Glutathione treatment protects the rat liver against injury after warm ischemia and Kupffer cell activation

Background/Aim: The generation of reactive oxygen species by activated Kupffer cells (KC) may contribute to reperfusion injury of the liver during liver transplantation or resection. The aim of our present studies was to investigate (1) prevention of hepatic reperfusion injury after warm ischemia by administration of the antioxidant glutathione (GSH) and (2) whether GSH confers protection through influences on KC toxicity. Methods: Isolated perfused rat livers were subjected to 1 h of warm ischemia followed by 90 min of reperfusion without (n = 5) or with GSH or catalase (n = 4-5 each). Selective KC activation by zymosan (150 mug/ml) in continuously perfused rat livers was used to investigate KC-related liver injury. Results: Postischemic infusion of 0.1, 0.5, 1.0 and 2.0 mM GSH, but not 0.05 mM GSH prevented reperfusion injury after warm ischemia as indicated by a marked reduction of sinusoidal LDH efflux by up to 83 +/- 13% (mean +/- SD; p < 0.05) and a concomitant significant improvement of postischemic bile flow by 58 +/- 27% (p < 0.05). A similar protection was conveyed by KC blockade with gadolinium chloride indicating prevention of KC-related reperfusion injury by postischemic GSH treatment. Postischemic treatment with catalase (150 U/ml) resulted in a reduction of LDH efflux by 40 +/- 9% (p < 0.05). Accordingly, catalase as well as GSH (0.1-2.0 mM) nearly completely prevented the increase in LDH efflux following selective :KC activation by zymosan in continously perfused rat livers. Conclusion: Postischemic administration of GSH protects the liver against reperfusion injury after warm ischemia. Detoxification of KC-derived hydrogen peroxide seem to be an important feature of the protective mechanisms. Copyright (C) 2002 S. Karger AG, Basel

In search of sleep biomarkers of Alzheimer's disease: K-Complexes do not discriminate between patients with mild cognitive impairment and healthy controls

The K-complex (KC) is one of the hallmarks of Non-Rapid Eye Movement (NREM) sleep. Recent observations point to a drastic decrease of spontaneous KCs in Alzheimer's disease (AD). However, no study has investigated when, in the development of AD, this phenomenon starts. The assessment of KC density in mild cognitive impairment (MCI), a clinical condition considered a possible transitional stage between normal cognitive function and probable AD, is still lacking. The aim of the present study was to compare KC density in AD/ MCI patients and healthy controls (HCs), also assessing the relationship between KC density and cognitive decline. Twenty amnesic MCI patients underwent a polysomnographic recording of a nocturnal sleep. Their data were compared to those of previously recorded 20 HCs and 20 AD patients. KCs during stage 2 NREM sleep were visually identified and KC densities of the three groups were compared. AD patients showed a significant KC density decrease compared with MCI patients and HCs, while no differences were observed between MCI patients and HCs. KC density was positively correlated with Mini-Mental State Examination (MMSE) scores. Our results point to the existence of an alteration of KC density only in a full-blown phase of AD, which was not observable in the early stage of the pathology (MCI), but linked with cognitive deterioratio

On one-way cellular automata with a fixed number of cells

We investigate a restricted one-way cellular automaton (OCA) model where the number of cells is bounded by a constant number k, so-called kC-OCAs. In contrast to the general model, the generative capacity of the restricted model is reduced to the set of regular languages. A kC-OCA can be algorithmically converted to a deterministic finite automaton (DFA). The blow-up in the number of states is bounded by a polynomial of degree k. We can exhibit a family of unary languages which shows that this upper bound is tight in order of magnitude. We then study upper and lower bounds for the trade-off when converting DFAs to kC-OCAs. We show that there are regular languages where the use of kC-OCAs cannot reduce the number of states when compared to DFAs. We then investigate trade-offs between kC-OCAs with different numbers of cells and finally treat the problem of minimizing a given kC-OCA

Crop coefficients, growth rates and quality of cool-season turfgrasses

Determination of crop coefficients (Kc), the ratio between actual (ETa) and reference evapotranspiration (ET0), is necessary to schedule irrigation. Our objective was to determine Kc, turf quality and growth rate under daily irrigation to field capacity (FC = −3 kPa tension) and drying. Minilysimeters installed in a green (mowing height 3–5 mm) and fairway (15 mm) were weighed during four periods of 4–10 days duration in 2009 and 2010. Crop coefficients on the second and subsequent days after irrigation were not significantly different among species and averaged 0.81 and 0.91 on green and fairway, respectively. On the first day after irrigation, the Kc varied from 1.67 to 2.85 and decreased in the order Agrostis capillaris > Festuca rubra ssp. litoralis > F. rubra ssp. commutata > A. stolonifera > A. canina on the green, and F. rubra ssp. litoralis > Lolium perenne > F.rubra ssp. rubra > Poa pratensis > F. rubra ssp. commutata on the fairway. Drying reduced the average daily height growth from 0.98 to 0.74 mm on the green and 1.97–1.72 mm on the fairway. Scores for turf quality were reduced but remained acceptable. Although the Kc during the first day after irrigation to FC may be overestimated due to latent soil heat and a possible oasis effect, we conclude that irrigation to FC should be avoided as it causes excessive water use

On the evolution of elastic properties during laboratory stick-slip experiments spanning the transition from slow slip to dynamic rupture

The physical mechanisms governing slow earthquakes remain unknown, as does the relationship between slow and regular earthquakes. To investigate the mechanism(s) of slow earthquakes and related quasi-dynamic modes of fault slip we performed laboratory experiments on simulated fault gouge in the double direct shear configuration. We reproduced the full spectrum of slip behavior, from slow to fast stick slip, by altering the elastic stiffness of the loading apparatus (k) to match the critical rheologic stiffness of fault gouge (kc). Our experiments show an evolution from stable sliding, when k>kc, to quasi-dynamic transients when k ~ kc, to dynamic instabilities when k<kc. To evaluate the microphysical processes of fault weakening we monitored variations of elastic properties. We find systematic changes in P wave velocity (Vp) for laboratory seismic cycles. During the coseismic stress drop, seismic velocity drops abruptly, consistent with observations on natural faults. In the preparatory phase preceding failure, we find that accelerated fault creep causes a Vp reduction for the complete spectrum of slip behaviors. Our results suggest that the mechanics of slow and fast ruptures share key features and that they can occur on same faults, depending on frictional properties. In agreement with seismic surveys on tectonic faults our data show that their state of stress can be monitored by Vp changes during the seismic cycle. The observed reduction in Vp during the earthquake preparatory phase suggests that if similar mechanisms are confirmed in nature high-resolution monitoring of fault zone properties may be a promising avenue for reliable detection of earthquake precursors

7-Keto-Cholesterol and Cholestan-3beta, 5alpha, 6beta-Triol Induce Eryptosis through Distinct Pathways Leading to NADPH Oxidase and Nitric Oxide Synthase Activation

BACKGROUND/AIMS: We showed that patho-physiological concentrations of either 7-keto-cholesterol (7-KC), or cholestane-3beta, 5alpha, 6beta-triol (TRIOL) caused the eryptotic death of human red blood cells (RBC), strictly dependent on the early production of reactive oxygen species (ROS). The goal of the current study was to assess the contribution of the erythrocyte ROS-generating enzymes, NADPH oxidase (RBC-NOX), nitric oxide synthase (RBC-NOS) and xanthine oxido-reductase (XOR) to the oxysterol-dependent eryptosis and pertinent activation pathways. METHODS: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, reactive oxygen/nitrogen species (RONS) and nitric oxide formation from 2',7'-dichloro-dihydrofluorescein (DCF-DA) and 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA) -dependent fluorescence, respectively; Akt1, phospho-NOS3 Ser1177, and PKCζ from Western blot analysis. The activity of individual 7-KC (7 μM) and TRIOL (2, μM) on ROS-generating enzymes and relevant activation pathways was assayed in the presence of Diphenylene iodonium chloride (DPI), N-nitro-L-arginine methyl ester (L-NAME), allopurinol, NSC23766 and LY294002, inhibitors in this order of RBC-NOX, RBC-NOS, XOR and upstream regulatory proteins Rac GTPase and phosphoinositide3 Kinase (PI3K); hemoglobin oxidation from spectrophotometric analysis. RESULTS: RBC-NOX was the target of 7-KC, through a signaling including Rac GTPase and PKCζ, whereas TRIOL caused activation of RBC-NOS according to the pathway PI3K/Akt, with the concurrent activity of a Rac-GTPase. In concomitance with the TRIOL-induced .NO production, formation of methemoglobin with global loss of heme were observed, ascribable to nitrosative stress. XOR, activated after modification of the redox environment by either RBC-NOX or RBC-NOS activity, concurred to the overall oxidative/nitrosative stress by either oxysterols. When 7-KC and TRIOL were combined, they acted independently and their effect on ROS/RONS production and PS exposure appeared the result of the effects of the oxysterols on RBC-NOX and RBC-NOS. CONCLUSION: Eryptosis of human RBCs may be caused by either 7-KC or TRIOL by oxidative/nitrosative stress through distinct signaling cascades activating RBC-NOX and RBC-NOS, respectively, with the complementary activity of XOR; when combined, the oxysterols act independently and both concur to the final eryptotic effect

Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs