Continuous coloured light altered human brain haemodynamics and oxygenation assessed by systemic physiology augmented functional near-infrared spectroscopy.

Exposure to artificial coloured light is unavoidable in our modern life, but we are only just beginning to understand the impact of coloured light on human physiology. The aim of the present study was to determine effects of coloured light exposure on human systemic and brain physiology using systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). We measured changes in haemoglobin concentrations and tissue oxygen saturation in the left and right prefrontal cortices (L-PFC, R-PFC) by fNIRS, and also recorded skin conductance (SC), partial pressure of end-tidal CO2 (PETCO2), and heart-rate variability variables. 17 healthy adults (median age: 29 years, range: 25-65 years, 6 women) were exposed to blue, red, green, or yellow light for 10 minutes. Pre-light and post-light conditions were in darkness. In the L-PFC the yellow evoked a brain activation. SC and PETCO2 did not change during any of the coloured light exposures, but SC increased and PETCO2 decreased for all colours (except green) in the post-light period. Changes in L-PFC haemoglobin concentration were also observed during the post-light period but have to be interpreted with care, because heart rate and SC increased while PETCO2 decreased. The detected effects are potentially of high relevance for choosing room lighting and may possibly be applied therapeutically.

Physiological Effects of Continuous Colored Light Exposure on Mayer Wave Activity in Cerebral Hemodynamics: A Functional Near-Infrared Spectroscopy (fNIRS) Study.

We are increasingly exposed to colored light, but its impact on human physiology is not yet extensively investigated. In the present study we aimed to determine the effects of colored light on human cerebral Mayer wave activity (MWA). We measured oxy- ([O2Hb]), deoxy- ([HHb]), total hemoglobin ([tHb]) concentrations and tissue oxygen saturation (StO2) by functional near-infrared spectroscopy (fNIRS) in the left and right pre-frontal cortex (L-PFC, R-PFC) of 17 subjects (median age: 29 years, 6 women). In a randomized crossover design subjects were exposed to blue, red, green, and yellow LED light for 10 min. Pre-light (8 min, baseline) and post-light (15 min, recovery) conditions were darkness. MWA was calculated from band-pass filtered fNIRS signals (~0.08-0.12 Hz). The medians from the last 3 min of each period (baseline, light exposure, recovery) were statistically analyzed. MWA was increased during red and green light vs. baseline and after blue light exposure in recovery in the L-PFC. MWA differed depending on the chosen frequency range, filter design, and type of signals to analyze (raw intensity, hemoglobin signal from multi-distance method or modified Beer-Lambert law, or within hemoglobin signals).

Efficacy of a Nasal Spray from Citrus limon and Cydonia oblonga for the Treatment of Hay Fever Symptoms-A Randomized, Placebo Controlled Cross-Over Study.

Nasal spray from lemon and quince (LQNS) is used to treat hay fever symptoms and has been shown to inhibit histamine release from mast cells in vitro. Forty-three patients with grass pollen allergy (GPA) were randomized to be treated either with placebo or LQNS for one week, respectively, in a cross-over study. At baseline and after the respective treatments patients were provoked with grass pollen allergen. Outcome parameters were nasal flow measured with rhinomanometry (primary), a nasal symptom score, histamine in the nasal mucus and tolerability. In the per protocol population absolute inspiratory nasal flow 10 and 20 min after provocation was higher with LQNS compared to placebo (-37 ± 87 mL/s; p = 0.027 and -44 ± 85 mL/s; p = 0.022). The nasal symptom score showed a trend (3.3 ± 1.8 in the placebo and 2.8 ± 1.5 in the LQNS group; p = 0.070) in favor of LQNS; the histamine concentration was not significantly different between the groups. Tolerability of both, LQNS and placebo, was rated as very good. LQNS seems to have an anti-allergic effect in patients with GPA. Copyright © 2016 John Wiley & Sons, Ltd.

Endoscopic retrograde cholangiopancreatography after a liquid fatty meal: effect on deep common bile duct cannulation time.

BACKGROUND AND STUDY AIM: Endoscopic retrograde cholangiopancreatography (ERCP) is an important gastrointestinal endoscopic procedure in the study and treatment of pancreaticobiliary diseases. The critical step of the procedure is cannulation of the common bile duct (CBD) and/or the pancreatic duct. Cannulation can be a technical challenge at times. Fat is a natural stimulator for bile secretion and relaxation of the sphincter of Oddi. The objective of this study was to determine the effect of a liquid fatty meal on deep CBD cannulation during ERCP. PATIENTS AND METHODS: We performed a randomized double-blind study in 84 patients to examine the effect of a liquid fatty meal on deep CBD cannulation during ERCP, in a teaching medical center. In the study group, each patient had a liquid fatty meal orally about 1 hour before the procedure. In the control group, each patient had the same volume of a non-fat meal. The appearance of the major papilla, the cannulation rate, the cannulation time, and the fluoroscopy time during cannulation were compared for the two groups. RESULTS: The orifice of the CBD/pancreatic duct was much more easily identified in the group who ingested the fatty meal. Compared with the non-fat meal group, in the fatty meal group the mean and the median deep CBD cannulation times were shorter, at 8.0 minutes vs. 14.7 minutes ( P = 0.005) and 8.0 minutes vs. 11.5 minutes ( P = 0.008), respectively. Additionally, in the fatty meal group, the mean and the median fluoroscopy times during deep CBD cannulation were lower, at 3.3 minutes vs. 6.1 minutes ( P = 0.040) and 2.5 minutes vs. 3.9 minutes ( P = 0.013), respectively. There were no complications, such as aspiration, associated with the liquid meals given shortly before the ERCP procedure. CONCLUSIONS: To avoid prolonged cannulation and unnecessary radiation exposure, patients should have a liquid fatty meal before ERCP procedures.

Skin protection for photosensitized patients.

BACKGROUND AND OBJECTIVE: The goal of this study was to evaluate various creams for their capability to protect photosensitized skin from visible light. STUDY DESIGN/MATERIALS AND METHODS: Two cover creams and creams containing various combinations of Vaseline with TiO(2), ZnO, and Fe(2)O(3) were used to measure the reduced light transmission and the light absorption spectrum. In vitro and in vivo tests were performed to assess the protection from light by above mentioned compounds. RESULTS: The cover creams and the 50% TiO(2) cream showed similar efficacy in reducing light transmission, while the sunscreen was less efficient by a factor of 5. Cell protection by 25% TiO(2)+25% ZnO, TiO(2), or the cover creams was more efficient than protection by the sunscreen or other compounds. In vivo, the dark cover cream protected the skin by a factor of 3.4 better than the sunscreen. CONCLUSION: The dark cover cream has acceptable properties to protect photosensitized skin.

Low-molecular-weight hyaluronic acid induces nuclear factor-kappaB-dependent resistance against tumor necrosis factor alpha-mediated liver injury in mice.

Liver resident NK1.1+ T cells are supposed to play a pivotal role in the onset of inflammatory liver injury in experimental mouse models such as concanavalin A (Con A)-induced hepatitis. These cells, expressing the adhesion receptor, CD44, are largely depleted from the liver by a single intravenous injection of low-molecular-weight fragments of hyaluronic acid (LMW-HA). Here, we report that LMW-HA pretreatment protected mice from liver injury in several models of T-cell- and macrophage-dependent, tumor necrosis factor alpha (TNF-alpha)-mediated inflammatory liver injury, i.e., from liver injury induced by either Con A or Pseudomonas exotoxin A (PEA) or PEA/lipopolysaccharide (LPS). Interestingly, apart from inhibition of cellular adhesion, pretreatment of mice with LMW-HA was also capable of preventing hepatocellular apoptosis and activation of caspase-3 induced by direct administration of recombinant murine (rmu) TNF-alpha to D-galactosamine (GalN)-sensitized mice. LMW-HA-induced hepatoprotection could be neutralized by pretreatment with the nuclear factor-kappaB (NF-kappaB) inhibitor, pyrrolidine dithiocarbamate (PDTC), demonstrating the involvement of NF-kappaB in the observed protective mechanism. Indeed, injection of LMW-HA rapidly induced the production of TNF-alpha by Kupffer cells and the translocation of NF-kappaB into hepatocellular nuclei. Both LMW-HA-induced TNF-alpha production and NF-kappaB translocation were blocked by pretreatment with PDTC. Our findings provide evidence for an unknown mechanism of LMW-HA-dependent protection from inflammatory liver disease, i.e., induction of TNF-alpha- and NF-kappaB-dependent cytoprotective proteins within the target parenchymal liver cells.

Mitochondrial nitric oxide synthase, oxidative stress and apoptosis.

Nitric oxide (NO) exerts a wide range of its biological properties via its interaction with mitochondria. By competing with O(2), physiologically relevant concentrations of NO reversibly inhibit cytochrome oxidase and decrease O(2) consumption, in a manner resembling a pharmacological competitive antagonism. The inhibition regulates many cellular functions, by e.g., regulating the synthesis of ATP and the formation of mitochondrial transmembrane potential (Delta Psi). NO regulates the oxygen consumption of both the NO-producing and the neighboring cells; thus, it can serve as autoregulator and paracrine modulator of the respiration. On the other hand, NO reacts avidly with superoxide anion (O(2)(-)) to produce the powerful oxidizing agent, peroxynitrite (ONOO(-)) which affects mitochondrial functions mostly in an irreversible manner. How mitochondria and cells harmonize the reversible effects of NO versus the irreversible effects of ONOO(-) will be discussed in this review article. The exciting recent finding of mitochondrial NO synthase will also be discussed.

Animal models for studies on cold-induced platelet activation in human beings.

When human platelets are chilled below about 20 degrees C, they spontaneously activate, a phenomenon that limits their storage lifetime. We have previously shown that this activation in chilled human platelets is associated with passage through a lipid phase transition. Because animal models are necessary for Investigating methods for cold storage of platelets, it is essential to determine whether such phase transitions and chilling-induced activation are found in these models. In this study we examined platelets from some commonly used animal models-pigs, rhesus monkeys, mice, dogs, and rabbits. Using Fourier transform infrared spectroscopy (FTIR), we detected the thermotropic membrane phase transition in Intact platelets and assessed the morphologic response of the platelets to chilling. Statistical analysis of both FTIR and shape change show that of the animal models tested, pig platelets are most similar to human platelets. These studies suggest that pigs and pig platelets are the models of choice for the study of cold-induced platelet activation in human beings.

Effect of ebselen on Ca2+ transport in mitochondria.

The seleno-organic compound ebselen mimics the glutathione-dependent, hydroperoxide reducing activity of glutathione peroxidase. The activity of glutathione peroxidase determines the rate of hydroperoxide-induced Ca2+ release from mitochondria. Ebselen stimulates Ca2+ release from mitochondria, accelerates mitochondrial respiration and uncoupling, and induces mitochondrial swelling, indicating a deterioration of mitochondrial function. These manifestations are abolished by cyclosporine A, a potent inhibitor of the mitochondrial permeability transition. However, when ebselen-induced Ca2+ cycling is prevented with ruthenium red, an inhibitor of the Ca2+ uniporter, or by chelation of extramitochondrial Ca2+ by EGTA, no detectable elevation of swelling or uncoupling is observed. The release of Ca2+ from mitochondria is delayed in the absence of rotenone, i.e. when pyridine nucleotides are maintained in the reduced state due to succinate-driven reversed electron flow. We suggest that ebselen induces Ca2+ release from intact mitochondria via an NAD+ hydrolysis-dependent mechanism.

Mitochondrial nitric-oxide synthase stimulation causes cytochrome c release from isolated mitochondria. Evidence for intramitochondrial peroxynitrite formation.

Nitric oxide (NO) is synthesized by members of the NO synthase (NOS) family. Recently the existence of a mitochondrial NOS (mtNOS), its Ca(2+) dependence, and its relevance for mitochondrial bioenergetics was reported (Ghafourifar, P., and Richter, C. (1997) FEBS Lett. 418, 291-296; Giulivi, C., Poderoso, J. J., and Boveris, A. (1998) J. Biol. Chem. 273, 11038-11043). Here we report on the possible involvement of mtNOS in apoptosis. We show that uptake of Ca(2+) by mitochondria triggers mtNOS activity and causes the release of cytochrome c from isolated mitochondria in a Bcl-2-sensitive manner. mtNOS-induced cytochrome c release was paralleled by increased lipid peroxidation. The release of cytochrome c as well as increase in lipid peroxidation were prevented by NOS inhibitors, a superoxide dismutase mimic, and a peroxynitrite scavenger. We show that mtNOS-induced cytochrome c release is not mediated via the mitochondrial permeability transition pore because the release was aggravated by cyclosporin A and abolished by blockade of mitochondrial calcium uptake by ruthenium red. We conclude that, upon Ca(2+)-induced mtNOS activation, peroxynitrite is formed within mitochondria, which causes the release of cytochrome c from isolated mitochondria, and we propose a mechanism by which elevated Ca(2+) levels induce apoptosis.

Ceramide induces cytochrome c release from isolated mitochondria. Importance of mitochondrial redox state.

In the present study we show that N-acetylsphingosine (C2-ceramide), N-hexanoylsphingosine (C6-ceramide), and, to a much lesser extent, C2-dihydroceramide induce cytochrome c (cyto c) release from isolated rat liver mitochondria. Ceramide-induced cyto c release is prevented by preincubation of mitochondria with a low concentration (40 nM) of Bcl-2. The release takes place when cyto c is oxidized but not when it is reduced. Upon cyto c loss, mitochondrial oxygen consumption, mitochondrial transmembrane potential (Delta Psi), and Ca2+ retention are diminished. Incubation with Bcl-2 prevents, and addition of cyto c reverses the alteration of these mitochondrial functions. In ATP-energized mitochondria, ceramides do not alter Delta Psi, neither when cyto c is oxidized nor when it is reduced, ruling out a nonspecific disturbance by ceramides of mitochondrial membrane integrity. Furthermore, ceramides decrease the reducibility of cyto c. We conclude that the apoptogenic properties of ceramides are in part mediated via their interaction with mitochondrial cyto c followed by its release and that the redox state of cyto c influences its detachment by ceramide from the inner mitochondrial membrane.

Photosensitization of isolated rat liver mitochondria by tetra(m-hydroxyphenyl)chlorin.

Tetra(m-hydroxyphenyl)chlorin (mTHPC) is used as a photosensitizer in photodynamic therapy (PDT), a novel modality for cancer treatment. Since little is known about mTHPC-mediated damage in vitro, we chose isolated rat liver mitochondria as a model system to study its photodynamic effects. Incubation of isolated mitochondria with mTHPC plus irradiation with light of a wavelength of 652 nm resulted in protein oxidation and lipid peroxidation, as measured by the mitochondrial content of carbonyl groups and thiobarbituric acid-reactive substances, respectively. Type I and type II photochemical reactions contribute to this oxidative damage as shown by the use of scavengers. Photodynamically treated mitochondria had a reduced membrane potential, and their Ca2+ uptake was impaired. Oxygen consumption of complex I of the respiratory chain was stimulated at a low concentration of mTHPC plus irradiation, but decreased at higher concentrations, whereas oxygen consumption at complex II and IV decreased with all mTHPC concentrations offered. No mitochondrial changes were seen with mTHPC in the absence of irradiation. Our results confirm the sensitivity of mitochondria to PDT and may help to understand the mechanisms by which PDT using mTHPC kills cells.

Inhibition of the pyridine nucleotide-linked mitochondrial Ca(2+) release by 4-hydroxynonenal: the role of thiolate-disulfide conversion.

Rat liver mitochondria contain a specific Ca(2+) release pathway which operates when intramitochondrial NAD(+) is hydrolyzed to ADPribose and nicotinamide. The molecular details of this pathway are incompletely understood. It has been reported that NAD(+) hydrolysis and therefore Ca(2+) release stimulated by t-butylhydroperoxide is prevented by 4-hydroxynonenal (HNE). The reason underlying inhibition by HNE, however, remained unclear. It has also been reported that NAD(+) hydrolysis and Ca(2+) release are stimulated when some vicinal thiols are cross-linked, as shown with phenylarsine oxide or gliotoxin (GT). We now show that HNE also prevents the GT-induced Ca(2+) release, but only when given before GT. Conversely, GT stimulates Ca(2+) release only when given before HNE. Inhibition of Ca(2+) release by HNE is reduced by its preincubation with thiol compounds, the effectiveness of which increases with decreasing pKa of their sulfhydryl group. Preincubation of HNE with glutathione at high, but not at low, pH similarly reduces inhibition of Ca(2+) release by HNE. These findings provide evidence that HNE inhibition of Ca(2+) release is due to a modification of mitochondrial thiolates in a way that their cross-linking is prevented, and give further insight into the regulation of Ca(2+) release from intact mitochondria.

Delivering bad news: the most challenging task in patient education.

Communicating clinical findings that a patient's vision cannot be improved and/or will deteriorate is a challenging patient education responsibility. The bad news will be upsetting for the patient no matter how it is presented. By presenting findings in a thoughtful, step-by-step manner taking into account the patient's shock and distress and providing appropriate patient education information, the practitioner plays a critical role in facilitating the patient's participation in the rehabilitation process.