Hyperglycemia-induced impairment of the blood-retinal barrier represents the main pathological event in diabetic retinopathy that is elicited by a reduced cellular response to an accumulation of reactive oxygen species (ROS) and increased inflammation. The purpose of the study was to evaluate whether the selective β1-adrenoreceptor (β1-AR) antagonist metoprolol could modulate the inflammatory response to hyperglycemic conditions. For this purpose, human retinal endothelial cells (HREC) were treated with normal (5 mM) or high glucose (25 mM, HG) in the presence of metoprolol (10 μM), epinephrine (1 μM), or both compounds. Metoprolol prevented both the HG-induced reduction of cell viability (MTT assays) and the modulation of the angiogenic potential of HREC (tube formation assays) reducing the TNF-α, IL-1β, and VEGF mRNA levels (qRT-PCR). Moreover, metoprolol prevented the increase in phospho-ERK1/2, phospho-cPLA2, COX2, and protein levels (Western blot) as well as counteracting the translocation of ERK1/2 and cPLA2 (high-content screening). Metoprolol reduced ROS accumulation in HG-stimulated HREC by activating the anti-oxidative cellular response mediated by the Keap1/Nrf2/HO-1 pathway. In conclusion, metoprolol exerted a dual effect on HG-stimulated HREC, decreasing the activation of the pro-inflammatory ERK1/2/cPLA2/COX2 axis, and counteracting ROS accumulation by activating the Keap1/Nrf2/HO-1 pathway.

Diabetic retinopathy (DR) is characterized by morphologic and metabolic alterations in endothelial cells (ECs) and pericytes (PCs) of the blood–retinal barrier (BRB). The loss of interendothelial junctions, increased vascular permeability, microaneurysms, and finally, EC detachment are the main features of DR. In this scenario, a pivotal role is played by the extensive loss of PCs. Based on previous results, the aim of this study was to assess possible beneficial effects exerted by adipose mesenchymal stem cells (ASCs) and their pericyte-like differentiated phenotype (P-ASCs) on human retinal endothelial cells (HRECs) in high glucose conditions (25 mM glucose, HG). P-ASCs were more able to preserve BRB integrity than ASCs in terms of (a) increased transendothelial electrical resistance (TEER); (b) increased expression of adherens junction and tight junction proteins (VE-cadherin and ZO-1); (c) reduction in mRNA levels of inflammatory cytokines TNF-α, IL-1β, and MMP-9; (d) reduction in the angiogenic factor VEGF and in fibrotic TGF-β1. Moreover, P-ASCs counteracted the HG-induced activation of the pro-inflammatory phospho-ERK1/2/phospho-cPLA2/COX-2 pathway. Finally, crosstalk between HRECs and ASCs or P-ASCs based on the PDGF-B/PDGFR-β axis at the mRNA level is described herein. Thus, P-ASCs might be considered valuable candidates for therapeutic approaches aimed at countering BRB disruption in DR.

Îòðàâëåíèÿ-ýòî íå òîëüêî îäíà èç ñàìûõ àêòóàëüíûõ ïðîáëåì, ñ êîòîðûìè ñòàëêèâàþòñÿ âëàäåëüöû êîøåê, íî è îäíà èç ñàìûõ çàãàäî÷íûõ ïàòîëîãèé, âåäü ïðè÷èíà çà÷àñòóþ îñòàåòñÿ äî êîíöà íå âûÿñíåííîé.  íàøåé ïðàêòè÷åñêîé äåÿòåëüíîñòè ìû ÷àñòî ïðèìåíÿåì ãàìàâèò è ôîñïðåíèë â ñîñòàâå êîìïëåêñíîé òåðàïèè îñòðûõ è õðîíè÷åñêèõ îòðàâëåíèé ó ìåëêèõ äîìàøíèõ aeèâîòíûõ (êîøåê è ñîáàê), â òîì ÷èñëå â ñëó÷àÿõ, êîãäà òîêñè÷åñêèé àãåíò íå áûë ÷åòêî âûÿâëåí.  äàííîé ðàáîòå ïðèâåäåíû 4 êëèíè÷åñêèõ ñëó÷àÿ õðîíè÷åñêîãî îòðàâëåíèÿ êîøåê â âîçðàñòå 6-8,5 ëåò âî âðåìÿ ïðîèñõîäÿùåãî â äîìå è â øêîëå ðåìîíòà. Ïî ðåçóëüòàòàì àíàëèçîâ ïîñòàâëåí äèàãíîç: õðîíè÷åñêàÿ èíòîêñèêàöèÿ íåîïðåäåëåííûì àãåíòîì, ãåïàòèò, òîêñè÷åñêîå ïîðàaeåíèå ïå÷åíè, ñïëåíî-è ãåïàòîìåãàëèÿ, õîëàíãèò, õîëåñòàç. Ïðè ïîñòóïëåíèè ó aeèâîòíûõ èìåëèñü âûðàaeåííûå îòêëîíåíèÿ â îáùåì àíàëèçå êðîâè (ëåéêîöèòîç, ýðèòðîïåíèÿ, ïîâûøåííàÿ ÑÎÝ), â ëåéêîãðàììå (ýîçèíîôèëèÿ), â áèîõèìè÷åñêîì àíàëèçå (ñíèaeåíèå óðîâíÿ îáùåãî áåëêà, ïîâûøåíèå óðîâíÿ ãëþêîçû, ïîâûøåíèå ËÄÃ, ÀÑÒ, ÀËÒ, ÙÔ, ÃÃÒ, áèëèðóáèíà).  2 ñëó÷àÿõ ãàìàâèò è ôîñïðåíèë ïîäêëþ÷àëè â ñîñòàâ êîìïëåêñíîãî ëå÷åíèÿ, ïðîâîäèâøåãîñÿ â äîìàøíèõ óñëîâèÿõ, à åùå â 2 ñëó÷àÿõ (êîíòðîëü) ýòè ïðåïàðàòû ê ñõåìå íå ïîäêëþ÷àëè. Êëèíè÷åñêîå âûçäîðîâëåíèå íàñòóïàëî íà 5-6 ñóòêè, ôîðìóëà êðîâè âîññòàíàâëèâàëàñü ÷åðåç 3-4 íåäåëè. Íîðìàëèçîâàëèñü ïîêàçàòåëè ÀÑÒ, ÀËÒ, ÃËÄÃ, ÙÔ è ÃÃÒ, à òàêaeå áèëèðóáèíà. Íàïðîòèâ, â êîíòðîëüíîé ãðóïïå äàííûå ïîêàçàòåëè ÷åðåç 2 ìåñÿöà òåðàïèè íå âåðíóëèñü ê íîðìàëüíîìó óðîâíþ. Ìû ñ÷èòàåì, ÷òî ïîäêëþ÷åíèå ãàìàâèòà è ôîñïðåíèëà ê ñõåìå òåðàïèè õðîíè-÷åñêîãî îòðàâëåíèÿ ó êîøåê ñïîñîáñòâóåò óñêîðåíèþ êëèíè-÷åñêîãî âûçäîðîâëåíèÿ è íîðìàëèçàöèè ôîðìóëû êðîâè. Poisoning is not only one of the most pressing problems that have been facing cat owners, but one of the most enigmatic pathologies as well, because the cause often remains the mistery. In our practice we often use Gamavit and Phosprenyl in the complex therapy of acute and chronic poisoning in pets, including cases where the toxic agent has not been elucidated.

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Background: Reactive oxygen species (ROS) accumulation plays a pivotal role in the onset of cell damage induced by hyperglycemia and represents one of the major factors in the pathogenesis of diabetic retinopathy. In this study, we tested the antioxidants cyanidin-3-O-glucoside (C3G) and verbascoside (Verb) in the protection of retinal endothelium against glucose toxicity "in vitro". Methods: Increasing amounts (5-50 µM) of C3G, Verb or the combination of both compounds were tested in Human Retinal Endothelial Cells (HREC) grown with normal glucose (5 mM, NG) or high glucose (25 mM, HG). Results: Reduced cell viability and enhanced ROS levels (evaluated by MTT and H2DCFDA assays, respectively) in HG-stimulated HREC were restored by C3G and Verb in a dose-dependent manner, achieving the maximum protection in the presence of both compounds. Moreover, co-treatment with C3G and Verb worked better than each single molecule alone in the prevention of the disruption of blood-retinal-barrier-like properties by HG in a confluent HREC monolayer, as assessed by trans endothelial electrical resistance (TEER) and Na-Fluorescein permeability assays. Accordingly, C3G and Verb together also better counteracted the HG-induced down-regulation of the tight junction membrane proteins Zonula Occludens-1 and VE-Cadherin evaluated by immunocytochemical and Western blot analyses. Conclusions: In conclusion, our data indicate that C3G and Verb could efficiently protect the retinal endothelium against high glucose damage.

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The stria vascularis (SV) contributes to cochlear homeostasis and consists of three layers, one of which contains the blood-labyrinthic barrier (BLB), with a large number of bovine cochlear pericytes (BCPs). Cisplatin is a chemotherapeutic drug that can damage the SV and cause hearing loss. In this study, cell viability, proliferation rate, cytotoxicity and reactive oxygen species production were evaluated. The protein content of phospho-extracellular signal-regulated kinases (ERK) 1/2, total ERK 1/2, phospho-cytosolic phospholipase A2 (cPLA2), total cPLA2 and cyclooxygenase 2 (COX-2) and the release of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) from BCPs were analyzed. Finally, the protective effect of platelet-derived growth factor (PDGF-BB) on BCPs treated with cisplatin was investigated. Cisplatin reduced viability and proliferation, activated ERK 1/2, cPLA2 and COX-2 expression and increased PGE2 and VEGF release; these effects were reversed by Dexamethasone. The presence of PDGF-BB during the treatment with cisplatin significantly increased the proliferation rate. No studies on cell regeneration in ear tissue evaluated the effect of the PDGF/Dex combination. The aim of this study was to investigate the effects of cisplatin on cochlear pericytes and propose new otoprotective agents aimed at preventing the reduction of their vitality and thus maintaining the BLB structure.