N-(6,6-二甲基-2-庚烯-4-炔基)-N-甲基-α-取代-1-(4-取代)萘甲胺类的合成及抗真菌活性

根据氮唑类和烯丙胺类抗真菌化合物的构效关系、作用机理。设计合成了30个N-(6,6-二甲基-2-庚烯-4-炔基)-N-甲基-α-取代-1-(4-取代)萘甲胺类化合物。初步体外抑菌试验结果表明,大多数目标化合物对八种试验菌株都有不同程度的抗真菌活性。化合物Ⅰ_1a的真菌活性大致与克霉唑相当,对白念珠菌的活性明显高于naftifine和terbinafine,但对其它七种菌株的活性均不及naftifine和terbinafine;化合物Ⅲ_1a对八种试验菌株的活性均与terbinafine相当。     

Spontaneous Apoptosis of Endometrial Tissue is Impaired in Women with Endometriosis

Objective: To evaluate spontaneous apoptosis in single-cell suspensions of eutopic and ectopic endometrium from women with endometriosis and in eutopic endometrium from fertile controls without endometriosis.

Design: Paired specimens of eutopic and ectopic endometrial tissue from patients with endometriosis and eutopic endometrium from controls were assessed for spontaneous apoptosis.

Setting: Institute for the Study and Treatment of Endometriosis and university-based research laboratories.

Patient(s): Fertile controls (n = 10) and women with untreated endometriosis (n = 16).

Intervention(s): None.

Main Outcome Measure(s): Spontaneous apoptosis assessed with an ELISA-based cell death detection kit.

Result(s): Spontaneous apoptosis (monitored by absorbance) of eutopic endometrium from patients with endometriosis and fertile controls was 0.63 ± 0.1 and 1.43 ± 0.11, respectively. Among patients with endometriosis, spontaneous apoptosis of ectopic endometrium was 0.26 ± 0.06. Decreased apoptosis of ectopic versus eutopic endometrium was observed independent of cycle phase.

Conclusion(s): The susceptibility of endometrial tissue to spontaneous apopoptosis is significantly lower in women with endometriosis than in fertile controls. We suggest that decreased susceptibility of endometrial tissue to apoptosis contributes to the etiology or pathogenesis of endometriosis.     

Delayed ovarian response in oligomenorrheic women using gonadotropin-releasing hormone agonist.

Ovarian response to human menopausal gonadotropins (hMG) was studied in the presence or absence of prior ovarian suppression using gonadotropin-releasing hormone agonist in the same oligomenorrheic women. Delayed response, with higher hMG requirements, was observed in cycles with prior ovarian suppression.     

Absence of mutations in the transforming growth factor-beta type II receptor in sporadic lung cancers with microsatellite instability and rare H-ras1 alleles

The transforming growth factor-beta type II receptor (RII) is commonly mutated in colon and gastric cancers with microsatellite instability (MI). We utilized our series of lung cancers with MI and rare alleles of the H-ras1 gene to determine the association between MI and RII mutations and searched the entire RII coding region in 33 lung cancers with MI by polymerase chain reaction-single-strand conformation polymorphism analysis. We found no mutations, and these data support other recent evidence that RII mutations rarely occur except in colon and gastric tumors with MI.      

藻酸钠复合自体软骨细胞修复猪关节软骨缺损的近期效果

目的:采用藻酸钠自体软骨细胞混合物修复猪的关节软骨缺损,观察近期成骨效应。方法:实验于2004-03/2005-04在中山大学附属第二医院实验中心完成。3个月龄的小型猪8只,取其关节软骨进行细胞原代培养,获取原代细胞后,分别进行免疫组织化学法检测细胞Ⅱ型胶原表达。然后对8只小型猪的32个关节进行动物关节缺损的模型建立,每个关节共造3个人工缺损,选择关节左右随机对照。将已经培养好的软骨细胞与已经配制好并消毒的藻酸钠混合,移植到猪的关节软骨缺损处。每只猪关节内注射3个实验点,1个用藻酸钠/细胞混合液为实验组,1个单纯支架材料为单纯材料对照组,1个缺损做空白对照组,模型中缺损区均为关节负重区,胶原纤维绿色(亮绿复染)。修复所用细胞为自体软骨体外培养后,进行移植修复,采用3代体外培养软骨细胞,均匀混和藻酸钠后,行自体移植。8周后取实验关节进行大体观察、苏木精-伊红染色、Masson染色、免疫组织化学法染色观察及O’driscoll组织学评分。结果:纳入小型猪8只,除其中1例因手术切断伸直肌腱而使猪关节活动障碍,其余均未见手术后关节活动障碍,所有手术无术后感染,无关节内感染,无动物死亡。移植的软骨细胞在藻酸钠载体中生长良好,形成透明软骨。根据O’driscoll组织学评分标准,实验组32个猪关节缺损修复的组织学评分为(20.25±1.64)分,高于单纯材料对照组的(7.46±1.29)分及空白对照组的(6.00±2.09)分。免疫组织化学染色可见修复软骨以表达Ⅱ型胶原为主,无Ⅰ型胶原。结论:藻酸钠复合自体软骨细胞作为软骨移植的替代物是可行的,远期效果还有待进一步研究。     

Deficiency of platelet membrane glycoprotein Ia associated with a decreased platelet adhesion to subendothelium: a defect in platelet spreading

A bleeding disorder with absent collagen-induced platelet aggregation and adhesion has been described in a patient whose platelets failed to express surface glycoprotein Ia. We studied the interaction of her platelets with subendothelium in an annular perfusion chamber and the interaction with purified human collagen type III in a rectangular perfusion system under flow conditions. Platelet adherence was almost completely absent both at low and high shear rates. The few platelets which adhered remained in the contact stage without subsequent spreading and aggregate formation. Addition of a monoclonal antibody, which was directed against the von Willebrand moiety of FVIII-VWF, to the blood, completely abolished platelet adherence at high shear rates and had a partial effect at low shear rates. These data indicate that von Willebrand factor plays a role in the initial attachment (contact stage) of platelets to subendothelium. We conclude that the bleeding disorder and excessively prolonged bleeding time in our patient are caused by a new specific defect of the platelet-vessel wall interaction.