Reactive microglia and macrophages are prevalent in damaged retinas. Accordingly, we investigate how the activation or ablation of microglia/macrophages influences the survival of neurons in the ...chick retina in vivo. We applied intraocular injections of interleukin 6 (IL6) to stimulate the reactivity of microglia/macrophages and clodronate‐liposomes to ablate microglia/macrophages. Activation of the microglia/macrophages with IL6 delays the death of retinal neurons from N‐methyl‐D‐aspartate (NMDA) ‐induced excitotoxicity. In addition, activation of microglia/macrophages combined with colchicine‐mediated retinal damage diminished the survival of ganglion cells. Application of IL6 after an excitotoxic insult greatly exacerbates the damage, and causes widespread retinal detachments and folds, accompanied by accumulation of microglia/macrophages in the subretinal space. Damage‐induced retinal folds and detachments were significantly reduced by the ablation of microglia/macrophages. We conclude that microglial reactivity is detrimental to the survival of ganglion cells in colchicine‐damaged retinas and detrimental to the survival of photoreceptors in retinal folds. In addition, we conclude that IL6‐treatment transiently protects amacrine and bipolar cells against an excitotoxic insult. We propose that suppressing reactivity of microglia/macrophages may be an effective means to lessen the damage and vision loss resulting from damage, in particular during retinal detachment injuries. GLIA 2015;63:313–327
Main Points
Reactive microglia/macrophages accumulate in the subretinal space of detached/folded regions of retina.
Activation of microglial reactivity with a pro-inflammatory cytokine exacerbates retinal folds and detachments
Ablation of reactive microglia/macrophages in the retina completely prevents the formation of folds and detachments
The mammalian heart is responsible for not only pumping blood throughout the body but also adjusting this pumping activity quickly depending upon sudden changes in the metabolic demands of the body. ...For the most part, the human heart is capable of performing its duties without complications; however, throughout many decades of use, at some point this system encounters problems. Research into the heart's activities during healthy states and during adverse impacts that occur in disease states is necessary in order to strategize novel treatment options to ultimately prolong and improve patients' lives. Animal models are an important aspect of cardiac research where a variety of cardiac processes and therapeutic targets can be studied. However, there are differences between the heart of a human being and an animal and depending on the specific animal, these differences can become more pronounced and in certain cases limiting. There is no ideal animal model available for cardiac research, the use of each animal model is accompanied with its own set of advantages and disadvantages. In this review, we will discuss these advantages and disadvantages of commonly used laboratory animals including mouse, rat, rabbit, canine, swine, and sheep. Since the goal of cardiac research is to enhance our understanding of human health and disease and help improve clinical outcomes, we will also discuss the role of human cardiac tissue in cardiac research. This review will focus on the cardiac ventricular contractile and relaxation kinetics of humans and animal models in order to illustrate these differences.
Background: In the absence of a gold-standard diagnostic modality for cellulitis, sterile inflammatory disorders may be misdiagnosed as cellulitis. Objective: To determine the utility of skin biopsy ...and tissue culture for the diagnosis and management of patients admitted with a diagnosis of presumed cellulitis. Design: Pilot single-blind parallel group randomized controlled clinical trial in 56 patients with a primary diagnosis of presumed cellulitis. In the intervention group only, skin biopsy and tissue culture results were made available to the primary care team to guide diagnosis and management. Length of hospital stay and antibiotic use were evaluated as outcome measures. Results: Length of stay showed the greatest opportunity for further study as a primary outcome (intervention: 4, IQR (2–6) vs. control: 5 IQR (3–8) days;
p
= 0.124). Limitations: The COVID-19 pandemic placed limitations on participant enrollment and study duration; in addition, data was collected from a single medical center. Conclusion: This study demonstrates that length of stay and anti-pseudomonal antibiotic de-escalation are endpoints that may be influenced by biopsy and tissue culture results in presumed cellulitis patients; these outcomes warrant further study.
Heart failure (HF) is associated with highly significant morbidity, mortality, and health care costs. Despite the significant advances in therapies and prevention, HF remains associated with poor ...clinical outcomes. Understanding the contractile force and kinetic changes at the level of cardiac muscle during end-stage HF in consideration of underlying etiology would be beneficial in developing targeted therapies that can help improve cardiac performance.
Investigate the impact of the primary etiology of HF (ischemic or non-ischemic) on left ventricular (LV) human myocardium force and kinetics of contraction and relaxation under near-physiological conditions.
Contractile and kinetic parameters were assessed in LV intact trabeculae isolated from control non-failing (NF; n = 58) and end-stage failing ischemic (FI; n = 16) and non-ischemic (FNI; n = 38) human myocardium under baseline conditions, length-dependent activation, frequency-dependent activation, and response to the β-adrenergic stimulation. At baseline, there were no significant differences in contractile force between the three groups; however, kinetics were impaired in failing myocardium with significant slowing down of relaxation kinetics in FNI compared to NF myocardium. Length-dependent activation was preserved and virtually identical in all groups. Frequency-dependent activation was clearly seen in NF myocardium (positive force frequency relationship FFR), while significantly impaired in both FI and FNI myocardium (negative FFR). Likewise, β-adrenergic regulation of contraction was significantly impaired in both HF groups.
End-stage failing myocardium exhibited impaired kinetics under baseline conditions as well as with the three contractile regulatory mechanisms. The pattern of these kinetic impairments in relation to NF myocardium was mainly impacted by etiology with a marked slowing down of kinetics in FNI myocardium. These findings suggest that not only force development, but also kinetics should be considered as a therapeutic target for improving cardiac performance and thus treatment of HF.
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•Impaired baseline contraction/relaxation kinetics is dependent on etiology of HF.•Length-dependent activation of force development is not impaired in HF myocardium.•Kinetics of HF myocardium do accelerate with heart rate similar to NF myocardium.•Isoproterenol has different inotropic action between NF and HF myocardium.•Improving impaired contractile kinetics may be key in combating human end-stage HF.
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