Exogenous hormones and hereditary angioedema

Gonadal hormones, estrogen and androgen are strongly involved in the control of the bradykinin production. Estrogen may worsen whereas androgen can be part of the long-term prophylactic treatment. In this review, we will describe the potential impact of estrogen in the pathophysiology of hereditary angioedema (HAE). Then we will review the different hormone treatments and their implication on the course of HAE in women and men: contraception, Assisted Reproductive Technology (ART), menopause, hormone dependent cancers in women and men, treatment of hyperandrogenism in women.     

Effect of danazol-induced chronic hyperglucagonaemia on glucose tolerance and turnover

Abstract. It has been shown that danazol (14-ethinyl-testosterone) induces hyperglucagonaemia. To investigate the effect of chronic glucagon excess on carbohydrate metabolism, we studied six patients before and after treatment with danazol for immuno-thrombopenia. Glucose tolerance and insulin, C-pep-tide and glucagon secretion during an oral glucose tolerance test (oGTT) as well as peripheral and hepatic insulin sensitivity were determined by means of euglycaemic clamp technique (40mUm^-2 min^-1) before and after 3 months of danazol therapy. Overall glucose turnover (R₂) was assessed radioisotopically. (1) Plasma glucagon levels rose significantly from 88 ±16 pgmL^-1 before to 683 ± 148pgmL^-1 after therapy (P < 0.01). (2) Glucose levels during an oGTT were not significantly different before and after therapy. Glucose-stimulated insulin secretion at 60 and 120min and the area under the curve (AUC) for insulin during the oGTT. were significantly increased after danazol treatment compared with pre-treatment values (P < 0.05), whereas glucagon secretion showed a similar decrease at both time points of investigation (NS). (3) R_d during steady state showed a significant decrease during the entire period of euglycaemic clamp following therapy (after 240min, 3.8 ±0.6 vs. 5.3 ±0.7 mg kg^-1 min^-1, P < 0.05). The decline in glucagon during the clamp was similar during steady state before and after therapy. (4) Basal hepatic glucose output did not differ significantly before and after therapy (1.74 ±0.41 vs. 1.45 ±0.22 mg kg^-1, NS), whereas hepatic glucose output during the clamp was significantly less suppressed after danazol therapy. The authors conclude that chronic glucagon excess leads to a decrease in peripheral and hepatic insulin action which is accompanied by an increase in insulin secretion.     

环孢素联合达那唑治疗难治性特发性血小板减少性紫癜的疗效观察

目的探讨环孢素A(CSA)联合达那唑治疗难治性特发性血小板减少性紫癜(ITP)的临床效果。方法 45例难治性ITP患者随机分为两组,对照组(n=21例)给予长春新碱或环磷酰胺治疗,观察组(n=24例)给予CSA联合达那唑治疗,两组疗程均为3个月。治疗后比较两组疗效及不良反应发生率。结果观察组治疗总有效率(79.2%)明显高于对照组(66.7%),差异有统计学意义(P0.05);两组治疗期间不良反应发生率比较(45.8%vs.47.6%)无显著差异性(P0.05)。结论 CSA联合达那唑治疗难治性ITP疗效显著,安全可靠,值得临床推广应用。     

Danazol in acquired amegakaryocytic thrombocytopenic purpura: A case report

Summary Acquired amegakaryocytic thrombocytopenic purpura is a rare disease. Most reported patients did not respond to any therapeutical approach. Recently we observed a striking improvement of this disorder in a female patient shortly after therapy with danazol had been initiated. This observation and its possible implication for the treatment of amegakaryocytic thrombocytopenia are reported herein.     

Danazol Therapy in Immune Thrombocytopenic Purpura

Nine children with chronic refractory immune thrombocytopenic purpura and moderate to severe episodes of bleeding were treated with Danazol in an attempt to increase their platelet counts and improve clinical hemostasis. Only one patient experienced an excellent response while a good response was obtained in another. Cessation of bleeding episodes was observed in two other children with only marginal increases in platelet counts. Four of the nine patients failed to show any clinical or hematological improvement. The drug was well tolerated but its efficacy in childhood ITP needs further evaluation.     

60例子宫内膜异位症药物治疗的比较

目的 观察子宫内膜异位症患者用小剂量米非司酮联合孕三烯酮治疗以及单纯用孕三烯酮或达那唑治疗的临床效果、不良反应.方法 将60例确诊的子宫内膜异位症患者随机分为3组治疗：A组小剂量米非司酮加孕三烯酮治疗（26例）,B组单纯服孕三烯酮胶囊（20例）,C组用达那唑口服治疗（14例）.对比分析各组的治疗总有效率、不良反应.结果 A组治疗较B、C组总有效率明显增高,而不良反应明显减少,差异有统计学意义（P＜0.05）.结论 小剂量米非司酮联合孕三烯酮治疗子宫内膜异位症对减少月经量、减轻痛经症状好,而肝脏损害及出现痤疮等副反应少,其方法优于单纯用孕三烯酮或达那唑治疗,值得推广.     

Effects of Chinese Materia Medica-Fubao Danggui Jiao on experimental endometriosis

The objective of this paper was to investigate the effects of a Chinese Materia Medica variant -Fubao Danggui Jiao (FDJ)-on experimental endometriosis. An endometriosis model was created by virtue of auto-transplantation of endometrial tissue onto rats' abdominal walls. The implants were allowed to grow for 30 days until the successful completion of the model. After that, forty endometriotic rats were randomly divided into four study groups and given different treatments: (1) negative control group (water, 2ml/kg, per os); (2) FDJ-A group (FDJ, 2ml/kg, per os); (3) FDJ-B group (FDJ, 4ml/kg, per os); (4) Danazol group (70mg/kg, per os). After 30 days with treatments, the volumes of endometriotic implants in each rat were measured. The implants and normal uterine horns were removed for routine histological examination. FDJ caused significant decreases in volumes of the surviving endometriotic implants, with two different doses having statistically equivalent effects. Upon histological examination, FDJ was observed to cause regression of epithelium and stroma of endometriotic implants. FDJ had revealed promising therapeutic effects on endometriosis.     

重度子宫内膜异位症患者术后应用米非司酮与丹那唑的临床比较

目的 :研究不同方法在子宫内膜异位症治疗中的临床疗效与副反应。方法 :选择行保守性手术治疗后的卵巢子宫内膜异位症年轻患者 1 0 0例 ,随机分为 3组 ,试验 1组 33例 ,术后 1周开始口服米非司酮 1 2 5mg,每日 1次疗程 6个月 ;试验 2组 34例 ,术后 1周口服丹那唑2 0 0mg ,每日 3次 ,疗程为 6个月 ;对照组 33例 ,术后不采用药物治疗。所有患者均随访 36个月。结果 :三组治疗有效率分别是 87 88%、82 35 %、45 45 % ,试验 1组与试验 2组间无显著差异 (P >0 0 5) ,两试验组与对照组间差异显著 (P <0 0 1 ) ;妊娠率与复发率两试验组间无差异(P >0 0 5) ,两试验组与对照组间差异显著 (P <0 0 5) ;副反应中体重增加及谷丙转氨酶 (ALT)升高两项 ,试验组间差异显著 (P <0 0 5)。结论 :重度子宫内膜异位症的年轻患者行保守性手术后应用米非司酮或丹那唑能明显提高临床疗效与妊娠率 ,降低复发率 ,米非司酮与丹那唑疗效近似 ,但前者副作用低于后者。     

达哪唑衍生物的合成

Synthesis of danazol analogues involved transformation of 3-ketosteroids (Ⅰa～c) into 2-hydroxymethylene steroids (Ⅱa～c) and subsequent cyclization to steroidal (2, 3 d) isoxazoles (Ⅲa～c), Further treatment with sodium methoxide gave the corresponding steroidal-3-oxo-2α-carbonitriles (Ⅳa～c). The binding ability of (Ⅲa～c) and (Ⅳa～c) to progesterone receptor were examined and (Ⅲc) was found to be two times as active as danazol.