Neuroinflammation contributes to neuronal degeneration in Parkinson's disease (PD). However, how brain inflammatory factors mediate the progression of neurodegeneration is still poorly understood. ...Experimental models of PD have shed light on the understanding of this phenomenon, but the exploration of inflammation-driven models is necessary to better characterize this aspect of the disorder. The use of lipopolysaccharide (LPS) to induce a neuroinflammation-mediated neuronal loss is useful to induce reliable elimination of dopaminergic neurons. Nevertheless, how this model parallels the PD-like neuroinflammation is uncertain. In the present work, we used the direct LPS injection as a model inductor to eliminate dopaminergic neurons of the substantia nigra pars compacta (SNpc) in rats and reevaluated the inflammatory reaction. High-resolution 3D histological examination revealed that, although LPS induced a reliable elimination of SNpc dopaminergic neurons, it also generated a massive inflammatory response. This inflammation-mediated injury was characterized by corralling, a damaged parenchyma occupied by a vast population of lesion-associated microglia and macrophages (LAMMs) undertaking wound compaction and scar formation, surrounded by highly reactive astrocytes. LAMMs tiled the entire lesion and engaged in long-standing phagocytic activity to resolve the injury. Additionally, modeling LPS inflammation in a cell culture system helped to understand the role of phagocytosis and cytotoxicity in the initial phases of dopaminergic degeneration and indicated that LAMM-mediated toxicity and phagocytosis coexist during LPS-mediated dopaminergic elimination. However, this type of severe inflammatory-mediated injury, and subsequent resolution appear to be different from the ageing-related PD scenario where the architectural structure of the parenchyma is mostly preserved. Thus, the necessity to explore new experimental models to properly mimic the inflammatory compound observed in PD degeneration.
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•LPS-induced mesencephalic injury causes corralling of microglia/macrophages•LPS-mediated lesion in SNpc triggers microglia/macrophages tiling and honeycomb structures•Microglia/macrophages tiling contributes to promote interactions with remnant dopaminergic neurons and debris•Corralled lesion shows high phagocytic capacity of dopaminergic remains
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Metacaspases and paracaspases are proteases that were first identified as containing a caspase-like structural fold (
Uren et al., 2000
). Like caspases, meta- and paracaspases are multifunctional ...proteins regulating diverse biological phenomena, such as aging, immunity, proteostasis and programmed cell death. The broad phylogenetic distribution of meta- and paracaspases across all kingdoms of life and large variation of their biochemical and structural features complicate classification and annotation of the rapidly growing number of identified homologs. Establishment of an adequate classification and unified nomenclature of meta- and paracaspases is especially important to avoid frequent confusion of these proteases with caspases - a tenacious misnomer that unfortunately does not appear to decline with time. This letter represents a consensus opinion of researchers studying different aspects of caspases, meta- and paracaspases in various organisms, ranging from microbes to plants and animals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although the primary physiological abnormality in chronic obstructive pulmonary disease (COPD) is airway obstruction, extrapulmonary manifestations of COPD also contribute to the risk of death. The ...authors of this study devised a novel index based on body-mass index, the forced expiratory volume in one second, the distance walked in six minutes, and the patient's perceived level of dyspnea.
Body-mass index, forced expiratory volume, distance walked, and level of dyspnea can predict the risk of death.
Chronic obstructive pulmonary disease (COPD), a common disease characterized by a poorly reversible limitation in airflow,
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is predicted to be the third most frequent cause of death in the world by 2020.
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The risk of death in patients with COPD is often graded with the use of a single physiological variable, the forced expiratory volume in one second (FEV
1
).
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,
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However, other risk factors, such as the presence of hypoxemia or hypercapnia,
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a short distance walked in a fixed time,
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a high degree of functional breathlessness,
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and a low body-mass index (the weight in kilograms divided . . .
Systolic hypertension is associated with cognitive decline in the elderly. Altered blood pressure (BP) variability is a possible mechanism of reduced cognitive performance in elderly hypertensives. ...We hypothesized that altered beat-to-beat systolic BP variability is associated with reduced global cognitive performance in elderly hypertensive subjects. In exploratory analyses, we also studied the correlation between diverse discrete cognitive domains and indices of systolic BP and heart rate variability. Disproving our initial hypothesis, we have shown that hypertension and low education, but not indices of systolic BP and heart rate variability, were independent predictors of lower global cognitive performance. However, exploratory analyses showed that the systolic BP variability in semi-upright position was an independent predictor of matrix reasoning (B = 0.08 ± .03, P-value = 0.005), whereas heart rate variability in semi-upright position was an independent predictor of the executive function score (B = -6.36 ± 2.55, P-value = 0.02). We conclude that myogenic vascular and sympathetic modulation of systolic BP do not contribute to reduced global cognitive performance in treated hypertensive subjects. Nevertheless, our results suggest that both systolic BP and heart rate variability might be associated with modulation of frontal lobe cognitive domains, such as executive function and matrix reasoning.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The importance of early and aggressive initiation of secondary prevention strategies for patients with both coronary artery disease (CAD) and cerebrovascular disease (CVD) is emphasized by multiple ...guidelines. However, limited information is available on cardiovascular protection and stroke prevention in an outpatient setting from community-based populations. We sought to evaluate and compare differences in treatment patterns and the attainment of current guideline-recommended targets in unselected high-risk ambulatory patients with CAD, CVD, or both.
This multicenter, prospective, cohort study was conducted from December 2001 to December 2004 among ambulatory patients in a primary care setting. The prospective Vascular Protection and Guidelines-Oriented Approach to Lipid-Lowering Registries recruited 4933 outpatients with established CAD, CVD, or both. All patients had a complete fasting lipid profile measured within 6 months before enrollment. The primary outcome measure was the achievement of blood pressure (BP) <140/90 mm Hg (or <130/80 mm Hg for patients with diabetes) and LDL cholesterol <2.5 mmol/L (<97 mg/dL) according to the Canadian guidelines in place at that time (similar to the National Cholesterol Education Program's value of 100 mg/dL). Secondary outcomes include use of antithrombotic, antihypertensive, and lipid-modifying therapies.
Of the 4933 patients, 3817 (77%) had CAD only; 647 (13%) had CVD only; and 469 (10%) had both CAD and CVD. Mean+/-SD age was 67+/-10 years, and 3466 (71%) were male. Mean systolic and diastolic BPs were 130+/-16 and 75+/-9 mm Hg, respectively. Minor but significant differences were observed on baseline BP, total cholesterol, and LDL cholesterol measurements among the 3 groups. Overall, 83% of patients were taking a statin and 93% were receiving antithrombotic therapy (antiplatelet and/or anticoagulant agents). Compared with patients with CAD, those with CVD only were less likely to achieve the recommended BP (45.3% vs 57.3%, respectively; P<0.001) and lipid (19.4% vs 30.5%, respectively; P<0.001) targets. Among patients with CVD only, women were less likely to achieve the recommended BP and lipid targets compared with their male counterparts (for LDL cholesterol <2.5 mmol/L, 18.7% vs 23.8%, respectively; P=0.048). In multivariable analysis, patients with CVD alone were less likely to achieve treatment success (BP or lipid targets) after adjusting for age, sex, diabetes, and use of pharmacologic therapy.
Despite the proven benefits of available antihypertensive and lipid-lowering therapies, current management of hypertension and dyslipidemia continues to be suboptimal. A considerable proportion of patients failed to achieve guideline-recommended targets, and this apparent treatment gap was more pronounced among patients with CVD and women. Quality improvement strategies should target these patient subgroups.
The 6-min walk distance (6MWD) predicted values have been derived from small cohorts mostly from single countries. The aim of the present study was to investigate differences between countries and ...identify new reference values to improve 6MWD interpretation. We studied 444 subjects (238 males) from seven countries (10 centres) ranging 40-80 yrs of age. We measured 6MWD, height, weight, spirometry, heart rate (HR), maximum HR (HR(max)) during the 6-min walk test/the predicted maximum HR (HR(max) % pred), Borg dyspnoea score and oxygen saturation. The mean ± sd 6MWD was 571 ± 90 m (range 380-782 m). Males walked 30 m more than females (p < 0.001). A multiple regression model for the 6MWD included age, sex, height, weight and HR(max) % pred (adjusted r² = 0.38; p < 0.001), but there was variability across centres (adjusted r² = 0.09-0.73) and its routine use is not recommended. Age had a great impact in 6MWD independent of the centres, declining significantly in the older population (p < 0.001). Age-specific reference standards of 6MWD were constructed for male and female adults. In healthy subjects, there were geographic variations in 6MWD and caution must be taken when using existing predictive equations. The present study provides new 6MWD standard curves that could be useful in the care of adult patients with chronic diseases.
Launching and manipulation of polaritons in van der Waals materials offers novel opportunities for field-enhanced molecular spectroscopy and photodetection, among other applications. Particularly, ...the highly confined hyperbolic phonon polaritons (HPhPs) in h-BN slabs attract growing interest for their capability of guiding light at the nanoscale. An efficient coupling between free space photons and HPhPs is, however, hampered by their large momentum mismatch. Here, we show -by far-field infrared spectroscopy, infrared nanoimaging and numerical simulations- that resonant metallic antennas can efficiently launch HPhPs in thin h-BN slabs. Despite the strong hybridization of HPhPs in the h-BN slab and Fabry-Pérot plasmonic resonances in the metal antenna, the efficiency of launching propagating HPhPs in h-BN by resonant antennas exceeds significantly that of the non-resonant ones. Our results provide fundamental insights into the launching of HPhPs in thin polar slabs by resonant plasmonic antennas, which will be crucial for phonon-polariton based nanophotonic devices.
Neuroinflammation in Movement Disorders Saavedra-López, E.; Casanova, P.V.; Cribaro, G.P. ...
Handbook of Basal Ganglia Structure and Function,
01/2016, Volume:
24
Book Chapter, Reference
Peer reviewed
Neuroinflammation is present in almost every injury of the central nervous system. This response is intended to resolve tissue damage and restore homeostasis. However, in pathological conditions, ...inflammation may cause direct damage and contribute to neuronal degeneration. Many, if not all, movement disorders show neuroinflammatory changes in the areas of tissue degeneration. Debate still persists on whether these inflammatory changes are a mere consequence or a cause of the local damage. Increasing data suggest the latter, since a broad range of pathological alterations, including genetic, are able to modify the inflammatory scenario and induce or at least contribute to the appearance of movement disorders. In the present chapter, we review inflammatory-mediated alterations in the most prevalent movement disorders, emphasizing the paradigm of Parkinson's disease, and suggest that anti-inflammatory drugs may be a positive therapeutic option for movement disorders.
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