Dose-dependent scavenging activity of the ultra-short-acting ß1-blocker landiolol against specific free radicals.

Landiolol, a highly cardioselective ultra-short-acting ß1-blocker, prevents perioperative atrial fibrillation associated with systemic inflammation and oxidative stress. We evaluated the direct scavenging activity of landiolol against multiple free radical species. Nine free radical species (hydroxyl, superoxide anion, ascorbyl, tert-butyl peroxyl, tert-butoxyl, singlet oxygen, 2,2-diphenyl-1-picrylhydrazyl, nitric oxide, and tyrosyl radicals) were directly quantified using an X-band ESR spectrometer with the spin-trapping method. IC50 and reaction rate constants were estimated from the dose-response curve for each free radical. Landiolol scavenged six of the free radical species examined: hydroxyl radical (IC50 = 0.76 mM, k landiolol = 1.4 × 10|10 M|-1 s|-1, p<0.001), superoxide anion (58 mM, 2.1 M|-1 s|-1, p = 0.044), tert-butoxyl radical (4.3 mM, k landiolol/k CYPMPO = 0.77, p<0.001), ascorbyl free radical (0.31 mM, p<0.001), singlet oxygen (0.69 mM, k landiolol/k 4-OH |TEMP = 2.9, p<0.001), and nitric oxide (15 mM, 1.7 × 10 M|-1 s|-1, p<0.001). This study is the first to report that landiolol dose-dependently scavenges multiple free radical species with different reaction rate constants. These results indicate the potential clinical application of landiolol as an antioxidative and anti-inflammatory agent in addition to its present clinical use as an anti-arrhythmic agent.

Influence of aging on the color visual field in humans: A cross-sectional study.

ABSTRACT: Age-related narrowing of the visual field is observed in the elderly, which leads to reduced cognitive and psychomotor functions. The aim of the present cross-sectional study was to determine the influence of aging on the visual field for color vision in humans, with respect to angular thresholds for object detection and color detection.The subjects were divided into the elderly group (mean 76.1-year-old [70-89]) and the control group (25.2 [18-47]). Visual fields for different colors (blue, green, yellow, and red) were measured by manual kinetic perimetry and evaluated in terms of 2 measures of visual-field width: angular thresholds for object detection and those for color detection.While angular thresholds for object detection were significantly wider than those for color detection in the control group (P < .001), there was no difference in the elderly group (P = .06). Moreover, angular thresholds for object detection were significantly wider in the control group than in the elderly group (P = .019), but angular thresholds for color detection were not significantly different between the 2 groups (P = .903).The observed age-related changes in angular thresholds for object detection in color vision may reflect an age-related reduction in rod function. Stable cone function might explain the preserved angular thresholds for color detection in the elderly.

Re-employment of people with chronic stroke: A single-centre retrospective study.

BACKGROUND/AIM: Re-employment is the goal of rehabilitation for many patients after stroke. This study retrospectively examined previously employed stroke survivors who were unable to return to work at time of discharge from hospital and identified factors which were correlated with successful re-employment following a rehabilitation programme involving occupational therapy at a support facility. Factors correlated with reactivation of drivers' licence after stroke were also investigated. METHODS: Participants were 150 post-stroke patients who were discharged from a support facility for persons with disabilities from April 2011 to March 2016. Data on patients' sociodemographic information, activities of daily living, and physical functions had been recorded at the time of admission into the facility. Employment status was recorded at discharge. Data were collected retrospectively in July 2017 from the medical records. Logistic regression models were prepared to examine factors correlated with successful re-employment and reactivation of drivers' licence after occupational therapy. RESULTS: A stepwise logistic regression model revealed that the following four factors were significantly correlated with successful re-employment: (i) the dressing-lower body item in the Functional Independence Measure (P < 0.001), (ii) the grooming item in the Functional Independence Measure (P = 0.002), (iii) marital status (P = 0.007), and (iv) the problem-solving item in the Functional Independence Measure (P = 0.028). Another stepwise logistic regression model revealed that the factors were significantly correlated with successful reactivation of drivers' licence: (i) the problem-solving item in the Functional Independence Measure (P = 0.002), (ii) the dressing-lower body item in the Functional Independence Measure (P = 0.011) and (iii) the residence area (P = 0.038). CONCLUSION: A single-centre retrospective study demonstrated several significant correlates of successful re-employment and reactivation of drivers' licence after stroke following rehabilitation training which employs occupational therapy to target skills critical for employment.

Dose-dependency of multiple free radical-scavenging activity of edaravone.

BACKGROUND: Edaravone is a powerful free radical scavenger that is in clinical use. However, data concerning its dose-response relationship against multiple free radicals remain sparse. The purpose of the present study was to demonstrate the dose-dependency of direct scavenging activity of edaravone against multiple free radical species. MATERIALS AND METHODS: Free radical-scavenging activities of edaravone against six free radical species were evaluated by electron spin resonance spectroscopy using spin-trapping method. RESULTS: Edaravone scavenged the following free radicals in dose-dependent manners with reaction rate constants (kedaravone) or 50% inhibitory concentration (IC50) as indicated: hydroxyl radical (kedaravone = 5.2 × 1010 M-1 s-1), superoxide anion (kedaravone/kG-CYPMPO = 0.63), tert-butyl peroxyl radical (kedaravone/kG-CYPMPO = 8.8), ascorbyl free radical (IC50 = 0.17 ± 0.06 mM), 2,2-diphenyl-1-picrylhydrazyl (DPPH, IC50 = 4.7 ± 0.3 µM), and nitric oxide (kedaravone = 7.0 × 103 M-1 s-1). CONCLUSIONS: The dose-dependent scavenging activities of edaravone against multiple free radical species were clearly illustrated. It is speculated that edaravone acts as antioxidant by dose-dependently scavenging multiple free radical species along the chain reactions of oxidative stress in surgery.

Dependence of behavioral performance on material category in an object-grasping task with monkeys.

Material perception is an essential part of our cognitive function that enables us to properly interact with our complex daily environment. One important aspect of material perception is its multimodal nature. When we see an object, we generally recognize its haptic properties as well as its visual properties. Consequently, one must examine behavior using real objects that are perceived both visually and haptically to fully understand the characteristics of material perception. As a first step, we examined whether there is any difference in the behavioral responses to different materials in monkeys trained to perform an object grasping task in which they saw and grasped rod-shaped real objects made of various materials. We found that the monkeys' behavior in the grasping task, which was measured based on the success rate and the pulling force, differed depending on the material category. Monkeys easily and correctly grasped objects of some materials, such as metal and glass, but failed to grasp objects of other materials. In particular, monkeys avoided grasping fur-covered objects. The differences in the behavioral responses to the material categories cannot be explained solely based on the degree of familiarity with the different materials. These results shed light on the organization of multimodal representation of materials, where their biological significance is an important factor. In addition, a monkey that avoided touching real fur-covered objects readily touched images of the same objects presented on a CRT display. This suggests that employing real objects is important when studying behaviors related to material perception. NEW & NOTEWORTHY We tested monkeys using an object-grasping task in which monkeys saw and grasped rod-shaped real objects made of various materials. We found that the monkeys' behavior differed dramatically across the material categories and that the behavioral differences could not be explained solely based on the degree of familiarity with the different materials. These results shed light on the organization of multimodal representation of materials, where the biological significance of materials is an important factor.

Crossmodal Association of Visual and Haptic Material Properties of Objects in the Monkey Ventral Visual Cortex.

Just by looking at an object, we can recognize its non-visual properties, such as hardness. The visual recognition of non-visual object properties is generally accurate [1], and influences actions toward the object [2]. Recent studies suggest that, in the primate brain, this may involve the ventral visual cortex, which represents objects in a way that reflects not only visual but also non-visual object properties, such as haptic roughness, hardness, and weight [3-7]. This new insight raises a fundamental question: how does the visual cortex come to represent non-visual properties--knowledge that cannot be acquired directly through vision? Here we addressed this unresolved question using fMRI in macaque monkeys. Specifically, we explored whether and how simple visuo-haptic experience--just seeing and touching objects made of various materials--can shape representational content in the visual cortex. We measured brain activity evoked by viewing images of objects before and after the monkeys acquired the visuo-haptic experience and decoded the representational space from the activity patterns [8]. We show that simple long-term visuo-haptic experience greatly impacts representation in the posterior inferior temporal cortex, the higher ventral visual cortex. After the experience, but not before, the activity pattern in this region well reflected the haptic material properties of the experienced objects. Our results suggest that neural representation of non-visual object properties in the visual cortex emerges through long-term crossmodal exposure to objects. This highlights the importance of unsupervised learning of crossmodal associations through everyday experience [9-12] for shaping representation in the visual cortex.

Color vision test for dichromatic and trichromatic macaque monkeys.

Dichromacy is a color vision defect in which one of the three cone photoreceptors is absent. Individuals with dichromacy are called dichromats (or sometimes "color-blind"), and their color discrimination performance has contributed significantly to our understanding of color vision. Macaque monkeys, which normally have trichromatic color vision that is nearly identical to humans, have been used extensively in neurophysiological studies of color vision. In the present study we employed two tests, a pseudoisochromatic color discrimination test and a monochromatic light detection test, to compare the color vision of genetically identified dichromatic macaques (Macaca fascicularis) with that of normal trichromatic macaques. In the color discrimination test, dichromats could not discriminate colors along the protanopic confusion line, though trichromats could. In the light detection test, the relative thresholds for longer wavelength light were higher in the dichromats than the trichromats, indicating dichromats to be less sensitive to longer wavelength light. Because the dichromatic macaque is very rare, the present study provides valuable new information on the color vision behavior of dichromatic macaques, which may be a useful animal model of human dichromacy. The behavioral tests used in the present study have been previously used to characterize the color behaviors of trichromatic as well as dichromatic new world monkeys. The present results show that comparative studies of color vision employing similar tests may be feasible to examine the difference in color behaviors between trichromatic and dichromatic individuals, although the genetic mechanisms of trichromacy/dichromacy is quite different between new world monkeys and macaques.

Vitamin E derivative ETS-GS reduces liver ischemia-reperfusion injury in rats.

BACKGROUND: Ischemic liver injury is often the result of surgical procedures such as liver transplantation and hepatic resection. Liver damage occurs after reperfusion, leading to increased systemic inflammation. Recent studies have reported that vitamin E and glutathione can ameliorate ischemia-reperfusion (I/R) injury. In the present study, we evaluated the ability of a new vitamin E derivative, ETS-GS, to improve liver I/R injury. MATERIALS AND METHODS: Male Wistar received a subcutaneous injection of ETS-GS (10 mg/kg) or saline before experimentally-induced liver I/R injury or sham treatment. The rats were sacrificed after the 60-min ischemia and 24-h reperfusion. Histology and serum levels of cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-6, and high-mobility group box 1 (HMGB1) protein] and liver enzymes were determined to evaluate the protective effects of ETS-GS. RESULTS: We found that ETS-GS treatment attenuated I/R-induced histologic alterations, reduced levels of liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH). In addition, ETS-GS treatment decreased serum cytokine levels. CONCLUSIONS: Taken together, our results demonstrate that ETS-GS attenuates I/R injury in a rat model and suggests that ETS-GS may exert anti-inflammatory effects. Accordingly, ETS-GS may have therapeutic potential to treat various clinical conditions involving I/R injury.

Human atrial natriuretic peptide attenuates renal ischemia-reperfusion injury.

BACKGROUND: Acute kidney injury (AKI) is common in the intensive care unit, and one of its primary causes is renal ischemia-reperfusion (I/R) injury. Human atrial natriuretic peptide (hANP) exerts various pharmacologic effects, including renal protection. In the present study, we evaluated the renal protective effect of hANP in a rat model of renal I/R. MATERIALS AND METHODS: Male Wistar rats were divided into three groups that received the following treatments: induction of renal I/R (I/R group); continuous intravenous injection of hANP followed 30 min later by induction of renal I/R (hANP+I/R group); and sham treatment (control group). Rats were sacrificed after 60 min of ischemia and 24 h of reperfusion or sham treatment. To evaluate the renal protective effects if hANP, serum blood urea nitrogen (BUN) and creatinine (Cre) concentrations were determined, kidneys were histologically assessed, and serum biomarkers of oxidative stress were evaluated. In addition, antimycin A (AMA)-stimulated RAW264.7 cells were treated with hANP to assess its antioxidant effects. RESULTS: Serum BUN and Cre levels were elevated in the I/R group; however, these increases were significantly inhibited in the hANP + I/R group. Similarly, kidney tissue damage observed in the I/R group was attenuated in the hANP + I/R group. In vitro, AMA-stimulated cells treated with hANP showed reduced reactive oxygen species activity compared to cells treated with AMA alone. CONCLUSIONS: Our findings indicate that hANP may be effective in the treatment of various types of I/R injuries.

Auditory thalamic reticular nucleus of the rat: anatomical nodes for modulation of auditory and cross-modal sensory processing in the loop connectivity between the cortex and thalamus.

The auditory sector of the thalamic reticular nucleus (TRN) plays a pivotal role in gain and/or gate control of auditory input relayed from the thalamus to cortex. The TRN is also likely involved in cross-modal sensory processing for attentional gating function. In the present study, we anatomically examined how cortical and thalamic afferents intersect in the auditory TRN with regard to these two functional pathways. Iontophoretic injections of biocytin into subregions of the auditory TRN, which were made with the guidance of electrophysiological recording of auditory response, resulted in retrograde labeling of cortical and thalamic cells, indicating the sources of afferents to the TRN. Cortical afferents from area Te1 (temporal cortex, area 1), which contains the primary and anterior auditory fields, topographically intersected thalamic afferents from the ventral division of the medial geniculate nucleus at the subregions of the auditory TRN, suggesting tonotopically organized convergence of afferents, although they innervated a given small part of the TRN from large parts. In the caudodorsal and rostroventral parts of the auditory TRN, cortical afferents from nonprimary visual and somatosensory areas intersected thalamic afferents from auditory, visual, and somatosensory nuclei. Furthermore, afferents from the caudal insular cortex and the parvicellular part of the ventral posterior thalamic nucleus, which are associated with visceral processing, converged to the rostroventral end of the auditory TRN. The results suggest that the auditory TRN consists of anatomical nodes that mediate tonotopic and/or cross-modal modulation of auditory and other sensory processing in the loop connectivity between the cortex and thalamus.

Activation of mitogen-activated protein kinase in descending pain modulatory system.

The descending pain modulatory system is thought to undergo plastic changes following peripheral tissue injury and exerts bidirectional (facilitatory and inhibitory) influence on spinal nociceptive transmission. The mitogen-activated protein kinases (MAPKs) superfamily consists of four main members: the extracellular signal-regulated protein kinase1/2 (ERK1/2), the c-Jun N-terminal kinases (JNKs), the p38 MAPKs, and the ERK5. MAPKs not only regulate cell proliferation and survival but also play important roles in synaptic plasticity and memory formation. Recently, many studies have demonstrated that noxious stimuli activate MAPKs in several brain regions that are components of descending pain modulatory system. They are involved in pain perception and pain-related emotional responses. In addition, psychophysical stress also activates MAPKs in these brain structures. Greater appreciation of the convergence of mechanisms between noxious stimuli- and psychological stress-induced neuroplasticity is likely to lead to the identification of novel targets for a variety of pain syndromes.

EPCK1, a vitamin C and E analogue, reduces endotoxin-induced systemic inflammation in mice.

BACKGROUND: Phosphate ester of vitamin C and vitamin E (EPCK1), a strong antioxidant, is a water- and lipid-soluble phosphate ester of vitamin C and vitamin E. In the current study, we tested whether EPCK1 inhibits oxidative stress and prevents systemic inflammation. MATERIALS AND METHODS: Mice were randomly divided into a negative control group, a lipopolysaccharide (LPS)-induced sepsis group, and a group treated with an intraperitoneal infusion of EPCK1 (10 mg/kg) prior to or following LPS administration. In addition, RAW 264.7 cells were treated with LPS in the presence or absence of EPCK1. We examined levels of high mobility group box 1 (HMGB1) protein and inducible nitric oxide synthase (iNOS) in both in vivo and in vitro experiments, and liver histopathology in the in vivo experiment. RESULTS: Liver histopathology significantly improved in the EPCK1 group compared with the LPS group. Although LPS administration increased HMGB1 and nitric oxide (NO) secretion, EPCK1 decreased the secretion of these mediators in vitro and in vivo. CONCLUSIONS: Our findings suggest that EPCK1 may inhibit inflammation and potentially function as a novel anti-inflammatory therapeutic agent.

ETS-GS, a new antioxidant, ameliorates renal ischemia-reperfusion injury in a rodent model.

BACKGROUND: Ischemia-reperfusion (I/R) contributes to acute kidney injury (AKI). On the other hand, anti-oxidative drugs help to prevent renal injury caused by I/R. The current study examined whether a new antioxidant, ETS-GS, inhibits reactive oxygen species (ROS) generation and thereby prevents renal I/R injury in rodent models. METHODS: Rats with experimentally-induced renal I/R injury were treated concurrently with an intravenous injection of either ETS-GS or saline. Anesthesia was induced with sevoflurane. RESULTS: Histologic examination revealed marked reduction of interstitial congestion, edema, inflammation, and hemorrhage in kidney tissue harvested 24 h after ETS-GS treatment. Renal I/R-induced secretion of nitric oxide (NO) in serum was inhibited by ETS-GS treatment. Furthermore, malondialdehyde (MDA) levels in the kidney were significantly lower in ETS-GS-treated rats with renal I/R. Moreover, when murine macrophage-like RAW264.7 cells were stimulated with antimycin A in the presence or absence of simultaneous ETS-GS treatment, ETS-GS decreased ROS levels. CONCLUSIONS: Thus, ETS-GS lowered ROS levels in cultured cells, reduced serum NO levels, decreased renal MDA levels, and protected rats against I/R-induced kidney injury. Given these in vitro and in vivo findings, ETS-GS is a strong candidate for future exploration of therapeutic potential in various human I/R diseases.

ETS-GS, a new anti-oxidative drug, protects against lipopolysaccharide-induced acute lung and liver injury.

BACKGROUND: Sepsis is a major health threat that remains refractory to treatment. Impairment of normal cellular function due to oxidative stress is implicated in organ injury during systemic inflammatory responses. We investigated whether the new anti-oxidative drug, ETS-GS, could inhibit secretion of cytokines and mono-nitrogen oxides, thus reducing organ damage in a rat model of lipopolysaccharide-induced sepsis. MATERIALS AND METHODS: Lipopolysaccharide was administered intravenously to male Wistar rats in order to establish a rat model of systemic inflammation. These rats were challenged with or without intravenous ETS-GS. Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide, with or without simultaneous ETS-GS treatment, in order to elucidate the mechanism of action. RESULTS: Histologic examination revealed that ETS-GS markedly reduced lipopolysaccharide-induced interstitial edema and leukocytic infiltration in lung tissue, and lipopolysaccharide-induced bleeding and leukocytic infiltration in liver tissue harvested 12 h after treatment. Cytokine (interleukin-6 and tumor necrosis factor-α) secretion was strongly induced by lipopolysaccharide; this induction was similarly inhibited by ETS-GS treatment. Likewise, lipopolysaccharide-induced secretion of mono-nitrogen oxides was inhibited by ETS-GS. In the in vitro studies, ETS-GS administration inhibited IκB phosphorylation. CONCLUSION: ETS-GS blocked the lipopolysaccharide-induced inflammatory response and protected against acute lung and liver injury normally associated with endotoxemia in this rat model of systemic inflammation. Further, this protection may be mediated through the inhibition of nuclear factor κ-light-chain-enhancer of activated B cells activation. Our results suggest that ETS-GS is a potential therapeutic agent for sepsis.

Putative pyramidal neurons and interneurons in the monkey parietal cortex make different contributions to the performance of a visual grouping task.

Visual grouping of discrete elements is an important function for object recognition. We recently conducted an experiment to study neural correlates of visual grouping. We recorded neuronal activities while monkeys performed a grouping detection task in which they discriminated visual patterns composed of discrete dots arranged in a cross and detected targets in which dots with the same contrast were aligned horizontally or vertically. We found that some neurons in the lateral bank of the intraparietal sulcus exhibit activity related to visual grouping. In the present study, we analyzed how different types of neurons contribute to visual grouping. We classified the recorded neurons as putative pyramidal neurons or putative interneurons, depending on the duration of their action potentials. We found that putative pyramidal neurons exhibited selectivity for the orientation of the target, and this selectivity was enhanced by attention to a particular target orientation. By contrast, putative interneurons responded more strongly to the target stimuli than to the nontargets, regardless of the orientation of the target. These results suggest that different classes of parietal neurons contribute differently to the grouping of discrete elements.

Hydrogen-rich saline solution attenuates renal ischemia-reperfusion injury.

PURPOSE: Renal ischemia-reperfusion (I/R), an important cause of acute kidney injury, is unavoidable during various types of operations, including renal transplantation, surgical revascularization of the renal artery, partial nephrectomy, and treatment of suprarenal aortic aneurysms. Exacerbation of I/R injury is mediated by reactive oxygen species (ROS). A recent study has shown that hydrogen has antioxidant properties. In this study, we tested the hypothesis that a hydrogen-rich saline solution (HRSS) attenuates renal I/R injury in a rodent model. METHODS: Rats were treated with an intravenous injection of HRSS or control saline solution followed by renal I/R. After 24 h of treatment, we performed a histological examination and transmission electron microscopy, and measured serum levels of 8-OHdG. RESULTS: Histological analysis revealed a marked reduction of interstitial congestion, edema, inflammation, and hemorrhage in renal tissue harvested 24 h after HRSS treatment compared to saline administration. Renal I/R injury, which led to altered mitochondrial morphology, was also inhibited by HRSS. Furthermore, serum 8-OHdG levels were significantly lower in rats treated with HRSS and subjected to renal I/R. CONCLUSIONS: These protective effects were likely due to the antioxidant properties of HRSS. These results suggest that HRSS is a potential therapeutic candidate for treating various I/R diseases.

Human atrial natriuretic peptide ameliorates LPS-induced acute lung injury in rats.

Acute lung injury, a common component of systemic inflammatory disease, is a life-threatening condition without many effective treatments. However, recent studies have demonstrated that the multifunctional human atrial natriuretic peptide (hANP) exerts anti-inflammatory effects. Therefore, we tested the hypothesis that hANP could prevent lipopolysaccharide (LPS)-induced acute lung injury in a rodent model. Rats received an LPS injection and continuous intravenous infusion (CIV) of hANP or saline solution. We evaluated the anti-inflammatory effects of hANP by histological examination and determination of serum cytokine levels and lung myeloperoxidase (MPO) activity. Histological examination revealed marked reductions in interstitial congestion, edema, inflammation, and hemorrhage in lung tissue harvested 12 h after hANP treatment compared with tissue from rats that received saline treatment after LPS. LPS injection induced elevated cytokine (IL-1beta and IL-6) secretion and lung MPO activity, which was also attenuated by hANP treatment. Taken together, these data demonstrate that hANP exerts an anti-inflammatory effect and may have potential as a therapeutic agent to treat systemic inflammatory diseases.

An electron spin resonance study for real-time detection of ascorbyl free radicals after addition of dimethyl sulfoxide in murine hippocampus or plasma during kainic acid-induced seizures.

Electron spin resonance (ESR)-silent ascorbate solutions generate a detectable, likely concentration-dependent signal of ascorbyl free radicals (AFR) immediately upon addition of a molar excess of dimethyl sulfoxide (DMSO). We aimed to perform quantitative ESR analysis of AFR in real time after addition of DMSO (AFR/DMSO) to evaluate ascorbate concentrations in fresh hippocampus or plasma following systemic administration of kainate in mice. Use of a special tissue-type quartz cell allowed immediate detection of AFR/DMSO ESR spectra in fresh tissues from mice. AFR/DMSO content was increased significantly in fresh hippocampus or plasma obtained during kainate-induced seizures of mice, reaching maximum levels at 90 min after intraperitoneal administration of 50 mg/kg kainic acid. This suggests that oxidative injury of the hippocampus resulted from the accumulation of large amounts of ascorbic acid in the brain after kainic acid administration. AFR/DMSO content measured on an ESR spectrometer can be used for real-time evaluation of ascorbate content in fresh tissue. Due to the simplicity, good performance, low cost and real-time monitoring of ascorbate, this method may be applied to clinical research and treatment in the future.

The impact of oxidative stress levels on the clinical effectiveness of sivelestat in treating acute lung injury: an electron spin resonance study.

BACKGROUND: Sivelestat, a neutrophil elastase inhibitor, has been used to treat acute lung injury (ALI) with varying levels of clinical success. Variable baseline levels of oxidative stress in patients with ALI have been proposed as one explanation for inconsistent results. METHODS: Using a bedside electron spin resonance spectrometer, we evaluated electron spin resonance signal intensities of serum ascorbyl free radicals supplemented with dimethyl sulfoxide (AFR/DMSO) in patients with ALI. RESULTS: We found a positive correlation between AFR/DMSO and ascorbate levels, suggesting that serum AFR/DMSO measurements may serve as a surrogate for real-time assessments of oxidative stress. Levels of AFR/DMSO in patients with ALI were significantly lower than those found in healthy controls. Stratified analyses revealed that baseline AFR/DMSO levels were significantly lower in patients with ALI who failed to respond to sivelestat compared with those who did respond. CONCLUSIONS: Our results suggest that the clinical efficacy of sivelestat is dependent on baseline oxidative stress levels.

Cortico-geniculate feedback linking the visual fields surrounding the blind spot in the cat.

Previous studies have shown that neurons in layer 6 of V1 are activated by visual stimuli that induce perceptual filling-in at the blind spot (BS). As the main target of layer 6 neurons is the lateral geniculate nucleus (LGN), we speculate that the cortico-geniculate projection is involved in mediating filling-in at BS. To begin to test that hypothesis, we examined whether there is an anatomical basis for integration of visual signals from both sides of BS by cortico-geniculate feedback neurons in V1. We injected an anterograde tracer into a site adjacent to the region representing BS. We observed that numerous axons traverse the neuron-free gap that retinotopically corresponds to BS within LGN. This indicates that visual signals from one side of BS are conveyed to the opposite side via a feedback connection. Cortico-geniculate feedback projection may integrate visual signals from around BS and contribute to perceptual filling-in at BS.