抗高血压药物与罹患癌症的风险:324168例参与随机临床试验病人的荟萃分析和试验序贯分析

长期以来,一直存在抗高血压药物是否有致癌作用的争议.自从在年龄>50岁的妇女中使用萝芙碱提取物造成乳腺癌发病率增加的报道后[1],这一争议已持续了30年.Sipahi和同事们最近的研究显示:血管紧张素受体拮抗剂(angiotensin receptor-blockers,ARB)有较高的致癌风险.这一发现再次引发了抗...     

Guidelines for reporting experiments involving animals: the ARRIVE guidelines

British Journal of Pharmacology (BJP) is pleased to publish a new set of guidelines for reporting research involving animals, simultaneously with several other journals; the ‘ARRIVE’ guidelines (Animals in Research: Reporting In Vivo Experiments). This editorial summarizes the background to the guidelines, gives our view of their significance, considers aspects of specific relevance to pharmacology, re-states BJP''s guidelines for authors on animal experiments and indicates our commitment to carrying on discussion of this important topic. We also invite feedback via the British Pharmacological Society website.     

Large normal and reduced penetrance alleles in Huntington disease: instability in families and frequency at the laboratory,at the clinic and in the population

Sequeiros J, Ramos EM, Cerqueira J, Costa MC, Sousa A, Pinto‐Basto J, Alonso I. Large normal and reduced penetrance alleles in Huntington disease: instability in families and frequency at the laboratory, at the clinic and in the population. Large normal (‘intermediate’) alleles may produce de novo expansions in Huntington disease; nevertheless, there is very little evidence about their population prevalence and impact in daily practice, and there are conflicting reports about the extent of their instability. We estimated the frequency of large normal alleles (27–35 CAGs) and of reduced penetrance alleles (36–39 CAGs), as well as the frequency of genotypes carrying them, in (i) a diagnostic laboratory, (ii) a genetic counselling clinic and (iii) the general population. Large normal alleles were present in 6% of a large control sample, 7% of consultands who took pre‐symptomatic testing and 7% of samples in the laboratory. Reduced penetrance alleles were found in 1 of 1772 control chromosomes (0.1% of individuals), 5% of 146 pre‐symptomatic testees and over 2% of 1214 diagnostic samples (350 families). All 16 alleles sized 27–32 CAGs seemed to be transmitted stably; alleles ≥ 36 repeats were unstable in five families. Seven small full penetrance alleles contracted into the reduced penetrance range, but none into the large normal range. Evidence showed that large normal alleles are relatively frequent and that those with reduced penetrance are not a rare event, either at the laboratory or the clinic. This reinforces the need to understand the genomic context of repeat instability in each family and population.     

Persistence of anxiety disorders and concomitant changes in cortisol

In a clinical sample of 116 children and adolescents we studied the relation between the course of an anxiety disorder during treatment and the concomitant changes in cortisol levels. Assessments at baseline, after three months, and at one-year follow-up were performed with the Anxiety Disorders Interview Schedule. When we compared cortisol levels at baseline and one-year follow-up, persistence of the anxiety disorder was associated with both increased daytime cortisol production (F=3.2, p=0.04) and a trend towards a decreased cortisol morning rise (F=2.4, p=0.09). At one-year follow-up daytime cortisol production was lowest in the early remitters (109.7±29.2 h mmol/l), higher in the late remitters (121.0±40.0 h mmol/l) and highest in the non-remitters (131.1±48.9 h mmol/l). Early remitters had the highest cortisol morning rise (1.1±1.5 h mmol/l), followed by the late remitters (0.8±1.8 h mmol/l), the non-remitters had the lowest cortisol morning rise (0.07±1.7 h mmol/l). Persistence of an anxiety disorder may thus lead to changes in HPA-axis functioning, underscoring the importance adequate treatment of anxiety disorders.     

Cytogenetic and molecular delineation of a region of chromosome 7 commonly deleted in malignant myeloid diseases

Loss of a whole chromosome 7 or a deletion of the long arm, del(7q), are recurring abnormalities in malignant myeloid diseases. To determine the location of genes on 7q that are likely to play a role in leukemogenesis, we examined the deleted chromosome 7 homologs in a series of 81 patients with therapy-related or de novo myelodysplastic syndrome or acute myeloid leukemia. Our analysis showed that the deletions were interstitial and that there were two distinct deleted segments of 7q. The majority of patients (65 of 81 [80%]) had proximal breakpoints in bands q11-22 and distal breakpoints in q31-36; the smallest overlapping deleted segment was within q22. The remaining 16 patients had deletions involving the distal q arm with a commonly deleted segment of q32-33. To define the proximal deleted segment at 7q22 at a molecular level, we used fluorescence in situ hybridization with a panel of mapped yeast artificial chromosome (YAC) clones from 7q to examine 15 patients with deletion breakpoints in 7q22. We determined that the smallest overlapping deleted segment is contained in a well- defined YAC contig that spans 2 to 3 Mb. These studies delineate the region of 7q that must be searched to isolate a putative myeloid leukemia suppressor gene, and provide the necessary cloned DNA for more detailed physical mapping and gene isolation.