Gamma-Synuclein Dysfunction Causes Autoantibody Formation in Glaucoma Patients and Dysregulation of Intraocular Pressure in Mice.

Dysregulation of intraocular pressure (IOP) is one of the main risk factors for glaucoma. γ-synuclein is a member of the synuclein family of widely expressed synaptic proteins within the central nervous system that are implicated in certain types of neurodegeneration. γ-synuclein expression and localization changes in the retina and optic nerve of patients with glaucoma. However, the mechanisms by which γ-synuclein could contribute to glaucoma are poorly understood. We assessed the presence of autoantibodies to γ-synuclein in the blood serum of patients with primary open-angle glaucoma (POAG) by immunoblotting. A positive reaction was detected for five out of 25 patients (20%) with POAG. Autoantibodies to γ-synuclein were not detected in a group of patients without glaucoma. We studied the dynamics of IOP in response to IOP regulators in knockout mice (γ-KO) to understand a possible link between γ-synuclein dysfunction and glaucoma-related pathophysiological changes. The most prominent decrease of IOP in γ-KO mice was observed after the instillation of 1% phenylephrine and 10% dopamine. The total protein concentration in tear fluid of γ-KO mice was approximately two times higher than that of wild-type mice, and the activity of neurodegeneration-linked protein α2-macroglobulin was reduced. Therefore, γ-synuclein dysfunction contributes to pathological processes in glaucoma, including dysregulation of IOP.

A Pilot Study of Changes in the Level of Catecholamines and the Activity of α-2-Macroglobulin in the Tear Fluid of Patients with Parkinson's Disease and Parkinsonian Mice.

Development of differential and early (preclinical) diagnostics of Parkinson's disease (PD) is among the priorities in neuroscience. We searched for changes in the level of catecholamines and α-2-macroglobulin activity in the tear fluid (TF) in PD patients at an early clinical stage. It was shown that TF in patients is characterized by an increased level of noradrenaline mainly on the ipsilateral side of pronounced motor symptoms (72%, p = 0.049), a decreased level of adrenaline on both sides (ipsilateral-53%, p = 0.004; contralateral-42%, p = 0.02), and an increased α-2-macroglobulin activity on both sides (ipsilateral-53%, p = 0.03; contralateral-56%, p = 0.037) compared to controls. These changes are considered as potential biomarkers for differential diagnosis. Similar changes in the TF were found in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice when modeling clinical and preclinical stages of PD. These data show the adequacy of models to the pathogenesis of PD along the selected metabolic pathways, and also suggest that the found TF changes can be considered as potential biomarkers for preclinical diagnosis of PD. In Parkinsonian mice, the level of catecholamines also changes in the lacrimal glands, which makes it possible to consider them as one of the sources of catecholamines in the TF.

Secondary Radar Beacons for Local Ad-Hoc Autonomous Robot Localization Systems.

In this paper, we present a detailed analysis and implementation of secondary radar beacons designed for a local ad-hoc localization and landing system (LAOLa) to support the navigation of autonomous ground and aerial vehicles. We discuss a switched linear feedback network as a virtually coherent oscillator and show how to use it as a secondary radar transponder. Further, we present a signal model for the beat signal of the transponder response in an FMCW radar system, which is more detailed than in previously published papers. An actual transponder realization in the 24 GHz ISM band is presented. Its RF performance was evaluated both in the laboratory and in the field. Finally, we put forward some ideas on how to overcome the range measurement inaccuracy inherent in this transponder concept.

Diluted Calcium Hydroxylapatite for Skin Tightening of the Upper Arms and Abdomen.

BACKGROUND: The collagen-stimulating properties of Radiesse® (calcium hydroxylapatite, CaHA) can be used for skin-tightening procedures by hyper-diluting the product with lidocaine or saline. OBJECTIVE: To evaluate the effectiveness and safety of diluted CaHA for skin tightening in two case series of women with skin laxity in the upper arms or abdomen. METHODS: For each case series, 10 female subjects were enrolled. In the upper arms, CaHA diluted 1:2 with normal saline solution and 2% lidocaine was injected subdermally using a short, linear-threading technique. Skin elasticity was assessed at baseline and Months 1 and 3 using a cutometer. In the abdominal wall, CaHA diluted 1:4 with saline solution was injected subdermally using a linear-threading technique. Subjects underwent pre- and post-treatment (70 days) ultrasound scans to determine dermal thickness around the umbilicus and sides of the abdomen. Subjects and physicians assessed treatment outcomes using the 5-point Global Aesthetic Improvement Scale (GAIS). Adverse events and tolerability were recorded. RESULTS: Cutometry results for upper arm skin showed an increase in skin elasticity from 72 U at baseline to 82 U at Month 3 (P≤0.05). Ultrasound measures of the abdominal wall demonstrated statistically significant increases in dermal thickness after injection of diluted CaHA of 0.7 mm (umbilicus) and 0.4 mm (sides of abdomen). Diluted CaHA resulted in an overall increase in dermal thickness of 26.7% (P≤0.05). In both case series, 90% of subjects and physicians rated treatment outcomes on GAIS as much or very much improved. Treatment was well tolerated. CONCLUSIONS: Diluted CaHA improved skin elasticity and increased dermal thickness in the upper arms and abdomen after only a single treatment. The procedures were well tolerated, and subject and investigator satisfaction with treatment results was very high. Injection of diluted CaHA is an effective procedure for skin tightening in the upper arms and abdomen.

J Drugs Dermatol. 2017;16(9):900-906.

The role of oxidative stress in acute renal injury of newborn rats exposed to hypoxia and endotoxin.

Neonatal kidney injury is a frequent pathology, especially among premature infants. The search for effective nephroprotection requires the creation of adequate experimental models of nephropathy in newborns. In this study, we explored the development of acute kidney injury (AKI) in neonatal rats during hypoxia or administration of endotoxin. We found that 2-h hypoxia (8% O2 ) and the intraperitoneal injection of 4 mg·kg-1 lipopolysaccharide (LPS) causes the appearance of AKI markers, such as kidney injury molecule-1 (КIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the rat urine after 24 and 72 h of exposure. On the other hand, the levels of blood urine nitrogen under the same conditions rise only slightly. The damaging effects of hypoxia and endotoxin were accompanied by histological changes in the renal tissue and a significant decrease in the proliferation marker, (proliferating cell nuclear antigen). It is revealed that 3 h after the introduction of LPS, levels of reactive oxygen species in the kidney were significantly increased, and the injection of the antioxidant N-acetylcysteine afforded protection from AKI, evaluated by urine КIM-1 and NGAL levels. Thus, the simulation of AKI in newborn rat pups can be employed in screening for potential nephroprotective drugs, particularly among antioxidative compounds to be used in neonatology.