Fluorescent ligand binding reveals heterogeneous distribution of adrenoceptors and ‘cannabinoid-like’ receptors in small arteries

Background and purpose:

Pharmacological analysis of synergism or functional antagonism between different receptors commonly assumes that interacting receptors are located in the same cells. We have now investigated the distribution of α-adrenoceptors, β-adrenoceptors and cannabinoid-like (GPR55) receptors in the mouse arteries.

Experimental approach:

Fluorescence intensity from vascular tissue incubated with fluorescent ligands (α₁-adrenoceptor ligand, BODIPY-FL-prazosin, QAPB; β-adrenoceptor ligand, TMR-{"type":"entrez-protein","attrs":{"text":"CGP12177","term_id":"877152897","term_text":"CGP12177"}}CGP12177; fluorescent angiotensin II; a novel diarylpyrazole cannabinoid ligand (Tocrifluor 1117, T1117) was measured with confocal microscopy. Small mesenteric and tail arteries of wild-type and α_1B/D-adrenoceptor-KO mice were used.

Key results:

T1117, a fluorescent form of the cannabinoid CB₁ receptor antagonist AM251, was a ligand for GPR55, with low affinity for CB₁ receptors. In mesenteric arterial smooth muscle cells, α_1A-adrenoceptors were predominantly located in different cells from those with β-adrenoceptors, angiotensin receptors or cannabinoid-like (GPR55) receptors. Cells with β-adrenoceptors predominated at arterial branches. Endothelial cells expressed β-adrenoceptors, α-adrenoceptors and cannabinoid-like receptors. Only endothelial α-adrenoceptors appeared in clusters. Adventitia was a rich source of G protein-coupled receptors (GPCRs), particularly fibroblasts and nerve tracts, where Schwann cells bound α-adrenoceptor, β-adrenoceptor and CB-receptor ligands, with a mix of separate receptor locations and co-localization.

Conclusions and implications:

Within each cell type, each GPCR had a distinctive heterogeneous distribution with limited co-localization, providing a guide to the possibilities for functional synergism, and suggesting a new paradigm for synergism in which interactions may be either between cells or involve converging intracellular signalling processes.This article is part of a themed section on Imaging in Pharmacology. To view the editorial for this themed section visit http://dx.doi.org/10.1111/j.1476-5381.2010.00685.x     

Review concludes that specific recommendations are needed to harmonise the provision of fresh mother's milk to their preterm infants

Aim

There are no specific recommendations for using a mother's fresh milk for her preterm infant. We reviewed the available evidence on its collection, storage and administration.

Methods

The working group of the French Neonatal Society on fresh human milk use in preterm infants searched the MEDLINE database and Cochrane Library up to June 2017 for papers published in English or French. They specifically analysed 282 papers providing information on prospective, retrospective and clinical studies and examined guidelines from various countries.

Results

The review concluded that fresh mother's own milk should be favoured in accordance with the latest recommendations. However, it must be carried out under stringent conditions so that the expected benefits are not offset by risks related to different practices. The working group has summarised the best conditions for feeding preterm infants with human milk, balancing high nutritional and immunological quality with adequate virological and bacteriological safety. Professionals must provide parents with the necessary conditions to establish breastfeeding, together with specific and strong support.

Conclusion

Based on their review, the working group has made specific recommendations for using fresh mother's own milk under careful conditions, so that the expected benefits are not offset by risks related to practices.     

多巴胺肽类衍生物的合成及其对心功能的影响

将氨基酸或小肽引入多巴胺分子中,共合成了十八个具有不同立体构型和亲脂性的氨基酸多巴胺肽。在麻醉狗上药理初筛表明,多巴胺分子中引入L型氨基酸非常显著地增加心肌收缩力和动脉压,而引入D型氨基酸或N-甲基氨基酸后,则生理活性显著减弱。当多巴胺分子中引入亲脂性的氨基酸后,能明显增加心肌收缩力和血压,同时能明显延长作用时间。     

Growth of the fetal kidney. Ultrasonographic measurement of the ratio of average kidney diameter to biparietal diameter

Kidney size was studied ultrasonographically in 101 normal fetuses. A ratio of average kidney diameter to biparietal diameter was established and found to be constant across gestation. Three fetuses with known urinary tract pathology were then studied and were found to have ratios significantly different from normal ones.     

Response to subdermal implantation of textured microimplants in humans

In lieu of the problems involved with the use of foreign substances such as ivory, paraffin, liquid silicone, and collagen, a new subcutaneous injectable device has been developed. This material—Bioplastique—has been developed in an attempt to overcome the shortcomings of previous augmentation materials, most notably absorption, migration, and immunologic rejection. This article presents a longitudinal study of the use of this new microimplant.     

Doing randomized controlled trials in a developing country: some practical realities

BACKGROUND: Formal randomized controlled trial results are often reported.The difficulties of doing such trials are not. Developing countriesrepresent a new field in which trials can be undertaken. Inthis context even less is known about the practicalities involved. METHOD AND RESULTS: A randomized, double-blind, parallel study took significantlylonger than expected to complete and subject recruitment andparticipation fell short of expectations. Different recruitmentstrategies were used and these performed differently in termsof enrolling trialists. Subjects most frequently left the trialin its early stages. CONCLUSIONS: Possible explanations for these findings include the demographyof the country, cultural factors, and the existence of an establisheddoctor-patient relationship. Keywords. Developing countries, drug treatment hypertension, randomized controlled trials, United Arab Emirates.