Inflammatory reaction in the retina after focal non-convulsive status epilepticus in mice investigated with high resolution magnetic resonance and diffusion tensor imaging

Pathophysiological consequences of focal non-convulsive status epilepticus (fNCSE) have been difficult to demonstrate in humans. In rats fNCSE pathology has been identified in the eyes. Here we evaluated the use of high-resolution 7 T structural T1-weighted magnetic resonance imaging (MRI) and 9.4 T diffusion tensor imaging (DTI) for detecting hippocampal fNCSE-induced retinal pathology ex vivo in mice. Seven weeks post-fNCSE, increased number of Iba1+ microglia were evident in the retina ipsilateral to the hemisphere with fNCSE, and morphologically more activated microglia were found in both ipsi- and contralateral retina compared to non-stimulated control mice. T1-weighted intensity measurements of the contralateral retina showed a minor increase within the outer nuclear and plexiform layers of the lateral retina. T1-weighted measurements were not performed in the ipsilateral retina due to technical difficulties. DTI fractional anisotropy(FA) values were discretely altered in the lateral part of the ipsilateral retina and unaltered in the contralateral retina. No changes were observed in the distal part of the optic nerve. The sensitivity of both imaging techniques for identifying larger retinal alteration was confirmed ex vivo in retinitis pigmentosa mice where a substantial neurodegeneration of the outer retinal layers is evident. With MR imaging a 50 % decrease in DTI FA values and significantly thinner retina in T1-weighted images were detected. We conclude that retinal pathology after fNCSE in mice is subtle and present bilaterally. High-resolution T1-weighted MRI and DTI independently did not detect the entire pathological retinal changes after fNCSE, but the combination of the two techniques indicated minor patchy structural changes

Metabolic control of arginine and ornithine levels paces the progression of leaf senescence

Pools of arginine and ornithine generated during protein degradation can pace the progression of leaf senescence by affecting the TCA cycle, polyamine biosynthesis and the ethylene signaling pathway.Leaf senescence can be induced by stress or aging, sometimes in a synergistic manner. It is generally acknowledged that the ability to withstand senescence-inducing conditions can provide plants with stress resilience. Although the signaling and transcriptional networks responsible for a delayed senescence phenotype, often referred to as a functional stay-green trait, have been actively investigated, very little is known about the subsequent metabolic adjustments conferring this aptitude to survival. First, using the individually darkened leaf (IDL) experimental setup, we compared IDLs of wild-type (WT) Arabidopsis (Arabidopsis thaliana) to several stay-green contexts, that is IDLs of two functional stay-green mutant lines, oresara1-2 (ore1-2) and an allele of phytochrome-interacting factor 5 (pif5), as well as to leaves from a WT plant entirely darkened (DP). We provide compelling evidence that arginine and ornithine, which accumulate in all stay-green contexts-likely due to the lack of induction of amino acids (AAs) transport-can delay the progression of senescence by fueling the Krebs cycle or the production of polyamines (PAs). Secondly, we show that the conversion of putrescine to spermidine (SPD) is controlled in an age-dependent manner. Thirdly, we demonstrate that SPD represses senescence via interference with ethylene signaling by stabilizing the ETHYLENE BINDING FACTOR1 and 2 (EBF1/2) complex. Taken together, our results identify arginine and ornithine as central metabolites influencing the stress- and age-dependent progression of leaf senescence. We propose that the regulatory loop between the pace of the AA export and the progression of leaf senescence provides the plant with a mechanism to fine-tune the induction of cell death in leaves, which, if triggered unnecessarily, can impede nutrient remobilization and thus plant growth and survival

Interleukin-17A during Local and Systemic Staphylococcus aureus-Induced Arthritis in Mice▿

Staphylococcus aureus is one of the dominant pathogens that induce septic arthritis in immunocompromised hosts, e.g., patients suffering from rheumatoid arthritis treated with immunosuppressive drugs. S. aureus-induced arthritis leads to severe joint destruction and high mortality despite antibiotic treatment. Recently, interleukin-17A (IL-17A) has been discovered to be an important mediator of aseptic arthritis both in mice and humans, but its function in S. aureus-induced arthritis is largely unknown. Here, we investigated the role of IL-17A in host defense against arthritis following systemic and local S. aureus infection in vivo. IL-17A knockout mice and wild-type mice were inoculated systemically (intravenously) or locally (intra-articularly) with S. aureus. During systemic infection, IL-17A knockout mice lost significantly more weight than the wild-type mice did, but no differences were found in the mortality rate. The absence of IL-17A had no impact on clinical arthritis development but led to increased histopathological erosivity late during systemic S. aureus infection. Bacterial clearance in kidneys was increased in IL-17A knockout mice compared to the level in wild-type mice only 1 day after bacterial inoculation. During systemic S. aureus infection, serum IL-17F protein levels and mRNA levels in the lymph nodes were elevated in the IL-17A knockout mice compared to the level in wild-type mice. In contrast to systemic infection, the IL-17A knockout mice had increased synovitis and erosions and locally decreased clearance of bacteria 3 days after local bacterial inoculation. On the basis of these findings, we suggest that IL-17A is more important in local host defense than in systemic host defense against S. aureus-induced arthritis

Computer tomography of kidney cancer, algorithms of differential diagnostics

Bakalaura darba tēma: Nieru audzēju datortomogrāfiskā izmeklēšana, diferenciāldiagnostikas algoritmi. Tēmas aktualitāti pamato/nosaka – nepieciešams pētīt nieru audzēju diagnostikas iespējas ar datortomogrāfisko izmeklēšanas metodi, tai skaitā, izmantojot to diferenciāldiagnostikā. Diferenciāldiagnostikā rinda ir iespējamo stāvokļu vai slimību, kas varētu izraisīt simptomus, saraksts, kas sastādīts, pamatojoties uz informāciju par pašreizējiem pacienta simptomiem, medicīnisko vēsturi un fiziskās apskates rezultātiem. Darba mērķis: noteikt nieru audzēju diferenciāldiagnostikas algoritmu efektivitāti datortomogrāfiskajā izmeklēšanā. Pētniecības uzdevumi: 1.Raksturot nieru funkcijas un iespējamos funkcionālos traucējumus. 2.Aprakstīt nieru darbības traucējumu diagnostiku un datortomogrāfiskā izmeklēšanu. 3.Veikt pētījuma metodoloģijas izstrādi un veikt pētījumu. 4.Analizēt rezultātus, izdarīt secinājumus un izstrādāt ieteikumus. Pētniecības jautājums: Kādā veidā nieru audzēju datortomogrāfiskā izmeklēšana ietekmē diferenciāldiagnostikas algoritmu pielietošanas efektivitāti? Pētniecības metodes: literatūras analīze, empīriskā metode. Pētniecības instruments: datu apstrāde. Pētījuma rezultāti: 10% pacientu tika konstatētas angiomiolipomas. Angiomiolipoma ir labdabīgs audzējs. Lai gan angiomiolipoma ir labdabīgs audzējs, tam palielinoties, pieaug spontānas asiņošanas risks nierēs. Ir tikai divi gadījumi, kuros ir nieru audzēji. Līdz ar to varam secināt, ka sastopams izmeklējumos reti vai arī šādi pacienti netiek savlaicīgi nosūtīti uz radioloģiskajiem izmeklējumiem. Atslēgvārdi: nieru audzēji, funkcionālie traucējumi, datortomogrāfiskā izmeklēšana, nieru diagnostikas iespējasBachelor’s theme: Computer tomography of kidney cancer, algorithms of differential diagnostics. The topicality of the issue is justified/determined by that it is necessary to study the potentialities of diagnosis of kidney tumors by computed tomography examination method, including its use in the differential diagnosis. The differential diagnosis line is a list of possible conditions for diseases that could cause symptoms based on information about the patient's current symptoms, medical history, and physical examination results. Purpose of the work to determine the efficiency of differential diagnostic algorithms in computed tomography examination of kidney tumors. Research tasks: 1. To describe the renal function and possible functional disorders. 2. Describe the diagnosis and computed tomography examination of renal disorders. 3. To develop a research methodology and conduct research. 4. Analyze the results, present conclusions, and provide recommendations. Research question: How does computed tomography of kidney tumors influence the effectiveness of differential diagnostic algorithms? Research methods: literature analysis, empirical method. Research tool: data processing. Research results: Angiomyolipomas were detected in 10% of patients. Angiomyolipoma is a benign tumor. Although angiomyolipoma is a benign tumor, as it grows, the risk of spontaneous kidney bleeding increases. There are only two cases of kidney tumors. Therefore, it can be concluded that it is rare in investigations or there are problems of simple case detection

Increase in Net Activity of Serine Proteinases but Not Gelatinases after Local Endotoxin Exposure in the Peripheral Airways of Healthy Subjects

We tested the hypothesis that activation of the innate immune response induces an imbalance in the proteolytic homeostasis in the peripheral airways of healthy subjects, towards excess serine or gelatinase proteinase activity. During bronchoscopy, 18 healthy human subjects underwent intra-bronchial exposure to endotoxin and contra-lateral exposure to vehicle. Bronchoalveolar lavage (BAL) samples were harvested 24 or 48 hours (h) later. We quantified archetype proteinases, anti-proteinases, inflammatory BAL cells, and, importantly, total plus net proteinase activities using functional substrate assays. As expected, endotoxin exposure increased the concentrations of polymorphonuclear leukocytes (PMN's) and macrophages, of proteinases and the anti-proteinases tissue inhibitor of metalloproteinase-1, alpha-1-antitrypsin and, to a lesser extent, secretory leukoproteinase inhibitor, at both time points. Notably, at these time points, endotoxin exposure substantially increased the quantitative NE/SLPI ratio and the net serine proteinase activity corresponding to neutrophil elastase (NE). Endotoxin exposure also increased the total gelatinase activity corresponding to matrix metalloproteinase (MMP)-9; an activity dominating over that of MMP-2. However, endotoxin exposure had no impact on net gelatinolytic activity at 24 or 48 h after exposure. Thus, local activation of the innate immune response induces an imbalance towards increased net serine proteinase activity in the proteolytic homeostasis of the peripheral airways in healthy subjects. Hypothetically, this serine proteinase activity can contribute to tissue remodelling and hypersecretion via NE from PMN's, if it is triggered repeatedly, as might be the case in chronic inflammatory airway disorders

Change in PtO₂ (shown as both an absolute change (mmHg) and relative change (%)), tissue temperature and rectal temperature affected by the intervention condition of each experiment.

<p>Error bars show 95% confidence intervals. Where error bars do not cross zero, the intervention had a statistically significant effect compared with the control condition.</p

Representative data from one rat in experiment 1 (Insufflation of humidified-warm CO₂ vs exposure to ambient air).

<p>The shaded areas show each period of insufflation of humidified-warm CO₂. A rapid increase in both PtO₂ and tissue temperature is seen each time gas insufflation is started, and is reversed when insufflation is stopped.</p