Distribution of bound tritium from 3H-diethylnitrosamine in rat tissues

The concentration of bound ³H from diethyl-(mono-2-³H)-nitrosamine was determined in five different rat tissues as a function of time after single and repeated oral doses of the labelled carcinogen. The recorded curves can be described as two-component kinetics. Whereas the first component decreased with a half-life of about 3–6 h, the corresponding value for the second component was approximately 90 h. Two hundred and forty hours after a single ³H-DEN dose, the highest relative concentration of bound ³H was recorded in the liver (1.00), followed by kidney (0.74), spleen (0.40), small intestine (0.18), and lung (0.14). The capacity of the liver to metabolically activate DEN, as reflected by the tissue-specific accumulation of bound ³H after repeated ³H-DEN doses, was not impaired at an advanced stage of hepatocarcinogenesis by DEN.     

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.     

Treatment adherence, competence, and outcome in individual and family therapy for adolescent behavior problems

This study examined the impact of treatment adherence and therapist competence on treatment outcome in a controlled trial of individual cognitive-behavioral therapy (CBT) and multidimensional family therapy (MDFT) for adolescent substance use and related behavior problems. Participants included 136 adolescents (62 CBT, 74 MDFT) assessed at intake, discharge, and 6-month follow-up. Observational ratings of adherence and competence were collected on early and later phases of treatment (192 CBT sessions, 245 MDFT sessions) by using a contextual measure of treatment fidelity. Adherence and competence effects were tested after controlling for therapeutic alliance. In CBT only, stronger adherence predicted greater declines in drug use (linear effect). In CBT and MDFT, (a) stronger adherence predicted greater reductions in externalizing behaviors (linear effect) and (b) intermediate levels of adherence predicted the largest declines in internalizing behaviors, with high and low adherence predicting smaller improvements (curvilinear effect). Therapist competence did not predict outcome and did not moderate adherence-outcome relations; however, competence findings are tentative due to relatively low interrater reliability for the competence ratings. Clinical and research implications for attending to both linear and curvilinear adherence effects in manualized treatments for behavior disorders are discussed.