all control follicles <7 mm in diameter. Some follicles > or = 7 mm contained elevated oestradiol values (P < 0.01) and all had an androstenedione:oestradiol ratio of <4. Only in granulosa cells from follicles > or = 7 mm with an androstenedione:oestradiol ratio of <4 were P450AROM mRNA levels increased (P < 0.05). These same follicles also contained increased levels of aromatase stimulating bioactivity whereas follicles <7 mm or with androstenedione:oestradiol ratio of >4 contained little or no bioactivity. All PCOS follicles contained low levels of oestradiol, P450AROM mRNA and aromatase stimulating bioactivity similar to size- matched control follicles. These data indicate that P450AROM mRNA expression and oestradiol production begin in developing follicles when they reach approximately 7 mm in diameter. Oestradiol production is low in PCOS follicles because there is insufficient aromatase stimulating bioactivity to increase P450AROM mRNA expression.      

Combined treatment with enuresis alarm and desmopressin for nocturnal enuresis

Seventy-one children with nocturnal enuresis were enrolled in a controlled trial. The children were allocated to two matched groups. Children in both groups used an enuresis alarm until the end of treatment. Children in the first group were treated with 40/^g of intranasal desmopressin (Desmospray) for up to 6 weeks at the start of treatment with the alarm. During the observation period before treatment there were 2.3 dry nights per week in both groups. At the end of treatment there was a significant difference in the mean number of dry nights per week between the two groups (6.3 in the alarm and desmopressin group and 4.8 in the alarm group) and also in the number of children becoming reliably dry. The combination of desmopressin and alarm was particularly helpful for children with severe wetting and those with family and behavioural problems. Desmopressin, enuresis alarm, nocturnal enuresis
MG Bradbury, Department of Paediatrics and Child Health, St James's University Hospital, Leeds LS9 7TF, UK     

Etheno adducts in spleen DNA of SJL mice stimulated to overproduce nitric oxide

In order to investigate specific DNA damage caused by nitric oxide (NO) induced lipid peroxidation, levels of promutagenic etheno adducts 1,N6- ethenodeoxyadenosine (epsilondA) and 3,N4-ethenodeoxycytidine (epsilondC) were measured in spleen DNA of SJL mice induced to produce high levels of NO by injection of RcsX (pre-B-cell lymphoma) cells. epsilondA and epsilondC levels were quantified by an ultrasensitive immunoaffinity-32P-post-labeling method. Spleen DNA of control mice (n = 5) had background levels of 9.2+/-5.4 epsilondA adducts per 10(9) dA and 13.1+/-5.7 epsilondC adducts per 10(9) dC. In RcsX cell-injected mice (n = 7), levels of these adducts were elevated approximately 6- fold, i.e. 53.9+/-39.4 epsilondA per 10(9) dA and 83.5+/-57.8 epsilondC per 10(9) dC (P < 0.05). Mice injected with RcsX cells and also treated with NG-methyl-L-arginine (NMA), an inhibitor of inducible nitric oxide synthase (n = 6), had significantly reduced levels (P < 0.05) of both epsilondA and epsilondC (13.5+/-5.7 epsilondA per 10(9) dA and 28.2+/- 15.7 epsilondC per 10(9) dC). These findings constitute the first available evidence of formation of etheno adducts associated with NO overproduction in vivo. The adducts were presumably formed from lipid peroxidation products such as trans-4-hydroxy-2-nonenal (HNE), generated via oxidation of lipids by peroxynitrite. The results suggest that etheno-DNA adducts, among other types of damage, may contribute to the etiology of cancers associated with chronic infection/inflammation in which NO is overproduced.      

Precipitants and aetiology of cyclic vomiting syndrome

Thirty-two patients aged 2-22 y with cyclic vomiting syndrome (CVS), and 64 age- and gender-matched controls were assessed to determine the nature, severity, precipitants and associated features of attacks and the incidence of potential aetiological factors. The mean age of onset was 3.5 y. Patients experienced a mean of nine attacks per year, of average duration 2.4 d, and two-thirds missed more than 10 d of school per year. Patients were more likely to have migraine and co-ordination difficulties, a past history of forceps delivery and gastroesophageal reflux than controls. Compared with controls, subjects had a higher incidence of psychological symptoms (38% compared with 19%) and migraine (37% compared with 9%). CVS is a chronic, disabling condition and is a migraine variant, with attacks usually precipitated by stress and intercurrent infections.     

Early child health in Lahore, Pakistan: IX. Perinatal events

In Pakistan there are a number of acute problems related to maternal and infant health in the perinatal period. There is also lack of reliable data needed for the formulation of action strategies. To provide a database 1490 women have been followed from the 5th month of pregnancy in four different areas at various levels of urbanization and socio-economic development. After adjusting for gestational age, the proportion of newborns with weight for length < -2SDS in relation to the Swedish National Standard was 12–31% for boys and 12–25% for girls, the figure being highest in the most deprived area. Preterm birth was infrequent compared with IUGR. The overall prevalence rate of birth defects was 21% out of which 8% were severe defects. The overall perinatal mortality rate was 56/1000 births, with rates of 60, 75, 36 and 33/1000 births for the village, periurban slum, urban slum and the upper middle class. Two thirds of the deaths were related to either a continuation of intrauterine disturbances or severe congenital defects incompatible with life. One third of the deaths were due to infection; mostly diarrhoea, clinical sepsis and ARI. Neonatal mortality was significantly related to birth length (<-2SDS, odds ratio 5.5) and length of gestation (<37 weeks, odds ratio 5.6) and was to a lesser extent related to weight (<-2SDS, odds ratio 2.0) and weight for length (<-2SDS, odds ratio 1.3). Forty percent of the mothers had weight for height below -2SDS, 23–35% had height <-2SDS. Forty percent of mothers from a subset within the cohort had a hemoglobin < 10 gm/dl and 20% showed signs of pre-eclampsia. This presentation raises the issue of expanding the current Child Survival Programs into the perinatal period as well.