Prostaglandin signaling suppresses beneficial microglial function in Alzheimer’s disease models

Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer’s disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE₂) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aβ peptides and determined that microglia-specific deletion of the gene encoding the PGE₂ receptor EP2 restores microglial chemotaxis and Aβ clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE₂/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD.     

Blood histamine levels in cotton-dust exposed workers in a textile mill of Ahmedabad

Blood histamine levels were measured by the bioassay of histamine (on an isolated strip of guinea pig ileum) in workers exposed to cotton dust in a textile mill in Ahmedabad. Byssinotic subjects showed very high levels of blood histamine as compared to nonbyssinotic and control subjects. The blood histamine levels were not well correlated to the dust concentrations or duration of exposure but rather to the day of the week (ie, first, second, third, etc., after weekend break) on which the samples were collected. The blood histamine levels were high on the first day of the work week, when byssinotics complained most of their symptoms.     

Vasopeptidase inhibition with omapatrilat improves cardiac geometry and survival in cardiomyopathic hamsters more than does ACE inhibition with captopril

Vasopeptidase inhibitors are single molecules that inhibit neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) simultaneously. Omapatrilat, the first in this new class of cardiovascular agents, potentiates vasodilatory and cardioprotective peptides and represses angiotensin II. This study compared the effects of omapatrilat with those of a pure ACE inhibitor on cardiac geometry and survival in animals with heart failure. BIO TO-2 cardiomyopathic hamsters (CMHs) in the early stages of dilated heart failure were treated with vehicle or maximal ACE inhibitory doses of captopril (750 micromol/kg/day) or omapatrilat (200 micromol/kg/day). Prolonged vasopeptidase inhibition increased median survival time after the start of treatment by 99 and 31% compared with vehicle and captopril, respectively (median survival times: 146, 221, and 290 days with vehicle, captopril, and omapatrilat, respectively; p < 0.001 for all comparisons). In similar CMHs, captopril or omapatrilat administered for 2 months significantly (p < 0.05) decreased heart weight, pulmonary congestion (lung weight), and left ventricular (LV) chamber volume compared with vehicle. Omapatrilat significantly increased LV mass-to-volume ratio compared with vehicle and captopril. Omapatrilat, but not captopril, significantly increased urinary atrial natriuretic peptide excretion, indicating NEP inhibition. Thus vasopeptidase inhibition with omapatrilat was more effective than ACE inhibition with captopril in preventing changes in LV geometry and premature mortality in hamsters with dilated heart failure.     

Effectiveness and future implications of COVID-19-related risk stratification for managing retinopathy of prematurity: The Indian twin cities retinopathy of prematurity study report number 10

Purpose:To evaluate the effectiveness and future implications of COVID-related risk stratification for managing retinopathy of prematurity (ROP).Methods:A prospective study was conducted at a tertiary eye care center from the beginning of the lockdown in India from 23 March 2020 till the end of the first phase of lockdown on 29 May 2020. We evaluated 200 prematurely born infants (< 34 weeks of gestational age) using the new safety guideline protocols for low-risk babies developed in conjunction with the Indian ROP Society for care during the COVID-19 pandemic. Low risk included babies born at more than 30 weeks of gestational age, post menstrual age 34 weeks or above at presentation, more than 1000 grams of birth weight, and stable systemically with good weight gain.Results:New guidelines were implemented in 106 (53%) infants who were low risk while 94 (47%) infants with high risk were followed up as per the old guidelines. Out of the 106 infants (212 eyes) managed by the new guidelines, good outcome (group 1) was seen in 102 (96.2%) infants. Twenty-seven of the 102 infants had some form of ROP and 5 of these infants needed treatment. None of the low-risk babies with no detachment at presentation managed by new guidelines required surgery later (group 2). Two (1.9%) infants came with retinal detachment at presentation and underwent successful surgery (group 3) and two infants (1.9%) were lost to follow up.Conclusion:New risk stratification during the COVID-19 pandemic was an efficient and safe strategy in managing low-risk ROP babies.