Changes In Tissue Concentrations Research Articles

The Fungal Root Endophyte Serendipita indica (Piriformospora indica) Enhances Bread and Durum Wheat Performance under Boron Toxicity at Both Vegetative and Generative Stages of Development through Mechanisms Unrelated to Mineral Homeostasis.

While the importance of beneficial soil microorganisms for soil health and crop performance has been receiving ever-increasing attention, Serendipita indica has been widely studied as a fungal root endophyte with significant potential for increasing the stress tolerance of host plants. Boron (B) toxicity as an adverse soil condition is particularly prevalent in arid and semi-arid regions and threatens crop production. Studies on S. indica-wheat symbiosis are limited, and effects of S. indica on crops have never been reported in the context of B toxicity. Here, two pot experiments were conducted under greenhouse conditions to investigate the effects of S. indica on the growth and yield parameters of bread (Triticum aestivum) and durum wheat (Triticum durum) grown at different levels of B toxicity in native vs. sterilized soil, and parameters related to root colonization, membrane damage, oxidative stress, chlorophyll, and mineral nutrition were measured to elucidate the physiological mechanisms of damage and benefit. Boron toxicity decreased early vegetative growth and grain yield, but it did not affect the straw dry weight of mature plants, whereas S. indica significantly enhanced the vegetative growth, straw dry weight, and the grain number of both wheat species. Membrane damage as demonstrated by increased lipid peroxidation and relative electrolyte leakage was caused by B toxicity and alleviated by S. indica. The benefits provided by S. indica could not be attributed to any significant changes in tissue concentrations of B or other minerals such as phosphorus. Soil sterilization generally improved plant performance but it did not consistently strengthen or weaken the effects of S. indica. The presented results suggest that S. indica may be used as an effective microbial inoculant to enhance wheat growth under adverse soil conditions such as B toxicity through mechanisms that are possibly unrelated to mineral homeostasis.

Special Circumstances of Persons with Dementia and Agitation in Hospice Care.

AbstractBackgroundApproximately 45% of patients with dementia will experience agitation in the last stages of disease. Furthermore, approximately 35% of patients in the late stages of their lives will present agitation despite being treated with lorazepam, morphine, and atypical antipsychotics. Since agitation is particularly prevalent in hospice care, we estimate that at least 45% of the subjects with dementia in hospice care, or approximately 80,000 individuals a year, will die suffering from symptoms of agitation.MethodsDifferences between agitation in dementia at different stages of the disease were evaluated.ResultsAgitation in patients with dementia in the moderate stages of the disease requires the correction of the medical condition that could contribute to the presence of agitation. In hospice care eligible patients with agitation and dementia, these conditions are often untreatable and/or side effects associated with treatment could be more deleterious than the presence of agitation. In the treatment of hospice care eligible patients with agitation and dementia, the main concern is to control symptoms and improve patient’s comfort level while preserving alertness and controlling pain and other symptoms frequently present in terminal patients, including nausea and dyspnea, rather than to uncover and treat the potential underlying cause(s) of the syndrome. In addition, several distinct physiological processes develop both in the CNS and in the periphery during the last few weeks of an individual’s life, including changes in tissue concentrations of glucose, lactate, pyruvate, ATP, ADP, AMP, and phosphocreatine (reflecting brain energy metabolism changes observed during the process of dying and after cardiopulmonary resuscitation).ConclusionSymptoms of agitation in moderate demented patients appear to be biologically and symptomatically different than symptoms of agitation in hospice care eligible patients with dementia. Therefore, the hospice care eligible patients with agitation and dementia need to be better studied and treatments tailored to these specific conditions should be developed.

Transdermal Application of Soluble CuII(atsm) Increases Brain and Spinal Cord Uptake Compared to Gavage with an Insoluble Suspension

CuII(atsm) is a blood–brain barrier permeant copper(II) compound that is under investigation in human clinical trials for the treatment of neurodegenerative diseases of the central nervous system (CNS). Imaging in humans by positron emission tomography shows the compound accumulates in affected regions of the CNS in patients. Most therapeutic studies to date have utilised oral administration of CuII(atsm) in an insoluble form, as either solid tablets or a liquid suspension. However, two pre-clinical studies have demonstrated disease-modifying outcomes following transdermal application of soluble CuII(atsm) prepared in dimethyl sulphoxide. Whether differences in the method of administration lead to different degrees of tissue accumulation of the compound has never been examined. Here, we compare the two methods of administration in wild-type mice by assessing changes in tissue concentrations of copper. Both administration methods resulted in elevated copper concentrations in numerous tissues, with the largest increases evident in the liver, brain and spinal cord. In all instances where treatment with CuII(atsm) resulted in elevated tissue copper, transdermal application of soluble CuII(atsm) led to higher concentrations of copper. In contrast to CuII(atsm), an equivalent dose of copper(II) chloride resulted in minimal changes to tissue copper concentrations, regardless of the administration method. Data presented herein provide quantitative insight to transdermal application of soluble CuII(atsm) as a potential alternative to oral administration of the compound in an insoluble formulation.

Antioxidant tempol modulates the increases in tissue nitric oxide metabolites concentrations after oral nitrite administration

Nitric oxide (NO) metabolites have physiological and pharmacological importance and increasing their tissue concentrations may result in beneficial effects. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) has antioxidant properties that may improve NO bioavailability. Moreover, tempol increases oral nitrite-derived gastric formation of S-nitrosothiols (RSNO). We hypothesized that pretreatment with tempol may further increase tissue concentrations of NO-related species after oral nitrite administration and therefore we carried out a time-dependent analysis of how tempol affects the concentrations of NO metabolites in different tissues after oral nitrite administration to rats. NO metabolites (nitrate, nitrite and RSNO) were assessed by ozone-based reductive chemiluminescence assays in plasma, stomach, aorta, heart and liver samples obtained from anesthetized rats at baseline conditions and 15 min, 30 min, 2 h or 24 h after oral nitrite (15 mg/kg) was administered to rats pretreated with tempol (18 mg/kg) or vehicle 15 min prior to nitrite administration. Aortic protein nitrosation was assessed by resin-assited capture (SNO-RAC) method. We found that pretreatment with tempol transiently enhanced nitrite-induced increases in nitrite, RSNO and nitrate concentrations in the stomach and in the plasma (all P < 0.05), particularly for 15–30 min, without affecting aortic protein nitrosation. Pretreatment with tempol enhanced nitrite-induced increases in nitrite (but not RSNO or nitrate) concentrations in the heart (P < 0.05). In contrast, tempol attenuated nitrite-induced increases in nitrite, RSNO or nitrate concentrations in the liver. These findings show that pretreatment with tempol affects oral nitrite-induced changes in tissue concentrations of NO metabolites depending on tissue type and does not increase nitrite-induced vascular nitrosation. These results may indicate that oral nitrite therapy aiming at achieving increased nitrosation of cardiovascular targets requires appropriate doses of nitrite and is not optimized by tempol.

Role of Transporters in Drug Development.

Role of Transporters in Drug Development.

Multibiomarker response in the earthworm Eisenia fetida as tool for assessing multi-walled carbon nanotube ecotoxicity.

Carbon nanotubes have received a great attention in the last years thanks to their remarkable structural, electrical, and chemical properties. Nowadays carbon nanotubes are increasingly found in terrestrial and aquatic environment and potential harmful impacts of these nanoparticles on humans and wildlife are attracting increasing research and public attention. The effects of carbon nanotubes on aquatic organisms have been explored by several authors, but comparatively the information available on the impact of these particles on soil organisms is much less. Earthworms have traditionally been considered to be convenient indicators of land use impact and soil fertility. The aim of this work was to study the integrated response of a suite of biomarkers covering molecular to whole organism endpoints for the assessment of multi-walled carbon nanotube (MWCNTs) effects on earthworms (Eisenia fetida) exposed to spiked soil. Results showed that cellular and biochemical responses, such as immune cells morphometric alterations and lysosomal membrane destabilization, acetylcholinesterase inhibition and metallothionein tissue concentration changes, showed high sensitivity to MWCNTs exposure. They can improve our understanding and ability to predict chronic toxicity outcomes of MWCNTs exposure such as reproductive alterations. In this context although more investigation is needed to understand the mechanistic pathway relating the biochemical and cellular biomarker analyzed to reproductive alterations, the obtained results give an early contribution to the future development of an adverse outcomes pathways for MWCNTs exposure.

Values of osteoprotegerin in aortic valve tissue in patients with significant aortic stenosis depend on the existence of concomitant coronary artery disease.

Calcific aortic valve stenosis (CAVS) is a serious clinical problem. The strongest predictor of CAVS progression is the amount of calcium in the aortic valve. The pathogenesis of CAVS is largely consistent with the pathogenesis of atherosclerosis; however, about 50% of patients with CAVS do not exhibit significant atherosclerosis. Cardiovascular calcification is currently considered an actively regulated process, in which the important role is attributed to the RANKL/RANK/OPG (receptor activator of nuclear factor κB ligand/RANK/osteoprotegerin) axis. We measured OPG levels in the tissue of calcified, stenotic aortic valves in relation to the presence or absence of coronary artery disease (CAD). Aortic valve samples were collected from 105 patients with calcified, mainly severe aortic stenosis, who were divided into two groups according to the presence of CAD. In Group A (n=44), there were normal coronary artery findings, while in Group B (n=61), there was angiographically demonstrated >50% stenosis of at least one coronary artery. The control Group C (n=21) consisted of patients without aortic stenosis and with normal angiographic findings on coronary arteries. The highest tissue concentrations of OPG [median (pmol/L), 25th-75th percentile] were found in Group A [6.95, 3.96-18.37], which was significantly different compared to the other two groups (P=.026 and .001, respectively). The levels of OPG in Group B [4.15, 2.47-9.16] and in Group C [2.25, 1.01-5.08] did not differ significantly (P=.078); however, the lowest concentrations of OPG were found in Group C. Neither age nor gender in our study had effect on tissue levels of OPG (P=.994 for gender; P=.848 for age). Calcified and narrowed aortic valves, compared to the normal valves, were accompanied by a change in tissue concentrations of OPG, which is, in addition, dependent on the presence or absence of CAD. The highest tissue concentrations of OPG in our work were found in patients with significant aortic stenosis without concomitant CAD.

Hyperspectral optical tomography of intrinsic signals in the rat cortex.

We introduce a tomographic approach for three-dimensional imaging of evoked hemodynamic activity, using broadband illumination and diffuse optical tomography (DOT) image reconstruction. Changes in diffuse reflectance in the rat somatosensory cortex due to stimulation of a single whisker were imaged at a frame rate of 5Hz using a hyperspectral image mapping spectrometer. In each frame, images in 38 wavelength bands from 484 to 652nm were acquired simultaneously. For data analysis, we developed a hyperspectral DOT algorithm that used the Rytov approximation to quantify changes in tissue concentration of oxyhemoglobin ([Formula: see text]) and deoxyhemoglobin (ctHb) in three dimensions. Using this algorithm, the maximum changes in [Formula: see text] and ctHb were found to occur at [Formula: see text] and [Formula: see text] beneath the surface of the cortex, respectively. Rytov tomographic reconstructions revealed maximal spatially localized increases and decreases in [Formula: see text] and ctHb of [Formula: see text] and [Formula: see text], respectively, with these maximum changes occurring at [Formula: see text] poststimulus. The localized optical signals from the Rytov approximation were greater than those from modified Beer-Lambert, likely due in part to the inability of planar reflectance to account for partial volume effects.

Practical Steps for Applying a New Dynamic Model to Near-Infrared Spectroscopy Measurements of Hemodynamic Oscillations and Transient Changes: Implications for Cerebrovascular and Functional Brain Studies

Perturbations in cerebral blood volume (CBV), blood flow (CBF), and metabolic rate of oxygen (CMRO2) lead to associated changes in tissue concentrations of oxy- and deoxy-hemoglobin (ΔO and ΔD), which can be measured by near-infrared spectroscopy (NIRS). A novel hemodynamic model has been introduced to relate physiological perturbations and measured quantities. We seek to use this model to determine functional traces of cbv(t) and cbf(t) - cmro2(t) from time-varying NIRS data, and cerebrovascular physiological parameters from oscillatory NIRS data (lowercase letters denote the relative changes in CBV, CBF, and CMRO2 with respect to baseline). Such a practical implementation of a quantitative hemodynamic model is an important step toward the clinical translation of NIRS. In the time domain, we have simulated O(t) and D(t) traces induced by cerebral activation. In the frequency domain, we have performed a new analysis of frequency-resolved measurements of cerebral hemodynamic oscillations during a paced breathing paradigm. We have demonstrated that cbv(t) and cbf(t) - cmro2(t) can be reliably obtained from O(t) and D(t) using the model, and that the functional NIRS signals are delayed with respect to cbf(t) - cmro2(t) as a result of the blood transit time in the microvasculature. In the frequency domain, we have identified physiological parameters (e.g., blood transit time, cutoff frequency of autoregulation) that can be measured by frequency-resolved measurements of hemodynamic oscillations. The ability to perform noninvasive measurements of cerebrovascular parameters has far-reaching clinical implications. Functional brain studies rely on measurements of CBV, CBF, and CMRO2, whereas the diagnosis and assessment of neurovascular disorders, traumatic brain injury, and stroke would benefit from measurements of local cerebral hemodynamics and autoregulation.

Effect of training and vitamin E administration on rat liver oxidative metabolism

We studied vitamin E effects on metabolic changes and oxidative damage elicited by swim training in rat liver. Training reduced mitochondrial aerobic capacity but increased liver content of mitochondrial proteins, so that tissue aerobic capacity was not different in trained and sedentary animals. Vitamin E supplementation prevented the training-induced mitochondrial changes. Training and vitamin E effects were consistent with the changes in tissue content of factors involved in mitochondrial biogenesis (peroxisomal proliferator-activated receptor-γ coactivator and nuclear respiratory factors 1 and 2).Tissue and mitochondrial oxidative damage was reduced by training decreasing the rate of mitochondrial reactive oxygen species (ROS) production and enhancing glutathione levels and glutathione peroxidase and glutathione reductase activities. The effects of vitamin E were different when it was administered to sedentary or trained rats. In the former, vitamin E reduced liver preparations oxidative damage decreasing ROS production rate and increasing GSH content without any effect on antioxidant enzyme activities. In the latter, vitamin E did not modify ROS production and oxidative damage but decreased antioxidant levels. This decrease was likely responsible for the enhanced susceptibility to in vitro oxidative attack of the hepatic tissue from trained rats following vitamin E supplementation. These results indicate that vitamin E integration, which can be healthy for animals subjected to acute exercise, is not advisable during training because it prevents or reduces the favourable effects of the physical activity. They also support the idea that the stimulus for training-induced adaptive responses can derive from the increased ROS production that accompanies the single sessions of the training program.

Oxidative stress and changes in the content and pattern of tissue expression of &amp;#946;-catenin protein in diversion colitis

OBJECTIVE: The aim of this study is to verify if oxidative stress is related to changes in content and pattern of β-catenin protein expression in an experimental model of diversion colitis. METHODS: Sixty Wistar rats were submitted to intestinal bypass. The animals were divided into three groups according to the sacrifice to take place in six, 12 and 18 weeks. For each group, five animals only underwent laparotomy (control). The presence of colitis was diagnosed by histological study, and its severity, by inflammation grading scale. Cellular oxidative stress was measured by comet assay. Tissue expression of β-catenin protein was analyzed by the immunohistochemistry and quantification of its tissue content by computerized morphometry. Statistical analysis was performed with the Student's t-test, median, Mann-Whitney, ANOVA and Kruskal-Wallis, adopting a significance level of 5% (p <0.05). RESULTS: Colon segments without fecal stream developed colitis, which worsened with time of exclusion. Segments without fecal stream suffer higher levels of oxidative stress when compared to those with stream, and it worsens with time of exclusion. The levels of cellular oxidative stress are directly related to the degree of inflammation. The total content of β-catenin in segments without fecal stream reduces after six weeks, and does not vary thereafter. The content of β-catenin in the apical portion of the colon crypts decreases with time, whereas in the basal region, it increases. The total content of β-catenin is inversely related to the degree of inflammation and levels of tissue oxidative stress levels. CONCLUSION: There are changes in tissue content of E-cadherin and increased expression of β-catenin in proliferative regions of colonic crypts, related with oxidative tissue stress.

Structural brain changes linked to delayed first language acquisition in congenitally deaf individuals

Early language experience is essential for the development of a high level of linguistic proficiency in adulthood and in a recent functional Magnetic Resonance Imaging (fMRI) experiment, we showed that a delayed acquisition of a first language results in changes in the functional organization of the adult brain (Mayberry et al., 2011). The present study extends the question to explore if delayed acquisition of a first language also modulates the structural development of the brain. To this end, we carried out anatomical MRI in the same group of congenitally deaf individuals who varied in the age of acquisition of a first language, American Sign Language -ASL (Mayberry et al., 2011) and used a neuroanatomical technique, Voxel-Based Morphometry (VBM), to explore changes in gray and white matter concentrations across the brain related to the age of first language acquisition. The results show that delayed acquisition of a first language is associated with changes in tissue concentration in the occipital cortex close to the area that has been found to show functional recruitment during language processing in these deaf individuals with a late age of acquisition. These findings suggest that a lack of early language experience affects not only the functional but also the anatomical organization of the brain.

The interactive effects of selenomethionine and methylmercury on their absorption, disposition, and elimination in juvenile white sturgeon

Selenium (Se) and mercury (Hg) are prevalent pollutants of industrialized watersheds. However, when co-administered, Se has protective effects on organisms from Hg. The mechanism is not fully understood, but it is thought that Se reduces Hg availability, either by forming biologically inert complexes and/or associating with selenoproteins. Despite concerns with aquatic contaminations, relatively little information is available on the interaction in aquatic organisms. In the present study, the interactive effects of Se and Hg on their absorption, disposition, and elimination were examined in juvenile white sturgeon, a benthic fish species at high risk to exposures of both contaminants. Selenium and Hg were provided as l-selenomethionine (SeMet) and methylmercury (MeHg), respectively. Groups of 10 sturgeon were orally intubated with a single dose of either 0 (control), SeMet (500μg Se/kg body weight; BW), MeHg (850μg Hg/kg BW), or their combination (Se/Hg; 500μg Se/kg and 850μg Hg/kg BW). The blood was repeatedly sampled and urine collected from the fish, over a 48h post intubation period. At 48h, the fish were sacrificed for Se and Hg tissue concentration and distribution. The co-administration of SeMet and MeHg significantly (p<0.05) lowered blood concentrations of both Se and Hg and tissue Se concentrations. Similarly, assimilation of Se and Hg was also reduced significantly. The interaction has a more quantitative effect on Se metabolism because the reduction in the overall tissue Se is a consequence of reduced Se absorption at the gut and not from the metabolic effects after absorption. In contrast, given the pulse increase in blood Hg concentration, tissue redistribution, and increased urinary elimination, the interactive effect on tissue Hg concentration is likely to be post-absorption. Even in the absence of exogenous SeMet, Se and Hg co-accumulated in tissue at a Se:Hg molar ratio greater than 1. Thus, similar to mammals, maintaining at least a 1:1 molar ratio of Se and Hg is of great physiological importance in the white sturgeon. Interestingly, SeMet did not divert Hg from the brain. Allocation of Se from the kidneys may have occurred in order to maintain the high Se:Hg molar ratios in the brain of white sturgeon. In the current study, the combined use of kinetic analysis and that of the conventional approach of measuring tissue concentration changes provided a comprehensive understanding of the interactive effect of SeMet and MeHg on their respective metabolic processes in juvenile white sturgeon.

Changes in trace elements during lactation in a marine top predator, the grey seal

Lactation in pinnipeds represents the most significant cost to mothers during the reproductive cycle. Dynamics of trace elements and their mobilization associated with energy reserves during such an intense physiological process remains poorly understood in marine mammals. The changes in tissue concentrations of 11 elements (Ca, Cd, Cr, Cu, Fe, Hg, Ni, Pb, Se, V, and Zn) were investigated in a longitudinal study during the lactation period and during the post-weaning fast period. Blood, milk, blubber, and hair samples were collected sequentially from 21 mother–pup pairs of grey seals (Halichoerus grypus) from the Isle of May in Scotland. Maternal transfer through the milk was observed for all trace elements, except for Cd. As an indicator of the placental transfer, levels in pup lanugo (natal coat) revealed also the existence of maternal transfer and accumulation of all assayed trace elements during the foetal development. The placental and mammary barriers against non-essential metal transfer to offspring appear to be absent or weak in grey seals. Examining the contamination levels showed that this grey seal population seems more highly exposed to Pb than other phocid populations (2.2mg/kg dw of grey seal hair). In contrast, blood and hair levels reflected a lower Hg exposure in grey seals from the Isle of May than in harbour seals from the southeastern North Sea. This study also showed that trace element concentrations in blood and blubber could change rapidly over the lactation period. Such physiological processes must be considered carefully during biomonitoring of trace elements, and potential impacts that rapid fluctuations in concentrations can exert on seal health should be further investigated.

Effects of exposure to amphetamine derivatives on passive avoidance performance and the central levels of monoamines and their metabolites in mice: Correlations between behavior and neurochemistry

Considerable evidence indicates that amphetamine derivatives can deplete brain monoaminergic neurotransmitters. However, the behavioral and cognitive consequences of neurochemical depletions induced by amphetamines are not well established. In this study, mice were exposed to dosing regimens of 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (METH), or parachloroamphetamine (PCA) known to deplete the monoamine neurotransmitters dopamine and serotonin, and the effects of these dosing regimens on learning and memory were assessed. In the same animals, we determined deficits in learning and memory via passive avoidance (PA) behavior and changes in tissue content of monoamine neurotransmitters and their primary metabolites in the striatum, frontal cortex, cingulate, hippocampus, and amygdala via ex vivo high-pressure liquid chromatography. Exposure to METH and PCA impaired PA performance and resulted in significant depletions of dopamine, serotonin, and their metabolites in several brain regions. Multiple linear regression analysis revealed that the tissue concentration of dopamine in the anterior striatum was the strongest predictor of PA performance, with an additional significant contribution by the tissue concentration of the serotonin metabolite 5-hydroxyindoleacetic acid in the cingulate. In contrast to the effects of METH and PCA, exposure to MDMA did not deplete anterior striatal dopamine levels or cingulate levels of 5-hydroxyindoleacetic acid, and it did not impair PA performance. These studies demonstrate that certain amphetamines impair PA performance in mice and that these impairments may be attributable to specific neurochemical depletions.

BOLD imaging: a potential predictive biomarker of renal functional outcome following revascularization in atheromatous renovascular disease

Stenting of the stenosed renal artery is commonly employed in atheromatous renovascular disease (ARVD) in order to revascularize the affected kidney. However, it is still far from clear which patient subgroups should be revascularized as stenting carries small but significant risks. We have previously demonstrated that the ratio of magnetic resonance-measured renal volume to isotopic single kidney glomerular filtration rate (isoSK-GFR) is higher in kidneys which show functional improvement after revascularization. Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) does not require contrast administration and is sensitive to changes in tissue concentration of deoxyhaemoglobin. In this study, we test the hypothesis that baseline BOLD R2* map signal and R2*:isoSK-GFR ratio will provide an additional independent predictive biomarker of response to revascularization. Studies were performed in 28 subjects (16 ARVD and 12 controls). All subjects had R2* mapping and isoSK-GFR measured at baseline and at 4-month follow-up. MRI data were collected on a 3 T whole-body MRI scanner using a coronal dual-echo, 2D gradient-echo breath-hold acquisition. Parenchymal regions of interest (ROIs) were drawn on a representative slice through the middle of the kidney. Parametric maps of R2* were generated and mean values of R2* were calculated for every ROI. The ratio of R2*:isoSK-GFR at baseline was significantly greater in kidneys where renal function improved (5.91 ± 6.51) versus stable (1.78 ± 1.11), deteriorated (2.15 ± 1.79) or controls (1.5 ± 0.91), P = 0.003. R2*:isoSK-GFR ratio that was greater than 95% confidence interval of the control kidneys was 66.7% sensitive, but 85.7% specific in predicting a positive renal functional outcome. These pilot data show that BOLD R2* imaging, presumably by detecting intra-renal deoxyhaemoglobin in still viable 'hibernating' parenchyma, coupled with isoSK-GFR may provide an effective predictive biomarker for positive renal functional response to revascularization. R2* imaging is non-invasive, quick to perform and could provide further insight into reversible parenchymal changes in ARVD kidneys.

Carvedilol Induces Endogenous Hydrogen Sulfide Tissue Concentration Changes in Various Mouse Organs

Carvedilol, a third generation non-selective adrenoreceptor blocker, is widely used in cardiology. Its action has been proven to reach beyond adrenergic antagonism and involves multiple biological mechanisms. The interaction between carvedilol and endogenous 'gasotransmitter' hydrogen sulfide (H2S) is unknown. The aim of the study is to assess the influence of carvedilol on the H2S tissue level in mouse brain, liver, heart and kidney. Twenty eight SJL strain female mice were administered intraperitoneal injections of 2.5 mg/kg b.w./d (group D1, n=7), 5 mg/kg b.w./d (group D2, n=7) or 10 mg/kg b.w./d of carvedilol (group D3, n=7). The control group (n=7) received physiological saline in portions of the same volume (0.2 ml). Measurements of the free tissue H2S concentrations were performed according to the modified method of Siegel. A progressive decline in H2S tissue concentration along with an increase in carvedilol dose was observed in the brain (12.5%, 13.7% and 19.6%, respectively). Only the highest carvedilol dose induced a change in H2S tissue level in the heart - an increase by 75.5%. In the liver medium and high doses of carvedilol increased the H2S level by 48.1% and 11.8%, respectively. In the kidney, group D2 showed a significant decrease of H2S tissue level (22.5%), while in the D3 group the H2S concentration increased by 12.9%. Our study has proven that carvedilol affects H2S tissue concentration in different mouse organs.

Tissue concentration changes of amino acids and biogenic amines in the central nervous system of mice with experimental autoimmune encephalomyelitis (EAE)

We have characterized the changes in tissue concentrations of amino acids and biogenic amines in the central nervous system (CNS) of mice with MOG 35–55-induced experimental autoimmune encephalomyelitis (EAE), an animal model commonly used to study multiple sclerosis (MS). High performance liquid chromatography was used to analyse tissue samples from five regions of the CNS at the onset, peak and chronic phase of MOG 35–55 EAE. Our analysis includes the evaluation of several newly examined amino acids including d-serine, and the inter-relations between the intraspinal concentration changes of different amino acids and biogenic amines during EAE. Our results confirm many of the findings from similar studies using different variants of the EAE model as well as those examining changes in amino acid and biogenic amine levels in the cerebrospinal fluid (CSF) of MS patients. However, several notable differences were observed between mice with MOG 35–55-induced EAE with findings from human studies and other EAE models. In addition, our analysis has identified strong correlations between different amino acids and biogenic amines that appear to change in two distinct groups during EAE. Group I analyte concentrations are increased at EAE onset and peak but then decrease in the chronic phase with a large degree of variability. Group II is composed of amino acids and biogenic amines that change in a progressive manner during EAE. The altered levels of these amino acids and biogenic amines in the disease may represent a critical pathway leading to neurodegenerative processes that are now recognized to occur in EAE and MS.

Uric acid deposits and estivation in the invasive apple-snail, Pomacea canaliculata

The physiological ability to estivate is relevant for the maintenance of population size in the invasive Pomacea canaliculata. However, tissue reoxygenation during arousal from estivation poses the problem of acute oxidative stress. Uric acid is a potent antioxidant in several systems and it is stored in specialized tissues of P. canaliculata. Changes in tissue concentration of thiobarbituric acid reactive substances (TBARS), uric acid and allantoin were measured during estivation and arousal in P. canaliculata. Both TBARS and uric acid increased two-fold during 45days estivation, probably as a consequence of concomitant oxyradical production during uric acid synthesis by xanthine oxidase. However, after arousal was induced, uric acid and TBARS dropped to or near baseline levels within 20min and remained low up to 24h after arousal induction, while the urate oxidation product allantoin continuously rose to a maximum at 24h after induction, indicating the participation of uric acid as an antioxidant during reoxygenation. Neither uric acid nor allantoin was detected in the excreta during this 24h period. Urate oxidase activity was also found in organs of active snails, but activity shut down during estivation and only a partial and sustained recovery was observed in the midgut gland.

Anticonvulsive effect of vitamin C on pentylenetetrazol-induced seizures in immature rats

Vitamin C helps to prevent brain oxidative stress and participate in the synthesis of progesterone. It also possesses a progesterone-like effect and acts synergistically with progesterone on the brain. Progesterone and its metabolites, but also vitamin C have been associated with anticonvulsant effects. We evaluated the progesterone concentration 30 min and 24 h after the last administration of vitamin C (500 mg/kg, i.p. for five days). We also evaluated how vitamin C altered pentylenetetrazol (PTZ)-induced seizures by measuring the onset latency of seizures, percentage of incidence and mortality as well as amino acid levels after seizures. Vitamin C treatment alone increased basal progesterone concentrations to 531% after 30 min compared to 253% after 24 h. Furthermore, vitamin C significantly increased the latency to the first myoclonic, clonic and tonic seizure induced by PTZ (80 mg/kg, i.p.) and decreased the percentage of incidence of clonic and tonic seizures as well as the mortality rate. Changes in tissue concentration of amino acids were primarily observed at 24 h after vitamin C treatment. Our results suggest that vitamin C together with progesterone and/or its metabolites are involved in the protection against PTZ-induced seizures in immature rats.