Publications by authors named "Paul Donohoe"

15 Publications

  • Page 1 of 1

Volatile Organic Compounds as Insect Repellents and Plant Elicitors: an Integrated Pest Management (IPM) Strategy for Glasshouse Whitefly (Trialeurodes vaporariorum).

J Chem Ecol 2020 Dec 27;46(11-12):1090-1104. Epub 2020 Oct 27.

School of Natural and Environmental Sciences, Newcastle University, Newcastle-upon-Tyne, NE1 7RU, UK.

The glasshouse whitefly (Trialeurodes vaporariorum Westwood) is a polyphagous arthropod pest that is of particular detriment to glasshouse grown tomato (Solanum lycopersicum) across temperate regions of the world. Control of whiteflies with synthetic pesticides has resulted in the evolution of resistant genotypes and a reduction in natural enemies, thus highlighting the need for environmentally sound control strategies. Volatile organic compounds (VOCs) offer an environmentally benign alternative to synthetic chemical sprays and this study explored the use of VOCs as insect repellents and plant defence elicitors to control whiteflies on tomato in a commercial glasshouse setting. Limonene in the form of a volatile dispenser system was found to successfully repel whitefly from the target crop and increased fruit yield by 32% during a heavy whitefly infestation. Analysis of tomato herbivore induced plant volatiles (HIPVs) led us to select methyl salicylate (MeSA) as the plant elicitor and application of MeSA to un-infested tomato plants was found to successfully reduce whitefly population development and increase yield by 11%, although this difference was marginally statistically significant. Combination of these two methods was also effective but whitefly abundance in combined plots was similar to the standalone limonene treatment across the course of the experiment. All of the VOC based control methods we used had a negative impact on whitefly performance, with more pronounced effects during the first few weeks of infestation. In subsequent laboratory experiments, we found elevated peroxidase (POD) activity and a significant increase in TPX1 and PR1 transcripts in MeSA treated plants. This led us to deduce that MeSA immediately induced plant defences, rather than priming them. We did however see evidence for residual priming, as plants treated with MeSA and infested with whiteflies produced significantly higher levels of POD activity than whitefly infestation alone. Despite the fact that our treatments failed to synergise, our methods can be optimised further, and the effectiveness of the standalone treatments is promising for future studies. In particular, our repellent limonene dispensers were extremely effective at deterring whiteflies and offer a low economic cost and easy to implement whitefly control option. The methods we have used here could be incorporated into current integrated pest management (IPM) systems, a sustainable approach to pest control which will be central to our efforts to manage whitefly populations under glass in the future.
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http://dx.doi.org/10.1007/s10886-020-01229-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677274PMC
December 2020

Cretaceous dinosaur bone contains recent organic material and provides an environment conducive to microbial communities.

Elife 2019 06 18;8. Epub 2019 Jun 18.

Department of Geosciences, Princeton University, Princeton, United States.

Fossils were thought to lack original organic molecules, but chemical analyses show that some can survive. Dinosaur bone has been proposed to preserve collagen, osteocytes, and blood vessels. However, proteins and labile lipids are diagenetically unstable, and bone is a porous open system, allowing microbial/molecular flux. These 'soft tissues' have been reinterpreted as biofilms. Organic preservation versus contamination of dinosaur bone was examined by freshly excavating, with aseptic protocols, fossils and sedimentary matrix, and chemically/biologically analyzing them. Fossil 'soft tissues' differed from collagen chemically and structurally; while degradation would be expected, the patterns observed did not support this. 16S rRNA amplicon sequencing revealed that dinosaur bone hosted an abundant microbial community different from lesser abundant communities of surrounding sediment. Subsurface dinosaur bone is a relatively fertile habitat, attracting microbes that likely utilize inorganic nutrients and complicate identification of original organic material. There exists potential post-burial taphonomic roles for subsurface microorganisms.
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http://dx.doi.org/10.7554/eLife.46205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581507PMC
June 2019

Companion planting with French marigolds protects tomato plants from glasshouse whiteflies through the emission of airborne limonene.

PLoS One 2019 1;14(3):e0213071. Epub 2019 Mar 1.

School of Natural and Environmental Sciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom.

Horticulturalists and gardeners in temperate regions often claim that planting marigolds next to tomato plants protects the tomatoes from the glasshouse whitefly (Trialeurodes vaporariorum Westwood). If shown to hold true, this technique could be used in larger-scale tomato production, protecting the crop and helping to introduce greater plant diversity into these agro-ecosystems. Here we present two large-scale glasshouse trials corresponding to the two main ways growers are likely to use marigolds to control whiteflies. In the first, marigolds are grown next to tomato throughout the growing period and we quantify whitefly population growth from the seedling stage over a 48 day infestation period. Here we show that association with marigolds significantly slows whitefly population development. Introducing additional whitefly-attractive 'pull' plants around the perimeter of plots has little effect, but reducing the proportion of marigolds and introducing other non-hosts of whiteflies (basil, nasturtium and Chinese cabbage) also reduces whitefly populations on tomato. The second experiment assesses the efficacy of marigolds when used as an 'emergency' measure. Here we allow whitefly populations to build to a high density on unprotected tomatoes then introduce marigolds and assess whitefly population over a further period. Following laboratory work showing limonene to be a major chemical component of French marigolds and a negative behaviour response of whiteflies to this compound, limonene dispensers are added as an additional treatment to this experiment. "Emergency" marigold companion planting yielded minimal reductions in whitefly performance, but the use of limonene dispensers was more effective. Our work indicates that companion planting short vine tomatoes with French marigolds throughout the growing season will slow development of whitefly populations. Introducing marigolds to unprotected tomatoes after significant whitefly build-up will be less effective. The use of limonene dispensers placed near to tomato plants also shows promise. It is argued that this work supports the possibility of the development of a mixture of tomato companion plants that infer 'associational resistance' against many major invertebrate pests of tomato. Such a mixture, if comprising edible or ornamental plants, would be economically viable, would reduce the need for additional chemical and biological control, and, if used outdoors, would generate plant-diverse agro-ecosystems that are better able to harbour invertebrate wildlife.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213071PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396911PMC
November 2019

Publishing peer review materials.

F1000Res 2018 17;7:1655. Epub 2018 Oct 17.

PeerJ, London, UK.

Publishing peer review materials alongside research articles promises to make the peer review process more transparent as well as making it easier to recognise these contributions and give credit to peer reviewers. Traditionally, the peer review reports, editors letters and author responses are only shared between the small number of people in those roles prior to publication, but there is a growing interest in making some or all of these materials available. A small number of journals have been publishing peer review materials for some time, others have begun this practice more recently, and significantly more are now considering how they might begin. This article outlines the outcomes from a recent workshop among journals with experience in publishing peer review materials, in which the specific operation of these workflows, and the challenges, were discussed. Here, we provide a draft as to how to represent these materials in the JATS and Crossref data models to facilitate the coordination and discoverability of peer review materials, and seek feedback on these initial recommendations.
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http://dx.doi.org/10.12688/f1000research.16460.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206614PMC
September 2019

Unusual presentation of aortic dissection with bilateral testicular pain and rapidly deteriorating renal function.

Urology 2014 May 16;83(5):989-91. Epub 2013 Oct 16.

Department of Renal Medicine, King's College Hospital, London, United Kingdom.

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http://dx.doi.org/10.1016/j.urology.2013.08.027DOI Listing
May 2014

Ancient lipids reveal continuity in culinary practices across the transition to agriculture in Northern Europe.

Proc Natl Acad Sci U S A 2011 Nov 24;108(44):17910-5. Epub 2011 Oct 24.

BioArCh, Department of Archaeology, University of York, York YO10 5YW, United Kingdom.

Farming transformed societies globally. Yet, despite more than a century of research, there is little consensus on the speed or completeness of this fundamental change and, consequently, on its principal drivers. For Northern Europe, the debate has often centered on the rich archaeological record of the Western Baltic, but even here it is unclear how quickly or completely people abandoned wild terrestrial and marine resources after the introduction of domesticated plants and animals at ∼4000 calibrated years B.C. Ceramic containers are found ubiquitously on these sites and contain remarkably well-preserved lipids derived from the original use of the vessel. Reconstructing culinary practices from this ceramic record can contribute to longstanding debates concerning the origins of farming. Here we present data on the molecular and isotopic characteristics of lipids extracted from 133 ceramic vessels and 100 carbonized surface residues dating to immediately before and after the first evidence of domesticated animals and plants in the Western Baltic. The presence of specific lipid biomarkers, notably ω-(o-alkylphenyl)alkanoic acids, and the isotopic composition of individual n-alkanoic acids clearly show that a significant proportion (∼20%) of ceramic vessels with lipids preserved continued to be used for processing marine and freshwater resources across the transition to agriculture in this region. Although changes in pottery use are immediately evident, our data challenge the popular notions that economies were completely transformed with the arrival of farming and that Neolithic pottery was exclusively associated with produce from domesticated animals and plants.
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http://dx.doi.org/10.1073/pnas.1107202108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207664PMC
November 2011

Symptoms in the month before death for stage 5 chronic kidney disease patients managed without dialysis.

J Pain Symptom Manage 2010 Sep 26;40(3):342-52. Epub 2010 Jun 26.

Department of Palliative Care, Policy and Rehabilitation, King's College London, London, United Kingdom.

Context: There is little evidence on the symptoms experienced by those with advanced (Stage 5) chronic kidney disease (CKD), managed without dialysis, as they approach death. As palliative care extends to noncancer illnesses, understanding symptom prevalence and severity close to death will clarify which symptom interventions are most needed and which elements of (largely cancer-driven) models of palliative care best translate into end-of-life care for this population.

Objectives: To determine symptom prevalence and severity in the last month of life for patients with Stage 5 CKD, managed without dialysis.

Methods: Longitudinal symptom survey in three U.K. renal units, using the patient-completed Memorial Symptom Assessment Scale-Short Form (MSAS-SF). We calculated the prevalence of individual symptoms (with 95% confidence intervals [CI] to reflect sample size), plus MSAS-SF subscales, in the month before death. Comparison is made with previously published data on symptoms in the last month of life in advanced cancer, also measured using the MSAS-SF.

Results: Seventy-four patients (mean age: 81 years; standard deviation [SD]: 6.8) were recruited (response rate: 73%); 49 (66%) died during follow-up (mean age: 81 years; SD: 5.7). "Month before death" symptom data were available for 43 (88%) of the 49 participants who died. Median time of data collection was 18 days from death (interquartile range: 12-26 days). More than half had lack of energy (86%; 95% CI: 73%-94%), itch (84%; 70%-93%), drowsiness (82%; 68%-91%), dyspnea (80%; 66%-90%), poor concentration (76%; 61%-87%), pain (73%; 59%-85%), poor appetite (71%; 57%-83%), swelling arms/legs (71%; 57%-83%), dry mouth (69%; 55%-82%), constipation (65%; 50%-78%), and nausea (59%; 44%-73%). Levels of distress correspond to prevalence, with the exception of dyspnea, which was disproportionately more distressing. The median number of symptoms reported was 16.6 (range: 6-27), rising to 20.4 (range: 7-34) if additional renal symptoms were included. On average, psychological distress was moderate (mean MSAS-PSYCH: 1.55) but with wide variation (SD: 0.50; range: 0.17-2.40), suggesting diverse levels of individual distress. The prevalence of both physical and psychological symptoms and the number reported were higher than those in advanced cancer patients in the month before death.

Conclusion: Stage 5 CKD patients have clinically important physical and psychological symptom burdens in the last month of life, similar or greater than those in advanced cancer patients. Symptoms must be addressed through routine symptom assessment, appropriate interventions, and with pertinent models of end-of-life care.
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http://dx.doi.org/10.1016/j.jpainsymman.2010.01.021DOI Listing
September 2010

Predictors of renal outcome in HIV-associated nephropathy.

Clin Infect Dis 2008 Apr;46(8):1282-9

Academic Dept. of HIV/GUM, King's College London School of Medicine at Guy's, King's College, London, United Kingdom.

Background: Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is an important cause of end-stage renal disease among African American patients. This study was performed to study the epidemiology of HIVAN in a predominantly black African population and the impact of highly active antiretroviral therapy and other factors on the development of end-stage renal disease.

Methods: We retrospectively identified all patients with HIVAN, defined by biopsy or strict clinical criteria, in 8 clinics in the United Kingdom. Baseline renal function, HIV parameters, renal pathological index of chronic damage, and responses to highly active antiretroviral therapy were analyzed, and factors associated with adverse renal outcome were identified.

Results: From 1998 through 2004, we studied 16,834 patients, 61 of whom had HIVAN. HIVAN prevalence in black patients was 0.93%, and HIVAN incidence in those without renal disease at baseline was 0.61 per 1000 person-years. After a median of 4.2 years, 34 patients (56%) had developed end-stage renal disease. There were no significant differences in renal function and HIV parameters at baseline, time to initiation of highly active antiretroviral therapy, and rates of HIV RNA suppression between the 20 patients who developed end-stage renal disease >3 months after receiving the HIVAN diagnosis and the 23 patients who maintained stable renal function. However, the index of chronic damage score was significantly higher in those who developed end-stage renal disease (P < .001), and an index of chronic damage score >75 was associated with shorter renal survival (P < .001).

Conclusions: Whereas overall patient survival suggested an important benefit of highly active antiretroviral therapy, no additional renal benefit of early initiation of highly active antiretroviral therapy or viral suppression could be demonstrated in this large cohort of patients with established HIVAN. Severity of chronic kidney damage, as quantified by biopsy, was the strongest predictor of renal outcome.
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http://dx.doi.org/10.1086/529385DOI Listing
April 2008

Symptoms in advanced renal disease: a cross-sectional survey of symptom prevalence in stage 5 chronic kidney disease managed without dialysis.

J Palliat Med 2007 Dec;10(6):1266-76

Department of Palliative Care, Policy and Rehabilitation, Weston Education Centre, King's College London, London, United Kingdom.

Background: Numbers of patients with stage 5 chronic kidney disease (CKD) managed conservatively (without dialysis) are increasing steadily but prevalence and severity of symptoms in this population are not yet known.

Aim: To describe symptom prevalence, symptom severity, and total symptom burden in patients with stage 5 CKD managed conservatively.

Method: A cross-sectional survey of patients with stage 5 CKD managed conservatively, in three U.K. renal units. Symptoms were assessed using the patient-completed Memorial Symptom Assessment Scale Short Form (MSAS-SF), with additional renal symptoms.

Results: Sixty-six patients were recruited (response rate, 62%), with mean age 82 years (standard deviation [SD] +/- 6.6), and mean estimated glomerular filtration rate 11.2 mL/min (SD +/- 2.8). Symptoms reported by more than one third or 33% of patients were (95% confidence intervals shown in parentheses): lack of energy, 76% (66%-84%); pruritus, 74% (65%-82%); drowsiness, 65% (54%-74%); dyspnea, 61% (50%-70%); edema, 58% (47%-66%); pain, 53% (42%-63%); dry mouth, 50% (39%-60%); muscle cramps, 50% (39%-60%); restless legs, 48% (38%-58%); lack of appetite, 47% (37%-58%); poor concentration, 44% (34%-54%); dry skin, 42% (32%-53%); sleep disturbance, 41% (32%-51%); and constipation, 35% (26%-45%). Mean number of symptoms reported on MSAS-SF was 11.58 (SD +/- 5.2), with an additional 2.77 (SD +/- 1.7) renal symptoms. Symptoms were also most severe in the more prevalent symptoms. Pain was an exception, with disproportionately greater severity (32% of all patients reported moderate/severe pain).

Conclusion: This study demonstrates that patients with stage 5 CKD have considerable symptom control needs, similar to advanced cancer populations, but with different patterns of individual symptoms and severity, particularly pain. Implications for palliative care, hospice, and nephrology services in planning and providing care are discussed.
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http://dx.doi.org/10.1089/jpm.2007.0017DOI Listing
December 2007

The use of opioid analgesia in end-stage renal disease patients managed without dialysis: recommendations for practice.

J Pain Palliat Care Pharmacother 2007 ;21(2):5-16

Department of Palliative Care & Policy, Kings College, London.

The numbers of patients dying with end-stage renal disease (ESRD), particularly those managed conservatively (without dialysis) or withdrawing from dialysis is increasing rapidly in developed countries. There is growing awareness of the extensive symptom control needs of these patients. Pain is a common problem, and has been both under-recognized and under-treated. It is challenging to manage, largely because of the constraints very poor renal function places on use of medication. Although pharmacological reviews of opioid use in renal failure have been published, there is a need for clinical recommendations to aid palliative and renal specialists in providing effective pain control. This review describes the pharmacological evidence for and against the use of the different opioid medications, and translates this into clinical recommendations for ESRD patients managed conservatively, not for those on dialysis for whom there are different pharmacological considerations. Acetaminophen (paracetamol) is recommended at Step 1 of the World Health Organization ladder. Of the Step 2 analgesics, tramadol is the least problematic, although dose reduction and increased dosing interval are required, and caution should be exercised. Of the Step 3 analgesics, fentanyl, alfentanil and methadone are recommended. There is limited evidence for buprenorphine, although theoretical reasons why it may be a good choice for these patients. Hydromorphone and oxycodone cannot be recommended because of extremely limited evidence, although each is likely a better choice than morphine or diamorphine. Morphine and diamorphine themselves are not recommended because of known accumulation of potentially toxic metabolites.
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October 2007

Dialysis or not? A comparative survival study of patients over 75 years with chronic kidney disease stage 5.

Nephrol Dial Transplant 2007 Jul 4;22(7):1955-62. Epub 2007 Apr 4.

Department of Palliative Care and Policy, King's College Hospital, London, Se5 9RJ, UK.

Background: The number of elderly patients with chronic kidney disease (CKD) stage 5 is steadily increasing. Evidence is needed to inform decision-making for or against dialysis, especially in those patients with multiple comorbid conditions for whom dialysis may not increase survival. We therefore compared survival of elderly patients with CKD stage 5, managed either with dialysis or conservatively (without dialysis), after the management decision had been made, and explored which of several key variables were independently associated with survival.

Methods: A retrospective analysis of the survival of all over 75 years with CKD stage 5 attending dedicated multidisciplinary pre-dialysis care clinics (n=129) was performed. Demographic and comorbidity data were collected on all patients. Survival was defined as the time from estimated GFR<15 ml/min to either death or study endpoint.

Results: One- and two-year survival rates were 84% and 76% in the dialysis group (n=52) and 68% and 47% in the conservative group (n=77), respectively, with significantly different cumulative survival (log rank 13.6, P<0.001). However, this survival advantage was lost in those patients with high comorbidity scores, especially when the comorbidity included ischaemic heart disease.

Conclusions: In CKD stage 5 patients over 75 years, who receive specialist nephrological care early, and who follow a planned management pathway, the survival advantage of dialysis is substantially reduced by comorbidity and ischaemic heart disease in particular. Comorbidity should be a major consideration when advising elderly patients for or against dialysis.
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http://dx.doi.org/10.1093/ndt/gfm153DOI Listing
July 2007

Mild hypothermia, but not propofol, is neuroprotective in organotypic hippocampal cultures.

Anesth Analg 2005 Jan;100(1):215-25

Department of Anesthesia and Perioperative Care, University of California at San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0542, USA.

The neuroprotective potency of anesthetics such as propofol compared to mild hypothermia remains undefined. Therefore, we determined whether propofol at two clinically relevant concentrations is as effective as mild hypothermia in preventing delayed neuron death in hippocampal slice cultures (HSC). Survival of neurons was assessed 2 and 3 days after 1 h oxygen and glucose deprivation (OGD) either at 37 degrees C (with or without 10 or 100 microM propofol) or at an average temperature of 35 degrees C during OGD (mild hypothermia). Cell death in CA1, CA3, and dentate neurons in each slice was measured with propidium iodide fluorescence. Mild hypothermia eliminated death in CA1, CA3, and dentate neurons but propofol protected dentate neurons only at a concentration of 10 microM; the more ischemia vulnerable CA1 and CA3 neurons were not protected by either 10 microM or 100 microM propofol. In slice cultures, the toxicity of 100 muM N-methyl-D-aspartate (NMDA), 500 microM glutamate, and 20 microM alpha-amino-5-methyl-4-isoxazole propionic acid (AMPA) was not reduced by 100 microM propofol. Because propofol neuroprotection may involve gamma-aminobutyric acid (GABA)-mediated indirect inhibition of glutamate receptors (GluRs), the effects of propofol on GluR activity (calcium influx induced by GluR agonists) were studied in CA1 neurons in HSC, in isolated CA1 neurons, and in cortical brain slices. Propofol (100 and 200 microM, approximate burst suppression concentrations) decreased glutamate-mediated [Ca2+]i increases (Delta[Ca2+]i) responses by 25%-35% in isolated CA1 neurons and reduced glutamate and NMDA Delta[Ca2+]i in acute and cultured hippocampal slices by 35%-50%. In both CA1 neurons and cortical slices, blocking GABAA receptors with picrotoxin reduced the inhibition of GluRs substantially. We conclude that mild hypothermia, but not propofol, protects CA1 and CA3 neurons in hippocampal slice cultures subjected to oxygen and glucose deprivation. Propofol was not neuroprotective at concentrations that reduce glutamate and NMDA receptor responses in cortical and hippocampal neurons.
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http://dx.doi.org/10.1213/01.ANE.0000142129.17005.73DOI Listing
January 2005

Adaptive responses of vertebrate neurons to hypoxia.

J Exp Biol 2002 Dec;205(Pt 23):3579-86

Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143-0542 USA.

The damage caused to mammalian neurons during ischaemic events in the brain (e.g. following a stroke), is an area of major interest to neuroscientists. The neurons of hypoxia-tolerant vertebrates offer unique models for identifying new strategies to enhance the survival of hypoxia-vulnerable neurons. In this review, we describe recent advances in our understanding of how hypoxia-tolerant neurons detect decreases in oxygen and create signals that have immediate and long-term effects on cell function and survival. Sensing and adapting to low oxygen tension involves numerous modalities with different times of activation and effect. Sensors include membrane proteins such as ionotropic ion channels, membrane or cytosolic heme proteins, mitochondrial proteins and/or oxygen sensitive transcription factors such as HIF-1alpha and NFkappaB. Signaling molecules involved in O(2) sensing include mitogen-activated protein kinases, ions such as Ca(2+) and metabolites such as adenosine. These signals act rapidly to reduce the conductance of ion channels (ion flux arrest) and production of energy (metabolic arrest), and slowly to activate specific genes. The ability to construct an energy budget, illustrating which physiological processes are depressed during both long-term and acute metabolic suppression in hypoxia-tolerant neurons, would be of significant value in devising new strategies for neuroprotection. Additionally it is not known how metabolism is regulated at 'pilot-light' levels at which energy-producing and energy-consuming processes are balanced. The regulation of organelle and cell fate during long-term hypoxia is almost completely unexplored, and whether programmed cell death and regeneration of lost neurons occur following protracted dormancy is also of considerable interest.
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December 2002

Molecular adaptations for survival during anoxia: lessons from lower vertebrates.

Neuroscientist 2002 Jun;8(3):234-42

Department of Anesthesia, University of California, San Francisco, USA.

Anoxia-tolerant neurons from several species of animals may offer unparalleled opportunities to identify strategies that might be employed to enhance the hypoxia or ischemia tolerance of vulnerable neurons. In this review, the authors describe how the response of hypoxia-tolerant neurons to limited oxygen supply involves a suite of mechanisms that reduce energy expenditure in concert with decreased energy availability. This response avoids energy depletion, excitotoxic neuronal death, and apoptosis. Suppression of ion channel functions, particularly those of the ionotropic glutamate receptors, is a response common in hypoxia-tolerant neurons. The depression of excitability thereby achieved is essential given that the fundamental response to oxygen lack in anoxia-tolerant cells is a throttling down of metabolism to "pilot-light" levels. Many different types of processes have been found to down-regulate ion channel function. These include phosphorylation control, interactions with intracellular and extracellular ions, removal of active receptors from the neurolemma, and the direct sensing of oxygen by Na+ and K+ channels. Changes in [Ca2+]i may initiate a protective down-regulation of many different pumps or channels. Transcriptional events leading to differential and/or decreased expression of receptors, proteins, and their subunits are probably very important but little studied.
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http://dx.doi.org/10.1177/1073858402008003009DOI Listing
June 2002

Comparison of the effects of cyclosporin a on the metabolism of perfused rat brain slices during normoxia and hypoxia.

J Cereb Blood Flow Metab 2002 Mar;22(3):342-52

Department of Biology and Chemistry, University of Bremen, Bremen, Germany.

The authors evaluated and compared the metabolic effects of cyclosporin A in the rat brain during normoxia and hypoxia/reperfusion. Ex vivo 31P magnetic resonance spectroscopy experiments based on perfused rat brain slices showed that under normoxic conditions, 500 microg/L cyclosporin A significantly reduced mitochondrial energy metabolism (nucleotide triphosphate, 83 +/- 9% of controls; phosphocreatine, 69 +/- 9%) by inhibition of the Krebs cycle (glutamate, 77 +/- 5%) and oxidative phosphorylation (NAD+, 65 +/- 14%) associated with an increased generation of reactive oxygen species (285 +/- 78% of control). However, the same cyclosporin A concentration (500 microg/L) was found to be the most efficient concentration to inhibit the hypoxia-induced mitochondrial release of Ca2+ in primary rat hippocampal cells with cytosolic Ca2+ concentrations not significantly different from normoxic controls. Addition of 500 microg/L cyclosporin A to the perfusion medium protected high-energy phosphate metabolism (nucleotide triphosphate, 11 +/- 15% of control vs. 35 +/- 9% with 500 microg/L cyclosporin A) and the intracellular pH (6.2 +/- 0.1 control vs. 6.6 +/- 0.1 with cyclosporin A) in rat brain slices during 30 minutes of hypoxia. Results indicate that cyclosporin A simultaneously decreases and protects cell glucose and energy metabolism. Whether the overall effect was a reduction or protection of cell energy metabolism depended on the concentrations of both oxygen and cyclosporin A in the buffer solution.
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http://dx.doi.org/10.1097/00004647-200203000-00012DOI Listing
March 2002