Quinonic derivatives active against <Emphasis Type="Italic">Toxoplasma gondii</Emphasis>

Quinonic derivatives were tested against a virulent RH strain of Toxoplasma gondii maintained in cell culture in THP-1, a human myelomonocytic cell line. The derivatives were tested at various doses (0.5-4 microg/ml) and compared with the reference molecules clindamycine, sulfadiazine, pyrimethamine and atovaquone. The percentage of parasite growth inhibition was observed after 72 h of incubation. The tested derivatives are bicyclic, tricyclic or tetracyclic quinones. Eight of these compounds exhibit over 70% inhibition of parasite growth; and two were nearly equipotent to pyrimethamine. These data indicate that the most active compounds against the RH strain of T. gondii are bis-heterocyclic quinones.     

Cardiopericardial Hydatid Cysts

apd: 18 December 2000     

Male pseudo-hermaphroditism due to partial 5 alpha-reductase deficiency, a case report

Male pseudo hermaphroditism caused by steroid 5 alpha reductase deficiency is a rare autosomal recessive disorder. This enzyme catalyses the conversion of testosterone to dihydrotestosterone (DHT) in genital tissue. The potent androgen DHT is required for full masculinization of the external genitalia hence, masculinization defects of varying degree result from diminished DHT formation. We report a Tunisian patient who was raised as a girl, presented to us at the age of 15, because male phenotype had become predominant at puberty. Endocrinological investigations revealed an in crease in the ratio serum testosterone/DHT = 17. Treatment with dihydrotestosterone and surgical correction, after psychological evaluation permitted the change of gender identity to male.     

Lack of association between single polymorphic variants of the mitochondrial nicotinamide adenine dinucleotide dehydrogenase 3, and 4L (MT-ND3 and MT-ND4L) and male infertility

Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%–30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT-ND3 and MT-ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT-ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT-ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT-ND3 and MT-ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT-ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT-ND3 and MT-ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation.     

定量组织速度显像技术测定二尖瓣环运动与左室整体收缩功能的评价

目的 :应用超声定量组织速度显像 (QTVI)技术测定二尖瓣环运动速度 ,评价其是否与左室整体收缩功能指标左室射血分数 (L VEF)相关。方法 :5 0例冠状动脉疾病患者 (冠心病组 )和 2 5例正常人 (对照组 ) ,从心尖四腔、两腔和长轴切面观中测定后间隔、侧壁、前壁、下壁、前间隔和后壁六个部位的二尖瓣环收缩期平均峰值速度 (Sm)以及心电图 QRS波起始至二尖瓣环收缩波峰值的时间 (Q- Sm) ,并与心尖四腔观单平面改良 Simpson法所测 L VEF作相关性分析。结果 :冠心病组六个部位的二尖瓣环 Sm平均值 (5 .2 1± 1.12 ) cm / sec与 L VEF呈显著正相关 (r=0 .6 6 ,P<0 .0 0 0 1) ,对照组六个部位的 Sm平均值 (6 .0 2± 0 .83) cm/ sec亦与 L VEF显著正相关 (r=0 .6 5 ,P<0 .0 0 0 1)。 Q- Sm和心率则与 L VEF无显著相关性。结论 :应用 QTVI技术测定收缩期二尖瓣环运动可反映左室整体收缩功能 ,有一定临床应用价值     

A Src/Abl kinase inhibitor, SKI-606, blocks breast cancer invasion, growth, and metastasis in vitro and in vivo

The central role of Src in the development of several malignancies, including breast cancer, and the accumulating evidence of its interaction with receptor tyrosine kinases, integrins, and steroid receptors have identified it as an attractive therapeutic target. In the current study, we have evaluated the effect of a Src/Abl kinase inhibitor, SKI-606, on breast cancer growth, migration, invasion, and metastasis. Treatment of human breast cancer cells MDA-MB-231 with SKI-606 caused a marked inhibition of cell proliferation, invasion, and migration by inhibiting mitogen-activated protein kinase and Akt phosphorylation. For in vivo studies, MDA-MB-231 cells transfected with the plasmid encoding green fluorescent protein (GFP; MDA-MB-231-GFP) were inoculated into the mammary fat pads of female BALB/c nu/nu mice. Once tumor volume reached 30 to 50 mm(3), animals were randomized and treated with vehicle alone or 150 mg/kg SKI-606 by daily oral gavage. Experimental animals receiving SKI-606 developed tumors of significantly smaller volume (45-54%) compared with control animals receiving vehicle alone. Analysis of lungs, liver, and spleen of these animals showed a significant decrease in GFP-positive tumor metastasis in animals receiving SKI-606 at a dose that was well tolerated. Western blot analysis and immunohistochemical analysis of primary tumors showed that these effects were due to the ability of SKI-606 to block tumor cell proliferation, angiogenesis, growth factor expression, and inhibition of Src-mediated signaling pathways in vivo. Together, the results from these studies provide compelling evidence for the role of Src inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.