Influence of environmental and genetic factors on variation in human response to DNA damaging agents

Exogenous DNA damaging agents must be considered in the context of endogenous reactive species which have the potential to damage DNA. Although a no-effect level for a DNA-damaging compound may not exist, it may be feasible to define a level where reducing exposure to the compound is no longer the most effective way of reducing human risk. Modifying environmental factors which affect human response to damage may be the better strategy. Although a number of rare human syndromes are associated with a reduced ability to repair DNA damage, it is not clear how wide is the range of genetic variation in repair capacity among normal individuals. Studies with DNA repair-deficient human syndromes indicate that processes other than mutation and DNA repair must be involved in the development of cancer, and these processes may represent new sources of variation in human response to genotoxic agents.     

汉防己甲素逆转白血病细胞株K562/ADM多药耐药性机制研究

目的 研究汉防己甲素(TTD)对慢性粒细胞白血病急性变白血病细胞株K562／ADM多药耐药(MDR)逆转的机理。方法 采用流式细胞仪检测细胞内化疗药物的浓度及细胞表面P糖蛋白(P-gp)的表达；荧光定量PCR法检测MDR1 mRNA；通过流式细胞仪检测Anexin—V判断凋亡细胞的数量。结果 10μmol/L的TTD处理K562／ADM细胞后，细胞内阿霉素(ADM)的浓度明显提高；K562／ADM细胞MDR1 mRNA／P-gp的表达下降；TTD能增强ADM致细胞凋亡的作用。结论 汉防己甲素的耐药逆转机制除了下调MDR1 mRNA／P-gp的表达引起细胞内抗癌药物的积聚外，增加抗癌药物致细胞凋亡也是耐药逆转的重要原因。．     

Are our donors safe?

Blood is defined as a ’drug’ under the Drugs and Cosmetics Act. The Standard of drugs is laid down in the Indian Pharmacopoeia. The first step towards blood safety is to encourage blood donations, which are voluntary, non-remunerated and obtained from low-risk and regular donors. A regular donor is one who donates blood two to three times a year and continues to donate at least once a year. Over the last 8 years, the Drug Control Authority has been taken up many steps to improve the quality of blood in circulation. As a result, blood centres are now equipped with minimum modern tests for making blood safer. The inspectors are also emphasising the need to employ uniform procedures for donor selection, donor deferral, validation of equipment, and so on. Over the last 5 years, quality control of diagnostic kits prior to their registration and marketing have been streamlined to ensure that blood centres use highly sensitive kits while testing for blood transmissible diseases. Therefore, current methods of donor screening and testing of donated blood have led to a remarkable decrease in the incidence of transfusion-transmitted infection and a blood supply that is very safe. The greatest threat to blood safety is donation by seronegative individuals during the infectious window period when they are undergoing seroconversion and infection cannot be detected by available laboratory tests. Look-backs is the process whereby blood collection facilities attempt to indentify prior recipients of blood donated by individuals who subsequently test positive TTD. This alone can assure safety.     

汉防己甲素抗血吸虫病小鼠肝纤维化实验研究

目的探讨汉防己甲素抗血吸虫病肝纤维化作用。方法采用免疫组化法、VG染色及多媒体病理图文定量分析,观察汉防己甲素治疗前后血吸虫病肝纤维化小鼠肝脏的病理改变及Ⅰ、Ⅲ型胶原蛋白含量的变化,并与未治疗组及生理盐水对照组比较。结果汉防己甲素治疗组肝内Ⅰ、Ⅲ型胶原蛋白的含量明显下降,与生理盐水对照组及未治疗组比较,差异有显著性(P<0.01)。结论汉防己甲素可降低血吸虫病小鼠肝内Ⅰ、Ⅲ型胶原蛋白的含量,从而发挥抗肝纤维化的作用。     

The efferent connections of the nuclei of the descending trigeminal tract in the mallard (Anas platyrhynchos L.)

The efferent and intranuclear connections of the nuclei of the descending trigeminal tract of the mallard have been studied with lesion methods, and by axonal transport techniques following injections of tritiated leucine, and of horseradish peroxidase.The large subnucleus oralis neurons, including those belonging to the nucleus of the ascending glossopharyngeal tract, have proven to be the sole origin of trigeminocerebellar connections. The cerebellar afferents are of the mossy fiber type, and terminate predominantly in lobules V, VI and VII, and possibly, lobule IV. Trigeminocerebellar projections are ipsilateral except for the vermal area.Subnucleus interpolaris is the main source of intratrigeminal fibers that terminate in subnucleus oralis and the ventral part of the main sensory nucleus. These intranuclear connections are bilateral, but the medium-celled caudal part of subnucleus interpolaris in particular contains the majority of bi- and/or contralaterally projecting neurons. Additionally, the small cells in the rostral part of subnucleus interpolaris project ipsilaterally upon the parabrachial region, and upon the lateral reticular formation.Projections upon the parabrachial region furthermore emanate bilaterally from layer I of the rostral subnucleus caudalis. A minor part of layer I neurons sends its axons contralaterally along with those of the dorsal column nuclei toward the thalamic nucleus dorsolateralis posterior. Associated with the medial lemniscus, contralateral termination is also present in the lateral part of the ventral lamella of oliva caudalis, in the marginal zone of nucleus mesencephalicus lateralis, pars dorsalis and immediately surrounding intercollicular grey and, finally, in the nucleus intercalatus thalami. Furthermore, a bilaterally descending projection from subnucleus caudalis upon layers I and II of the rostral cervical cord was observed. Close to their origin subnucleus caudalis neurons project upon the adjoining caudal part of the lateral reticular formation.     

Stereotactic Radiofrequency Ablation for Breast Cancer Liver Metastases

Purpose

To evaluate outcomes in patients with liver metastases from breast cancer treated with stereotactic radiofrequency (RF) ablation.

Systems pharmacology strategies for drug discovery and combination with applications to cardiovascular diseases

Ethnopharmacological relevance

Multi-target therapeutics is a promising paradigm for drug discovery which is expected to produce greater levels of efficacy with fewer adverse effects and toxicity than monotherapies. Medical herbs featuring multi-components and multi-targets may serve as valuable resources for network-based multi-target drug discovery.

Materials and methods

In this study, we report an integrated systems pharmacology platform for drug discovery and combination, with a typical example applied to herbal medicines in the treatment of cardiovascular diseases.

Results

First, a disease-specific drug–target network was constructed and examined at systems level to capture the key disease-relevant biology for discovery of multi-targeted agents. Second, considering an integration of disease complexity and multilevel connectivity, a comprehensive database of literature-reported associations, chemicals and pharmacology for herbal medicines was designed. Third, a large-scale systematic analysis combining pharmacokinetics, chemogenomics, pharmacology and systems biology data through computational methods was performed and validated experimentally, which results in a superior output of information for systematic drug design strategies for complex diseases.

Conclusions

This strategy integrating different types of technologies is expected to help create new opportunities for drug discovery and combination.