21,390 research outputs found
Cellular protection from oxidative stress by the blood orange pigment cyanidin-3-O-beta-glucopyranoside
No full textThe cyanidin-3-O--glucopyranoside (C-3-G) antioxidant effects were assessed in two models of increased oxidative stress. Isolated post-ischemic rat heart reperfused with C-3-G showed inhibition of malondialdehyde (MDA) formation (-67% and -94% in 10 and 30 M C-3-G-reperfused hearts, respectively) and improved energy metabolism. Normoxic hearts perfused in the recirculating Langendorff mode with 10 and 30 M C-3-G indicated that C-3-G can permeate within myocardial cells. Dose-dependent decrease of MDA generation by C-3-G was observed in 2 mM H2O2-treated human erythrocytes (apparent IC50 of 5.12 M and 38.43 M were calculated for C-3-G and resveratrol, respectively). In conclusion, C-3-G (largely present also in pigmented oranges) may have beneficial effects in case of increased oxidative stress
Hypothesis of the postconcussive vulnerable brain: experimental evidence of its metabolic occurrence
No full textOBJECTIVE: We evaluated the effects of two consecutive concussive injuries on brain energy metabolism and N-acetylaspartate (NAA) to investigate how the temporal interval between traumatic events influences overall injury severity. METHODS: Rats were injured to induce diffuse traumatic brain injury (TBI) (mild, 450 g/1 m; severe, 450 g/2 m). In two groups, two mild TBIs were delivered in 3- or 5-day intervals. Three additional animal groups were used: single mild TBI, single severe TBI, and sham. All animals were killed 48 hours postinjury. Adenosine 5'-triphosphate (ATP), adenosine diphosphate, and NAA concentrations were analyzed with high-performance liquid chromatography on deproteinized whole brain extracts. RESULTS: In control animals, the NAA concentration was 9.17 +/- 0.38 micromol/g wet weight, the ATP concentration was 2.25 +/- 0.21 micromol/g wet weight, and the ATP-to-adenosine diphosphate ratio was 9.38 +/- 1.23. These concentrations decreased to 6.68 +/- 1.12 micromol/g wet weight, 1.68 +/- 0.24 micromol/g wet weight, and 6.10 +/- 1.21 micromol/g wet weight, respectively, in rats that received two mild TBIs at a 5-day interval (P 0.01; not different from results in rats with single mild TBI). When a second TBI was delivered after 3 days, the NAA concentration was 3.86 +/- 0.53 micromol/g wet weight, the ATP concentration was 1.11 +/- 0.18 micromol/g wet weight, and the ATP-to-adenosine diphosphate ratio was 2.64 +/- 0.43 (P 0.001 versus both controls and 3-day interval; not different from rats receiving a single severe TBI). CONCLUSION: The biochemical modification severity in double TBI is dependent on the interval between traumatic events, which demonstrates the metabolic state of the vulnerable brain after mild TBI. These data support the hypothesis of the application of proton magnetic resonance spectroscopy to measure NAA as a possible tool to monitor the full recovery of brain metabolic functions in the clinical setting, particularly in sports medicine
Cerebral oxidative stress and depression of energy metabolism correlate with severity of diffuse brain injury in rats.
No full textOBJECTIVE:
The combined effect of traumatic brain injury (TBI) and secondary insult on biochemical changes of cerebral tissue is not well known. For this purpose, we studied the time-course changes of parameters reflecting ROS-mediated oxidative stress and modifications of cell energy metabolism determined in rats subjected to cerebral insult of increasing severity.
METHODS:
Rats were divided into four groups: 1) sham-operated, 2) subjected to 10 minutes of hypoxia and hypotension (HH), 3) subjected to severe diffuse TBI, and 4) subjected to severe diffuse TBI + HH. Rats were killed at different times after injury, and analyses of malondialdehyde, ascorbate, high-energy phosphates, nicotinic coenzymes, oxypurines, nucleosides, and N-acetylaspartate (NAA) were made by high-performance liquid chromatography on whole-brain tissue extracts.
RESULTS:
Data indicated a close relationship between degree of oxidative stress and severity of brain insult, as evidenced by the highest malondialdehyde values and lowest ascorbate levels in rats subjected to TBI + HH. Similarly, modifications of parameters related to cell energy metabolism were modulated by increasing severity of brain injury, as demonstrated by the lowest values of energy charge potential, nicotinic coenzymes, and NAA and the highest levels of oxypurines and nucleosides recorded in TBI + HH rats. Both the intensity of oxidative stress-mediated cerebral damage and perturbation of energy metabolism were minimally affected in rats subjected to HH only.
CONCLUSION:
These results showed that the severity of brain insult can be graded by measuring biochemical modifications, specifically, reactive oxygen species-mediated damage, energy metabolism depression, and NAA, thereby validating the rodent model of closed-head diffuse TBI coupled with HH and proposing NAA as a marker with diagnostic relevance to monitor the metabolic state of postinjured brain
Protecting Animals 36: Author Witi Ihimaera
No full textIn this very special episode of Knowing Animals I am joined by beloved New Zealand author Witi Ihimaera. Witi has written many books featuring nonhuman animals. He offers us a non-colonial lens through which to think about the human/nonhuman relationship
Chromosomal 17p13.3 microdeletion unmasking recessive Canavan disease mutation
No full textUnmasking a recessive allele on one chromosome by a deletion on the other is a disease causing mechanism often invoked but rarely proven. We report on an Italian female patient with Canavan disease (OMIM# 271900) due to a missense mutation of the aspartoacylase (ASPA) gene and a 17p13.3 chromosomal microdeletion
I Think I Am Philip K. Dick
No full textFor years, noted writer Laurence A. Rickels often found himself compared to novelist Philip K. Dickthough in fact Rickels had never read any of the science fiction writers work. When he finally read his first Philip K. Dick novel, while researching for his recent book The Devil Notebooks , it prompted a prolonged immersion in Dicks writing as well as a recognition of Rickelss own long-documented intellectual pursuits. The result of this engagement is I Think I Am: Philip K. Dick , a profound thought experiment that charts the wide relevance of the pulp sci-fi author and paranoid visionary. I Think I Am: Philip K. Dick explores the science fiction authors meditations on psychic reality and psychosis, Christian mysticism, Eastern religion, and modern spiritualism. Covering all of Dicks science fiction, Rickels corrects the lack of scholarly interest in the legendary Californian author and, ultimately, makes a compelling case for the philosophical and psychoanalytic significance of Philip K. Dicks popular and influential science fiction.Intro -- Contents -- Introjection -- Part I -- Endopsychic Allegories -- Schreber Guardian -- Belief System Surveillance -- Part II -- Deeper Problems -- Veil of Tears -- Go West -- Dick Manfred -- Timing -- Glimmung -- Part III -- Spiritualism Analogy -- Imitating the Dead -- Indexical Layer -- Ilse -- Hammers and Things -- Crucifictions -- Over There -- Martyrology -- Can't Live, Can't Live -- Lola -- Umwelt, Mitwelt, and Eigenwelt -- Outer Race -- The German Introject -- Part IV -- Materialism, Idealism, and Cybernetics -- Startling Stories -- A Couple of Years -- Android Empathy -- Homunculus and Robot -- ALL OF YOU ARE DEAD. I AM ALIVE. -- Go with the Flow -- Part V -- Room for Thought -- Caduceus -- Jump -- Still -- A Wake -- Spätwerk -- Let the Dead Be -- Play Bally -- Das Hund -- Notes -- BibliographyFor years, noted writer Laurence A. Rickels often found himself compared to novelist Philip K. Dickthough in fact Rickels had never read any of the science fiction writers work. When he finally read his first Philip K. Dick novel, while researching for his recent book The Devil Notebooks , it prompted a prolonged immersion in Dicks writing as well as a recognition of Rickelss own long-documented intellectual pursuits. The result of this engagement is I Think I Am: Philip K. Dick , a profound thought experiment that charts the wide relevance of the pulp sci-fi author and paranoid visionary. I Think I Am: Philip K. Dick explores the science fiction authors meditations on psychic reality and psychosis, Christian mysticism, Eastern religion, and modern spiritualism. Covering all of Dicks science fiction, Rickels corrects the lack of scholarly interest in the legendary Californian author and, ultimately, makes a compelling case for the philosophical and psychoanalytic significance of Philip K. Dicks popular and influential science fiction.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
The protective effect of Cyclosporin A upon N-acetylaspartate and mitochondrial dysfunction following experimental diffuse traumatic brain injury
No full textPre- and post-injury Cyclosporin A (CsA) administration has shown neuroprotective properties by ameliorating mitochondrial damage. The aim of this study was to assess the effect of CsA upon N-acetylaspartate (NAA) reduction and ATP loss, two sensitive markers of mitochondrial dysfunction and bioenergetic impairment. Adult male Sprague-Dawley rats were exposed to impact acceleration traumatic brain injury (2 m/450 g) and randomized into the following experimental groups: intrathecal CsA/vehicle treated (n = 12), intravenous CsA/vehicle treated (n = 18) and sham (n = 12). Intrathecal treatment consisted of post-injury (30 min) cisternal bolus of CsA or Vehicle (0.15 mL, 10 mg/kg). Intravenous administration consisted of 30 min post-injury continuous 1hour infusion of either 20 or 35 mg/kg CsA or Vehicle. Quantitative HPLC analysis of whole brain samples was performed 6 h post-injury for levels of NAA and ATP. Following intrathecal delivery CsA demonstrated significant neuroprotection blunting a 30% NAA reduction (p < 0.001) and restoring 26% of the ATP loss (p < 0.005). The 20 mg/kg intravenous dose failed to ameliorate the biochemical damages while the 35 mg/kg dosage showed 36% NAA recovery and 39% ATP restoration (p < 0.001). In conclusion, CsA is capable of restoring ATP and blunting NAA reduction. Intravenous infusion of 35 mg/kg appears to be the optimal therapeutic strategy in this model. These findings contribute to the notion that CsA achieves neuroprotection, preserving mitochondrial function, and provides a rationale for the assessment of CsA in the clinical setting where MR spectroscopy can monitor NAA and ATP in brain-injured patients
Biochemical analysis of the cerebrospinal fluid: evidence for catastrophic energy failure and oxidative damage preceding brain death in severe head injury: a case report
No full textObjectives: To compare biochemical and clinical parameters in a case of fatal severe traumatic brain injury (TBI) with secondary insult. Design and methods: A TBI patient was catheterized for intracranial pressure (ICP) monitoring and cerebrospinal fluid (CSF) analysis of ascorbate, malondialdehyde, oxypurines, and nucleosides. Results: Oxidative brain damage preceded ATP catabolite increment in the CSF even with ICP below 20 mm Hg. Sustained oxidative stress caused irreversible energy state derangement followed by a refractory ICP rise. Massive oxypurine and nucleoside release was recorded 36 h before brain death. Conclusions: Molecular events, detected by biochemical CSF analysis and preceding modification of clinical parameters in severe TBI with secondary insult, are discussed. (C) 2004 The Canadian Society of Clinical Chemists. All rights reserved
Hypothesis of the postconcussive vulnerable brain: Experimental evidence of its metabolic occurrence
No full textOBJECTIVE: We evaluated the effects of two consecutive concussive injuries on brain energy metabolism and N-acetylaspartate (NAA) to investigate how the temporal interval between traumatic events influences overall injury severity. METHODS: Rats were injured to induce diffuse traumatic brain injury (TBI) (mild, 450 g/1 m; severe, 450 g/2 m). In two groups, two mild TBIs were delivered in 3- or 5-day intervals. Three additional animal groups were used: single mild TBI, single severe TBI, and sham. All animals were killed 48 hours postinjury. Adenosine 5'-triphosphate (ATP), adenosine diphosphate, and NAA concentrations were analyzed with high-performance liquid chromatography on deproteinized whole brain extracts. RESULTS: In control animals, the NAA concentration was 9.17 +/- 0.38 mu mol/g wet weight, the ATP concentration was 2.25 +/- 0.21 mu mol/g wet weight, and the ATP-to-adenosine diphosphate ratio was 9.38 +/- 1.23. These concentrations decreased to 6.68 +/- 1.12 mu mol/g wet weight, 1.68 +/- 0.24 mu mol/g wet weight, and 6.10 +/- 1.21 mu mol/g wet weight, respectively, in rats that received two mild TBIs at a 5-day interval (P < 0.01; not different from results in rats with single mild TBI). When a second TBI was delivered after 3 days, the NAA concentration was 3.86 +/- 0.53 mu mol/g wet weight, the ATP concentration was 1.11 +/- 0.18 mu mol/g wet weight, and the ATP-to-adenosine diphosphate ratio was 2.64 +/- 0.43 (P < 0.001 versus both controls and 3-day interval; not different from rats receiving a single severe TBI). CONCLUSION: The biochemical modification severity in double TBI is dependent on the interval between traumatic events, which demonstrates the metabolic state of the vulnerable brain after mild TBI. These data support the hypothesis of the application of proton magnetic resonance spectroscopy to measure NAA as a possible tool to monitor the full recovery of brain metabolic functions in the clinical setting, particularly in sports medicine
Low-molecular weight compounds in human seminal plasma as potential biomarkers of male infertility
No full textSTUDY QUESTION: Is the determination of antioxidants, oxidative/nitrosative stress-related compounds, purines, pyrimidines and energy-related metabolites in human seminal plasma of utility to evidence biomarkers related to male infertility? SUMMARY ANSWER: The determination of 26 metabolites in seminal plasma allowed to evidence that 21/26 of them are biomarkers of male infertility, as well as to calculate a cumulative index, named Biomarker Score, that fully discriminates fertile controls from infertile patients and partially differentiates infertile without from infertile with spermiogram anomalies. WHAT IS KNOWN ALREADY: Epidemiological studies indicated that a male factor is involved in ∼50% of cases of pregnancy failure, with a significant percentage of infertile males having no alterations in the spermiogram. Further laboratory analyses of male infertility are mainly dedicated only to gross evaluations of oxidative stress or total antioxidant capacity. STUDY DESIGN, SIZE, DURATION: Seminal plasma of 48 fertile controls and 96 infertile patients (master group), were collected from September 2016 to February 2018. A second group of 44 infertile patients (validation group) was recruited in a second, independent centre from September 2017 to March 2018. Samples were analysed in blind using a 'Redox Energy Test' to determine various low-molecular weight compounds, with the aim of finding metabolic profiles and biomarkers related to male infertility. PARTICIPANTS/MATERIALS, SETTING, METHODS: In all seminal plasma, 26 water- and fat-soluble compounds (related to antioxidant defences, oxidative/nitrosative stress, purine, pyrimidine and energy metabolism) were analysed using high-performance liquid chromatographic methods. According to spermiogram, infertile patients of both groups were also categorized into normozoospermic (N, no anomalies in the spermiogram), or into the subgroup including all patients with anomalies in the spermiogram (asthenoteratooligozoospermic ATO + asthenozoospermic A + teratozoospermic T + oligozoospermic O). MAIN RESULTS AND THE ROLE OF CHANCE: In the master group, results indicated that 21/26 compounds assayed in seminal plasma of infertile males were significantly different from corresponding values determined in fertile controls. These 21 compounds constituted the male infertility biomarkers. Similar results were recorded in patients of the validation group. Using an index cumulating the biochemical seminal plasma anomalies (Biomarker Score), we found that fertile controls had mean Biomarker Score values of 2.01 ± 1.42, whilst infertile patients of the master and of the validation group had mean values of 12.27 ± 3.15 and of 11.41 ± 4.09, respectively (P < 0.001 compared to controls). The lack of statistical differences between the master and the validation groups, in both the metabolic profiles and the Biomarker Score values, allowed to pool patients into a single cohort of infertile males. The Biomarker Score values showed that fertile controls and infertile males clustered into two distinct groups. Infertile patients without (N, n = 42) or with (ATO + A + T + O, n = 98) spermiogram anomalies differed in some biomarkers (ascorbic acid, all-trans retinol, α-tocopherol, cytidine, uridine, guanine). These differences were reinforced by distribution frequencies and posterior probability curves of the Biomarker Score in the three groups. LIMITATIONS, REASONS FOR CAUTION: Results were obtained in relatively limited number of human seminal plasma samples. Using the 'Redox Energy Test' it was possible to associate specific metabolic profiles and values of the Biomarker Score to fertile controls or infertile males. However, it was not possible to evaluate whether the different anomalies of the spermiogram are associated with specific metabolic profiles and values of the Biomarker Score. WIDER IMPLICATIONS OF THE FINDINGS: The 'Redox Energy Test', coupled with the Biomarker Score that cumulates the biochemical characteristics of seminal plasma into a single index, evidenced a set of low-molecular weight biomarkers potentially useful in the laboratory management of male infertilit
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