Double deletion of orexigenic neuropeptide Y and dynorphin results in paradoxical obesity in mice

Objective

Orexigenic neuropeptide Y (NPY) and dynorphin (DYN) regulate energy homeostasis. Single NPY or dynorphin deletion reduces food intake or increases fat loss. Future developments of obesity therapeutics involve targeting multiple pathways. We hypothesised that NPY and dynorphin regulate energy homeostasis independently, thus double NPY and dynorphin ablation would result in greater weight and/or fat loss than the absence of NPY or dynorphin alone.

Design and methods

We generated single and double NPY and dynorphin knockout mice (NPYΔ, DYNΔ, NPYDYNΔ) and compared body weight, adiposity, feeding behaviour, glucose homeostasis and brown adipose tissue uncoupling protein-1 (UCP-1) expression to wildtype counterparts.

Results

Body weight and adiposity were significantly increased in NPYDYNΔ, but not in NPYΔ or DYNΔ. This was not due to increased food intake or altered UCP-1 expression, which were not significantly altered in double knockouts. NPYDYNΔ mice demonstrated increased body weight loss after a 24-h fast, with no effect on serum glucose levels after glucose injection.

Conclusions

Contrary to the predicted phenotype delineated from single knockouts, double NPY and dynorphin deletion resulted in heavier mice, with increased adiposity, despite no significant changes in food intake or UCP-1 activity. This indicates that combining long-term opioid antagonism with blockade of NPY-ergic systems may not produce anti-obesity effects.     

B cells as a critical node in the microbiota–host immune system network

Mutualism with our intestinal microbiota is a prerequisite for healthy existence. This requires physical separation of the majority of the microbiota from the host (by secreted antimicrobials, mucus, and the intestinal epithelium) and active immune control of the low numbers of microbes that overcome these physical and chemical barriers, even in healthy individuals. In this review, we address how B-cell responses to members of the intestinal microbiota form a robust network with mucus, epithelial integrity, follicular helper T cells, innate immunity, and gut-associated lymphoid tissues to maintain host–microbiota mutualism.     

Increased myocardial methionine‐enkephalin with reduced arterial oxygenation in congenital heart disease

Background: Cardiac opioid peptides have been identified to exert important adaptive metabolic signalling for cardioprotection against ischaemia or hypoxia‐related injury. Aims: To determine myocardial methionine‐enkephalin content in children with hypoxemic congenital heart defects and to correlate myocardial content of methionine‐enkephalin with the extent of arterial oxygen desaturation. Methods: Children (n= 20, median age of 16 months), undergoing cardiac surgical repair (tetralogy of Fallot, 17/20), were included in this study. Arterial oxygen saturation was measured on admission. Myocardial samples obtained during surgery were assayed via radioimmunochemistry for methionine‐enkephalin content. Results: Greater methionine‐enkephalin content was measured in the right ventricles of the patients suffering from recent cyanotic spells compared with those with no recent spells (cyanotic spells: 2418 ± 844 pg/g wet weight tissue, n= 6; no spells: 1175 ± 189 pg/g wet weight tissue, n= 14, P= 0.04). An inverse correlation was evident between the arterial oxygen saturation and myocardial methionine‐enkephalin content. Conclusion: Myocardial methionine‐enkephalin levels increase with the severity of hypoxic stress in congenital cardiac disease and may play an important adaptive role in countering adrenergic over‐activity and related excess demand on myocardial metabolic capacity.     

Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast cancer

Background After neoadjuvant chemotherapy, women with locally advanced breast cancer (LABC) undergo a modified radical mastectomy or lumpectomy with axillary lymph node dissection (ALND) and radiotherapy. Sentinel lymphadenectomy (SL) is accepted for axillary evaluation in early breast cancer. We assessed the feasibility and predictive value of SL after neoadjuvant chemotherapy. Methods Eligible women received neoadjuvant therapy for LABC and were scheduled to undergo a definitive surgical procedure. Vital blue dye SL was attempted followed by level I and II axillary dissection. Results SL was successful in 29 of 34 patients (detection rate, 85%). Thirteen patients (45%) had positive nodes, and eight (28%) had negative nodes on both SL and ALND. In five patients (17%), the sentinel node was the only positive node identified. Overall, there was a 90% concordance between SL and ALND. The false-negative rate and negative predictive value were 14% and 73%, respectively. Among the subgroup without inflammatory cancer, the detection and concordance rates were 89% and 96%, respectively. The false-negative rate was 6%, and the negative predictive value was 88%. Conclusions SL after neoadjuvant chemotherapy may reliably predict axillary staging except in inflammatory breast cancer. Further studies are required to assess the utility of SL as the only mode of axillary evaluation in these women.     

A pilot study of the SNOT 22 score in adults with no sinonasal disease

Objective: To determine the SNOT 22 score in a normal population. Study design: Analysis of SNOT 22 scores participants with no sinonasal disease. Setting: Bath, UK. Participants: 116 participants from a local hospital and tennis club. Results: Results were obtained from 54 men and 62 women with a mean age of 40 (range 19–75). SNOT score ranged from 0–50 with a mean score of 9.3 (95% confidence interval range of 7.5–11.1). The modal score was 0 and the median score 7 (95% confidence interval range of 5–8). Conclusion: Due to the scewed nature of the data, the median score (7) is taken as the normal SNOT 22 score. We recommend that in an clincial situation a SNOT 22 score of 7 be used a a guide for “normal”, and that care should be taken when suggesting treatment on patients with a score below this level.     

广州市12~13岁儿童牙龈炎与恒牙龋患病关系的调查分析

【目的】 探讨儿童牙龈炎与恒牙龋的相关关系,为儿童牙龈炎防治工作提供理论依据。 【方法】 采用多阶段分层整群随机抽样的方法共调查广州市12~13岁儿童1 115人。检查方法和标准参考1997年WHO推荐的《口腔健康调查基本方法》,牙龈炎检查六颗指数牙,龋病检查全口恒牙,分别采用牙龈指数(GI)和DMFT记录检查结果。Logistic回归分析儿童牙龈炎与恒牙龋病的关系。 【结果】 广州市12~13岁儿童牙龈炎患病率72.65%,中、重度牙龈炎患病率分别为28.16%和5.83%。恒牙龋患病率为25.83%,其中未充填龋占龋齿的73.73%。Logistic回归分析显示未充填龋是广州市12~13岁儿童牙龈炎患病的危险因素。 【结论】 广州市12~13岁儿童牙龈炎患病率较高,有未充填龋存在的儿童是广州市儿童牙龈炎重点防治人群。