哺乳期避孕药ST-1435衍生物的合成

19-失碳-16-亚甲基-17α-乙酰氧基黄体酮(3)最早由我国合成,后来西德E.Merk AG药厂使其开发成高效低毒的非口服避孕药,称ST-1435,其皮下埋植缓释系统国外已临床使用,有效避孕期约一年,临床研究还发现它对脂代谢、糖代谢、内分泌与肝功能等均无不良影响,并因其口服无效,近年来国外认为它更适合于哺乳期妇女使用。     

Insulin-like growth factor binding protein 1 response to acute insulin induced hypoglycaemia in Type 1 diabetes

OBJECTIVES Insulin Is believed to be the prime regulator of Insulin-like growth factor binding protein 1 (IGFBP-1) secretion, and In normal subjects acute insulin Induced hypoglycaemla exerts a rapid effect on concentrations of IGFBP-1, and may also Influence Insulin-like growth factor I (IGF-I) concentrations. The rise In IGFBP-1 concentrations in normal subjects following hypoglycaemia has been suggested to be due to suppression of endogenous insulin secretion. We have examined this further by studying diabetics with no endogenous Insulin secretion. DESIGN We have compared the IGFBP-1 response to acute insulin Induced hypoglycaemia in normal subjects and patients with Type 1 (insulin dependent) diabetes mellitus. METHODS Insulin tolerance test8 were performed using a bolus of Insulin (0·15 U/kg), in six control subjects and six patients with Type 1 diabetes. MEASUREMENTS Serum levels of IGFBP-1, insulin, glucose, and IGF-I were measured at regular Intervals during the insulin tolerance test. RESULTS Blood glucose fell to a nadir which coincided with the onset of the acute autonomic reaction ‘R’ In both groups. The basal concentration of IGF-I was significantly lower In the diabetic group at 0·4 ± 0·1 kU/l, compared to 0·9 ± 0·1 kU/l In the control group, but there was no significant change In IGF-I concentrations In response to hypoglycaemia In either group. Hypoglycaemia provoked a fall In IGFBP-1 In patients with Type 1 diabetes, from 38 ± 9 μg/l basally to 17 ± 3 μg/l at R + 120 minutes, with a return to basal values of 45 ± 11 μg/l at R + 180 minutes. In the control subjects there was no fall In IGFBP-1, but a significant Increase to 71 ± 14 μg/l at R + 180 minutes. CONCLUSION This difference In the IGFBP-1 response In the presence of a similar glucose response suggests that In Type 1 diabetes there may be different sensitivities to the actions of exogenous Insulin on IGFBP-1 regulation.     

The effect of omeprazole on insulin induced gastric secretion in man

The effect of oral omeprazole on insulin induced gastric secretion was studied in 12 healthy subjects. Each subject participated in two secretory tests receiving an intravenous infusion of insulin (0.03 units/kg/h) and being randomly allocated to receive 30mg or 60mg omeprazole suspended in 100ml water containing 16 mmol NaHCO3 on the second study day. Peak plasma concentrations of omeprazole were achieved within 30 minutes of administration in all but one subject and plasma half life was 30 minutes. Mean peak stimulated acid output in the six subjects receiving 30mg omeprazole was reduced to 4.3 +/- S.E. 1.8 mmol/h from a control value of 16.8 +/- 2.2 mmol/h (p less than 0.05) and in six subjects receiving 60mg omeprazole, mean peak output fell to 3.4 +/- 2.1 mmol/h from a control value of 12.3 +/- 2.6 mmol/h (p less than 0.05). The two doses of omeprazole produced similar reduction in acid secretion (74% and 73% respectively) but neither dose affected pepsin secretion. Both doses of omeprazole were associated with a small statistically insignificant increase in the plasma gastrin response to insulin infusion.     

Acute lymphoblastic leukemia in infants: evidence for B cell origin of disease by use of monoclonal antibody phenotyping

Since the prognosis of infants with acute lymphoblastic leukemia (ALL) is so poor, it has been suggested that these leukemias may not be lymphoid in origin, but may originate from stem cell, myeloid, or megakaryocytic progenitors. Alternately it has been hypothesized that these leukemias originate in lymphoid cells at the earliest stages of B cell development. Another possibility is that these leukemias may be of more than one lineage. Therefore we examined leukemic blasts from 12 infants with ALL using monoclonal antibodies to myeloid and lymphoid differentiation antigens. The majority of specimens expressed HLA/DR and reacted with B4 (CD19) but failed to react with stem cell, myeloid, megakaryocytic, or T cell associated antibodies. These results support the speculation that the majority of these leukemias arise in cells at the earliest stages of B cell commitment, and are not of a myeloid or biphenotypic nature.     

苯甲酰胺类抗精神病药物的研究:若干3α-去甲托品烷衍生物的合成

Reductive amination of8- benzyl-nortropinone(3 )with ammonium acetate andsodium cyanoborohydride yielded the 3 α-amino nortropane derivative 4 which was condensed withsubstituted benzoic acids using 2-bromo-N-methyl-pyridinium iodide as condensing reagent to give thetarget compounds 2a～ein an overall yield of 50～60%.Compound 2e showed marked and selectiveaffinity for D-2 receptor.Compound 2d showed definite affinity for D- 1 receptor besides markedaffinity for D-2 receptor.     

Head and neck MR imaging in the pediatric patient

Magnetic resonance (MR) imaging studies of the head and neck (excluding the brain) were obtained in 49 children believed to have lesions of the head and neck. Seven children had normal images; in the remaining 42, lesions were divided into four categories: midline lesions, lesions of symmetric paired structures, facial lesions, and nasopharyngeal and oropharyngeal lesions. All entities were well delineated by MR imaging. The imaging planes and sequences chosen depended on the suspected abnormality. Midline lesions were best imaged in the sagittal plane, lesions of paired structures and the face in the axial or coronal planes, and nasopharyngeal and oropharyngeal lesions in the axial or sagittal planes. Intracranial extension of head and neck neoplasms was best evaluated in the coronal plane. Surface coils provided better resolution and were thus more useful in evaluating small superficial lesions; head or body coils were more useful in defining the extent of large lesions. T2-weighted images provided better differentiation between normal and tumor tissue in patients with head and neck neoplasms.     

Androgenic status and sexual function in males with rheumatoid arthritis and ankylosing spondylitis

The pituitary-testicular axis was investigated in 31 males with rheumatoid arthritis (age range 19-60 years, median 55 years) and 33 males with ankylosing spondylitis (age range 22-55 years, median 37 years) and compared with a control group of 95 normal male volunteers. Using analysis of covariance, patients with rheumatoid arthritis showed significantly lower serum testosterone (p less than 0.05) and derived free testosterone (p less than 0.01) concentrations and significantly higher serum LH and FSH concentrations (p less than 0.05) compared with controls. All patients had normal serum prolactin and cortisol concentrations. Serum testosterone correlated with ESR, haemoglobin concentrations and rheumatoid factor titres (r = -0.448, p less than 0.02; r = 0.440, p less than 0.02; r = -0.360, p less than 0.05 respectively) in the rheumatoid patients. Although there was a significant negative correlation between ESR and haemoglobin concentrations (p less than 0.005) in the patients with ankylosing spondylitis, neither variable correlated with serum testosterone concentrations. There was no association between testicular dysfunction and the presence of extra-articular features of rheumatoid arthritis. Ten patients (33 per cent) with rheumatoid arthritis and four (13 per cent) with ankylosing spondylitis admitted to periods of impotence while 15 (50 per cent) of the former and 12 (39 per cent) of the latter had periods of decreased libido. There was no evidence for increased rates of infertility in either group.     

苦红菇化学成分的研究

从野生真菌苦红菇(Russula rosacea(Bull)Grrayem,Fr.)子实体酸性部分得到两个新的四环三萜酸化合物,经光谱(IR,¹HNMR,¹³CNMR,MS)、尤其是二维核磁共振(¹³C-¹HCOSY,COLOC,NOEDIFF)谱解析,确定其结构分别如Ⅰ和Ⅱ所示,Ⅰ命名为苦红菇酸A(rosaceaacidA),Ⅱ为苦红菇酸B(rosaceaacidB)。     

苦参碱的人体药代动力学

建立了人血清苦参碱的高效液相色谱分析方法,此法回收率为99.1～102.2%,日内精密度RSD<4%,日间RSD<6%。血药浓度在1.25～40.0μg·mL^-1范围内呈线性关系(r=0.9997)。8名健康志愿者iv苦参碱6ms·kg^-1后,药代动力学过程符合二室模型。收集其中6名志愿者尿液,32h尿中原形药物排泄率为52.75%,肾清除率为143.79ml·min^-1。