Antigen presentation by macrophages is enhanced by the uptake of necrotic, but not apoptotic, cells

The aim of this study was to determine whether phagocytosis of necrotic or apoptotic cells affects antigen presentation by murine bone marrow-derived macrophages. After uptake of necrotic neutrophils, macrophages were able to stimulate significantly higher T cell proliferation in vitro against both the recall antigen albumin and the mitogen concanavalin A. No such effect was seen following phagocytosis of apoptotic neutrophils. Flow cytometry revealed that, within 4h of ingestion, macrophages that had taken up the necrotic cells expressed higher levels of CD40 than those that had phagocytosed apoptotic cells. Macrophage cultures pulsed with apoptotic, but not necrotic, neutrophils contained higher levels of transforming growth factor beta1, but lower concentrations of tumour necrosis factor alpha, compared to untreated controls. Our interpretation of these results is that macrophages that have taken up necrotic neutrophils co-stimulate T cells with greater efficiency due to rapid CD40 up-regulation, whereas those that have ingested apoptotic cells are not only ineffective in co-stimulation, but also secrete inhibitory cytokine.     

Effect of cyclic AMP on histamine release induced by compound 48/80.

Bu2 cAMP(N6, O2'-dibutyryl adenosine-3',5'-cyclic monophosphate) inhibited the response of rat peritoneal mast cells to compound 48/80 in the presence of calcium ions. In the absence of calcium, the nucleotide partially prevented the desensitization induced by chelating agents. The response of cells, allowed to accumulate Bu2 cAMP in the presence of calcium (to avoid depletion of intracellular stores of the ion) and then challenged in the absence of extracellular calcium, was also inhibited. These results are discussed in terms of the postulated effects of Bu2 cAMP on the calcium-gatubg mechanism operative in histamine secretion.     

Leucocyte Migration Test and Hypersensitivity to Glafenin

The leucocyte migration test (LMT) was performed on 20 patients with an intolerance to glafenin--a non-narcotic analgesic drug. LMT was found to be positive in 50% of the subjects with intolerance, a highly significant percentage as compared with the control groups. HSA-glafenin was found to be the most appropriate method for presenting the antigen, but glafenin and its hydroxylated metabolites were only found to induce a migration inhibition in the subjects intolerant to glafenin.     

Astrocyte glutamate receptor activation promotes inositol phospholipid turnover and calcium flux

Astrocyte-enriched cultures prepared from the neonatal rat cortex were prelabelled with either [3H]myoinositol or 45Ca2+ and then exposed to various excitatory amino acids. This resulted in an increase in both the breakdown of membrane inositol phospholipids and Ca2+ flux with the following rank order of efficacy: quisqualate greater than or equal to glutamate (Glu) greater than kainate much greater than N-methyl-D-aspartate. Experiments performed with the Ca2+ ionophore A23187 and in the absence of medium Ca2+ suggested that Glu-evoked 45Ca2+ efflux was primarily the result of an increased influx of extracellular Ca2+. However, Glu-stimulated inositol lipid metabolism was found to be only partially dependent on extracellular Ca2+. The quisqualate-preferring receptor antagonist gamma-glutamylaminomethylsulphonic acid was found to be effective in reversing both Glu-evoked inositol lipid breakdown and Ca2+ flux. The results presented are suggestive of some form of interaction between Glu receptors coupled to inositol lipid turnover and Ca2+ channel opening in astrocytes.     

Knowledge mobilization tool to promote,protect, and support breastfeeding during COVID-19

SettingThis knowledge mobilization project was conceptualized to increase awareness among breastfeeding mothers and the general public on safe infant feeding practices during the COVID-19 pandemic by addressing myths and misconceptions associated with breastfeeding practices, guiding breastfeeding mothers to make informed decisions around child feeding practices, and offering meaningful guidance in simple language through a short online animated video.InterventionThis project was undertaken in four phases. During phase 1, an informal discussion was held with the breastfeeding mothers, service providers, and community partner in identifying issues surrounding lactation counselling facilities during the COVID-19 pandemic. During phase 2, recommendations from 23 organizations with regard to breastfeeding during COVID-19 were reviewed and analyzed. During phase 3, using evidence from reliable sources, a 5-minute animated e-resource on breastfeeding during COVID-19 was conceptualized and developed. During phase 4, the e-resource was disseminated to the breastfeeding mothers, general public, post-secondary institutions, and organizations providing services to breastfeeding mothers in Canada.OutcomesThis evidence-based e-resource facilitated addressing misconceptions around breastfeeding during COVID-19 and raising public awareness on safe infant feeding practices during this pandemic. Overall, the video was described as an informative, user-friendly, useful, and easily accessible resource by breastfeeding mothers who were in self-isolation with little access to healthcare services during the pandemic.ImplicationsThis project highlighted the importance of patient engagement and collaboration with the community partner in protecting breastfeeding during the COVID-19 pandemic. It further illustrated how informational e-resources can protect breastfeeding in situations where breastfeeding mothers’ access to healthcare services is compromised.     

Multifocal intraocular lenses

It has been 10 years since I implanted the first multifocal intraocular lens (IOL). Unfortunately, there has been a gradual lessening of commitment to this modality by the ophthalmic community. The most important single factor for this lack of interest despite the more than adequate available clinical data is the repeated moving of "goal posts" by the American FDA when a multifocal lens style nears premarket approval. The refractive multifocal lens styles of iolab (Claremont, CA), Stortz Ophthalmics (St. Louis, MO), Domilens (Lyon, France), and Amo with the diffractive multifocals of 3M (St. Louis, MO), and Pharmacia (Kalamazoo, MI) and their recent modifications are reviewed. Reports show that they generally give excellent visual results depending on whether a near or distance dominant lens is indicated. The foldable Amo Array SA40N provides a good distance dominant foldable lens for the surgeon performing small incisions and has a small but dedicated surgical following. Loss of contrast sensitivity at low-light levels remains a source of concern in certain professions and with certain lifestyles, and a report suggesting that many monofocal and multifocal patients do not achieve the standards set for night driving by the German Ophthalmic Society warrants further consideration. Development of a new accommodative IOL for small incision surgery is the only really new concept, and it will be interesting to see the results of independent reports. Spectacle dependence is considerably reduced with all the current multifocals when compared to monofocals, and for patients there are ample multifocal lens styles from which to choose. It is the author's opinion that more than 60% of the cataract population is currently suitable for multifocals if small incision surgery is performed. More multifocals would be used if price disparity with monofocals was reduced.