Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory skin edema and ornithine decarboxylase activity by theaflavin-3,3'-digallate in mouse

Among black tea polyphenols, theaflavins were generally considered to be the most effective in cancer chemoprevention. In this study, we examined the inhibitory effects of black tea polyphenols, including theaflavin (TF-1), a mixture (TF-2) of theaflavin-3-gallate and theaflavin-3'-gallate, theaflavin-3,3'-digallate (TF-3), and the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema and ornithine decarboxylase (ODC) activity. Topical application of these polyphenols onto the mouse resulted in inhibition of TPA-induced ear edema and skin epidermal ODC activity. The inhibitory order was as follows: TF-3 > TF-2 approximately equal to EGCG > TF-1. Western and Northern blots indicated that TF-3 significantly reduced the protein and mRNA levels of ODC in TPA-treated mouse skin and NIH 3T3 cells, whereas EGCG showed less activity. EGCG and TF-3 were able to inhibit the ODC enzyme activity in vitro. Furthermore, TF-3 also significantly reduced the basal promoter activity of the ODC gene in NIH 3T3 cells that were transiently transfected with ODC reporter plasmid. These results suggested that TF-3 was a potential inhibitor of ODC activity and TPA-induced edema and might be effective in cancer chemoprevention.     

放免法测定746例地戈辛血药浓度分析

目的：监测地戈辛血药浓度。方法;采用放免法监测７４６例地戈辛治疗慢性心功能不全病人的血药浓度。结果;血药浓度在治疗范围者３２５例,偏低者９９例,高者３２２例,大于治疗范围者中有１２例出现中毒症状。结论：监测地戈辛血药浓度可作为判断药物疗效和中毒的客观指标。     

Enhanced spontaneous transmitter release at murine motor nerve terminals with cyclosporine

Cyclosporine, a calcineurin inhibitor, significantly enhances spontaneous acetylcholine release after a brief tetanus and potentiates the effect of phorbol 12,13-dibutyrate. Both actions are prevented by the protein kinase C inhibitor, bisindolylmaleimide iodide. Protein kinase C and calcineurin thus play important roles in the balance between phosphorylation and dephosphorylation regulating spontaneous transmitter release at motor nerve terminals.     

COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer

Extensive documentation has validated the role of UV irradiation as a tumor initiator and promoter, inducing both squamous and basal cell carcinomas. Human epidermis is a tissue which undergoes active metabolism of arachidonic acid to prostaglandins which is regulated by the action of prostaglandin H synthase (also known as cyclooxygenase). One mechanism for the promotional activity of UV light may involve its ability to induce prostaglandin formation. Work in our laboratory has demonstrated that acute exposure of human keratinocytes to UVB irradiation results in increased production of prostaglandin E2 (PGE2). When cultured human keratinocytes were examined after irradiation with 30 mJ/cm2 UVB in vitro, Western blot analysis showed a 6-fold increase in COX-2 protein which was evident at 6 h and peaked 24 h after irradiation. Furthermore, when human subjects were irradiated on sun- protected skin with up to four times their minimal erythema dosage (MED) and biopsied 24 h later, upregulation of COX-2 protein expression was observed via immunofluorescence microscopy. RNAase protection assays supported this observation, showing induction of COX-2 message which peaked at approximately 12 h following irradiation in vitro. Furthermore, human squamous cell carcinoma biopsies exhibited strongly enhanced staining for COX-2 protein via immunohistochemistry and Western analysis when compared to normal non-sun-exposed control skin. Together, these data demonstrate acute upregulation of COX-2 via UVB irradiation and suggest the need for further studies of COX-2 expression as a potential pharmacological target mediating human skin tumor development.      

A ninth locus (RP18) for autosomal dominant retinitis pigmentosa maps in the pericentromeric region of chromosome 1

We studied a large Danish family of seven generations in which autosomal dominant retinitis pigmentosa (adRP), a heterogeneous genetic form of retinal dystrophy, was segregating. After linkage had been excluded to all known adRP loci on chromosomes 3q, 6p, 7p, 7q, 8q, 17p, 17q and 19q, a genome screening was performed. Positive lod scores suggestive of linkage with values ranging between Z = 1.58-5.36 at theta = 0.04-0.20 were obtained for eight loci on proximal 1p and 1q. Close linkage without recombination and a maximum lod score of 7.22 at theta = 0.00 was found between the adRP locus (RP18) in this family and D1S498 which is on 1q very near the centromere. Analysis of multiply informative meioses suggests that in this family D1S534 and D1S305 flank RP18 in interval 1p13-q23. No linkage has been found to loci from this chromosomal region in six other medium sized adRP families in which the disease locus has been excluded from all known chromosomal regions harbouring an adRP gene or locus suggesting that there is (at least) one further adRP locus to be mapped in the future.      

DNA diagnosis of FRAXA and FRAXE in Chinese children with neurodevelopmental disorders and fragile X syndrome

Fragile X (FraX) syndrome is the most common cause of inherited mental retardation. To see whether FRAXA or FRAXE can account for the etiology of some unexplained neurodevelopmental disorders in children, we screened for trinucleotide repeat expansion in a consecutive cohort of 73 Chinese children and their mothers seen in 1995 (group 1) referred for developmental assessment due to developmental delay, language delay, attention deficit hyperactivity disorder, autistic spectrum disorder, mental retardation and/or learning disability. We also screened DNA samples of all five previously diagnosed cytogenetically-positive FraX boys, their mothers and sisters (group 2). A control group of unrelated teenagers and adults were recruited from the community (group 3). In group 1, 3 families (2 mothers and a mother and her son) were found to carry a small premutation allele at FRAXA (premutation frequency = 2%, 3/153 independent X chromosomes), but none had any expansion at FRAXE. In group 2, all 5 FraX boys had full mutation at FRAXA and normal repeat length at FRAXE. In group 3, 1 male has a premutation allele out of 18 males and 59 females tested (premutation frequency of control = 0.7%, 1 out of 136 X chromosomes). For FRAXE screening in group 3, 2 females were carriers (1.5%, 2 out of 136 X chromosomes). Thus, FRAXA and FRAXE cannot account for the etiology of neurodevelopmental disorders in our cohort of Chinese children, and the prevalence of FRAXE mutation in normal Chinese population appears to be higher than reported in the Caucasians.     

中国香港与西方儿童分泌性中耳炎发病率的比较

目的 调查中国香港儿童分泌性中耳炎发病率,并且进一步与西方的研究结果做比较。方法 1995-1998年,在中国香港特别行政区随机抽取小学、幼稚园(4-5岁)及幼儿园(2-3岁),对6872名2-7岁儿童进行检查,在校内接受由耳鼻咽喉科专家施行的耳镜检查及由听力学家执行的鼓室导抗测试。为了与西方研究结果作出标准化的比较,根据他们所采用的诊断标准重新计算。结果 在划分为2-3岁、4-5岁及6-7岁的研究对象中,若以耳镜临床诊断作标准,本研究分泌性中耳炎发病率为5.2％-21.6％;若以鼓室导抗图作诊断标准,发病率为7.3％-30.7％。同一组数据,发病率计算结果是会因为采用不同的鼓室导抗图诊断定义而有偏差,但无论是用哪种方法,结果都与西方同龄研究的发病率差异无显著性,而且发病率随年龄增加而下降。结论 香港2-3岁、4-5岁,及6-7岁中国儿童的分泌性中耳炎发病率与西方文献报告没有显著性差异。