Drug action on poly(A) polymerase activity and isoforms during U937 cell apoptosis

The enzyme poly(A) polymerase (PAP; EC 2.7.7.19) catalyzes the polyadenylation of mRNAs. It's activity levels and isoforms vary within the cell cycle (31) and apoptosis (34). The direct effect of most anticancer drugs is cell damage (DNA and RNA synthesis inhibition, DNA breaks and/or cell cycle aberrations), which then triggers signaling pathways that activate apoptosis and eventually lead to regulated cell death. The experiments described here concern the chemotherapeutic agents, interferon (IFN) and 5-fluorouracil (5-FU), and their action on U937 cells, alone or in various combinations, resulting in the commitment of cell apoptosis, as observed by the appearance of DNA fragmentation. Furthermore, examination of U937 cell apoptotic trend in parallel with PAP activity measurements and isoforms detection by immunoblotting, revealed both partial enzyme inactivation and dephosphorylation, in particular after the combined drug action of 5-FU and IFN on U937 cells. Our work on chemotherapeutic drug action at the level of mRNA polyadenylation may contribute to new insights into the mechanism of cell apoptosis, as well as provide information on mRNA poly(A) tail formation, removal and function.     

Efficacy,safety and tolerability of green tea catechins in the treatment of external anogenital warts: a systematic review and meta‐analysis

Background External anogenital warts (EGWs) are non‐malignant skin tumours caused by human papillomavirus. They are one of the fastest growing sexually transmitted diseases. Current treatments are unsatisfactory. Green tea sinecatechin Polyphenon E ointment is a botanical extract from green tea leaves exhibiting anti‐oxidant, anti‐viral and anti‐tumour properties. Objective The aim of this study was to integrate valid information and provide basis for rational decision making regarding efficacy and safety of green tea extracts in the treatment of EGWs. Methods A systematic search in electronic databases was conducted using specific key terms. Main search was performed independently by two reviewers. The accumulated relevant literature was subsequently systematically reviewed and a meta‐analysis was conducted. Results Three randomized, double‐blind, placebo‐controlled studies evaluating efficacy and safety of Polyphenon E 15% and 10% in the treatment of warts were included in the systematic review and meta‐analysis. A total of 660 men and 587 women were enrolled. Regarding primary outcome, both Polyphenon E 15% and 10% demonstrated significantly higher likelihood of complete clearance of baseline and baseline and new warts compared with controls. No significant heterogeneity was detected. Recurrence rates were very low. Commonest local skin sign was erythema and local skin symptom was itching. Conclusions Efficacy of Polyphenon 15% and 10%, at least for the primary endpoint, is clearly indicated. Polyphenon E treatment exhibits very low recurrence rates and appears to have a rather favourable safety and tolerability profile. Recommendations for future studies should include evaluation of the efficacy of green tea catechins in the treatment of internal anogenital warts and direct comparison with its principal comparator, imiquimod.     

Deferoxamine decreases the excitatory amino acid levels and improves the histological outcome in the hippocampus of neonatal rats after hypoxia-ischemia.

Hypoxic-ischemic encephalopathy is a severe complication of perinatal asphyxia and causes lifelong deficits in infants and children. Multiple mechanisms acting in serial or parallel fashion are likely to be involved in this procedure. The neuronal injury is strongly related to iron-catalysed oxygen radical production and subsequent peroxidative damage to lipids and protein. Excessive release of excitatory amino acids (EAA) glutamate and aspartate, with consequent overstimulation of glutamate receptors, is also thought to be an important mechanism in this brain injury. Deferoxamine (DFO), a chelator of non-protein-bound iron, has been shown to inhibit lipid peroxidation and hydroxyl radical production via the Fenton reaction and to decrease hypoxic-ischemic and reperfusion associated brain injury. However, the exact mechanism of neuroprotection of DFO and its possible effect on the neurotransmitters' release is currently being investigated. In the present study, a well-established model of perinatal asphyxia was used to investigate the effect of DFO on hypoxic-ischemic-induced damage to different hippocampal brain structures. DFO was administrated subcutaneously immediately after the asphyctic insult. Histological examination of the hippocampus was conducted and the tissue levels of glutamate and aspartate in the same area were determined. A remarkable reduction of hypoxia-ischemia-evoked neurons in the CA1 hippocampal region and a decrease in the asphyxia-induced hippocampal tissue levels of glutamate and aspartate was noted after DFO treatment. These findings suggest a complex action of DFO, which could be neuroprotective when administrated in the immature brain immediately after hypoxia-ischemia.     

A Proposed Model of Relapse Prevention for Adolescents Who Abuse Alcohol

Adolescents who abuse alcohol are being admitted to treatment centers in increasing numbers. However, relapse prevention, a critical aspect of recovery, rarely is addressed in this high-risk population. This article briefly reviews adolescent development, the current literature on adolescent drinking patterns and relapse, and analyzes current models of relapse prevention in adults. This information is then used to propose a relapse prevention model for adolescents.     

肌腱玻璃化法冷冻保存的体外实验

目的:目前临床上常用低温冷冻法来保存同种异体肌腱,但操作较复杂费时,并且所保存的肌腱活性较低而限制其应用。采用已筛选的玻璃化法冷冻保存鸡屈趾深肌腱,并将复温后的玻璃化肌腱进行体外检测,探索其作为肌腱移植材料的可行性。方法:实验于2003-11/2005-02在解放军总医院骨科研究所完成。①实验材料及分组:来亨鸡16只,雄性,体质量2.5kg左右,随机分为2组,玻璃化组为玻璃化肌腱,新鲜肌腱组为新鲜肌腱,每组8只。②实验过程:切取来亨鸡屈趾深肌腱,置入玻璃化液内快速投入液氮保存2周制备玻璃化肌腱。③实验评估:将2组肌腱在体外进行大体、组织学及超微结构观察,羟脯氨酸含量测定,生物力学性能检测,并对两组肌腱进行细胞培养与鉴定。结果:①玻璃化组肌腱的大体、组织学及超微结构与新鲜肌腱组相似,其细胞及细胞外结构得以良好保存。②应用碱解法测定玻璃化肌腱内的羟脯氨酸含量为69.27mg/g,与新鲜肌腱组间差异无统计学意义。③玻璃化组肌腱破裂强度为165.58MPa,弹性模量1.41GPa,与新鲜肌腱组的力学性能差异无统计学意义。④将玻璃化组肌腱进行细胞培养,细胞第8天自组织块长出,第21天后传代,培养3代后出现明显的退化现象,其生物学特性与新鲜肌腱组相似。⑤将两组肌腱培养的细胞分别进行免疫组织化学染色,经鉴定均为肌腱细胞。结论:玻璃化法保存的肌腱具有良好的细胞活性、细胞外结构及力学性能,其生物学及生物力学特性无明显变异。     

EUROPEAN STROKE PREVENTION STUDY 2: DIPYRIDAMOLE AND ACETYLSALICYLIC ACID IN THE SECONDARY PREVENTION OF STROKE

In 1988, an optimal antiplatelet regimen for secondary stroke prevention remained to be defined. We undertook a randomised, placebo-controlled, double-blind trial to investigate the safety and efficacy of low-dose acetylsalicylic acid (ASA), modified-release dipyridamole, and the two agents in combination. Patients with prior stroke or transient ischaemic attack (TIA) were randomised to treatment with ASA alone (50 mg daily), modified-release dipyridamole alone (400 mg daily), the two agents in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death. TIA and other vascular events were secondary endpoints. Patients were followed on treatment for two years. We concluded that dipyridamole, in a modified-release form, at a dose of 200 mg b.d. and ASA 25 mg b.d., have been shown to be equally effective in the secondary prevention of ischaemic stroke and TIA; that when co-prescribed, the protective effects are additive, the combination being significantly more effective than each agent prescribed singly; and that low-dose ASA does not eliminate the propensity for induced bleeding.