Pub Date : 2014-01-01DOI: 10.1093/BIOHORIZONS/HZU013
R. Mulvey
Alzheimer’s disease is a growing concern with no satisfactory current treatment solution. Contemporary stem cell research offers a new arena for development in this field. Transplantation of stem cells into the damaged brain brings hope of repair to damaged neurons. This appears to operate via a ‘bystander effect’ whereby neurotrophins secreted by the cells act as a neuro protectant, rather than a cell replacement mechanism as some have postulated. Such treatments can slow or even reverse cognitive decline. Research into neural stem cell transplantation has shown reversal of cognitive decline in animal models of disease via the mechanism of brain-derived neurotrophic factor secretion. Studies using nerve growth factor secreting stem cells have showed promising results with cognitive decline reversed in animal models of the disease. A Phase 1 clinical trial also showed promising reversal of cognitive decline in human subjects using transplantation of nerve growth factor secreting fibroblasts. Mesenchymal stem cells have also shown promise, and results from human trials are awaited. Induced pluripotent stem cells have provided a successful model of human disease in vitro. Although early results from transplant studies are encouraging, a lot more research will be needed before these preliminary advances can be translated to therapies with a strong evidence base to be used in practice.
{"title":"Stem cells slow cognitive decline in Alzheimer's disease via neurotrophin action","authors":"R. Mulvey","doi":"10.1093/BIOHORIZONS/HZU013","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZU013","url":null,"abstract":"Alzheimer’s disease is a growing concern with no satisfactory current treatment solution. Contemporary stem cell research offers a new arena for development in this field. Transplantation of stem cells into the damaged brain brings hope of repair to damaged neurons. This appears to operate via a ‘bystander effect’ whereby neurotrophins secreted by the cells act as a neuro protectant, rather than a cell replacement mechanism as some have postulated. Such treatments can slow or even reverse cognitive decline. Research into neural stem cell transplantation has shown reversal of cognitive decline in animal models of disease via the mechanism of brain-derived neurotrophic factor secretion. Studies using nerve growth factor secreting stem cells have showed promising results with cognitive decline reversed in animal models of the disease. A Phase 1 clinical trial also showed promising reversal of cognitive decline in human subjects using transplantation of nerve growth factor secreting fibroblasts. Mesenchymal stem cells have also shown promise, and results from human trials are awaited. Induced pluripotent stem cells have provided a successful model of human disease in vitro. Although early results from transplant studies are encouraging, a lot more research will be needed before these preliminary advances can be translated to therapies with a strong evidence base to be used in practice.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZU013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-01-01DOI: 10.1093/BIOHORIZONS/HZU014
S. Harbison
Multiple sclerosis is a chronic demyelinating autoimmune disease with uncertain aetiology. Due to the heterogeneity of the disease, patients may present with a wide variety of neurological symptoms such as optic neuritis, sensory deficits or cerebel lar dysfunction. It remains a disease showing little hope in terms of finding a cure. Although current therapies, such as interferon-β and glatiramer acetate, provide symptomatic relief and can delay the degenerative process, there is still a large impact on quality of life as these therapies lack an ability to reverse damage occurring prior to treatment. Recently, cell therapy has emerged as a promising treatment with signs of recovery both pathologically and clinically in a variety of animal models. Given the multifaceted capabilities of the various stem cells, including immunomodulation and neuroprotection, their potential use as a comprehensive therapy is much more promising than any pharmacological therapy to date. Here, the latest advances of cell therapy are discussed, in terms of potential efficacy, the various cell types that are used, their mecha nisms of action and the obstacles that still need to be overcome for translation into a clinical setting.
{"title":"Cell therapy for multiple sclerosis: a new hope","authors":"S. Harbison","doi":"10.1093/BIOHORIZONS/HZU014","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZU014","url":null,"abstract":"Multiple sclerosis is a chronic demyelinating autoimmune disease with uncertain aetiology. Due to the heterogeneity of the disease, patients may present with a wide variety of neurological symptoms such as optic neuritis, sensory deficits or cerebel lar dysfunction. It remains a disease showing little hope in terms of finding a cure. Although current therapies, such as interferon-β and glatiramer acetate, provide symptomatic relief and can delay the degenerative process, there is still a large impact on quality of life as these therapies lack an ability to reverse damage occurring prior to treatment. Recently, cell therapy has emerged as a promising treatment with signs of recovery both pathologically and clinically in a variety of animal models. Given the multifaceted capabilities of the various stem cells, including immunomodulation and neuroprotection, their potential use as a comprehensive therapy is much more promising than any pharmacological therapy to date. Here, the latest advances of cell therapy are discussed, in terms of potential efficacy, the various cell types that are used, their mecha nisms of action and the obstacles that still need to be overcome for translation into a clinical setting.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZU014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-01-01DOI: 10.1093/BIOHORIZONS/HZT012
L. Rogers, A. Lake, K. White, M. Hardy, E. White
Superoxide anions have been associated with many aspects of cardiovascular disease. Menadione is a superoxide anion donor that alters the heart’s electrical and mechanical functions. The aim of this study was to demonstrate simultaneous changes in intracellular Ca 2+ ([Ca 2+ ]i) and mechanical activity in intact adult cardiac myocytes, and mechanical activity and electrical activity in isolated whole hearts in order to provide greater insight into the mechanisms associated with the detrimental effects of menadione on the myocardium. Isolated hearts from adult male Wistar rats (n = 11, 200–250 g) were Langendorff perfused at 38°C with a Krebs–Henseleit solution. A saline-filled balloon was placed in the left ventricle (LV) in order to measure diastolic and developed pressure. Monophasic action potentials were simultaneously recorded from the epicardial surface. External stimulation at 5 Hz and intrinsic pacing were used throughout a 10 min control period and 30 min exposure to 50 µM menadione. Single LV myocytes (n = 7 from n = 4 animals) were loaded with the Ca2+-indicator Fura4-AM, stimulated at 1 Hz and exposed to 50 µM menadione. Myocyte length was simultaneously measured with [Ca 2+ ]i using a video edge detection system. In isolated hearts, exposure to menadione significantly decreased contractility and action potential duration (with a simi lar time course); intrinsic heart rate and rhythmicity. Diastolic pressure was significantly increased. In single adult myocytes, menadione caused a significant increase in diastolic [Ca 2+ ]i and a decrease in resting cell length and led to spontaneous release of [Ca 2+ ]i. We conclude that the effects of menadione upon electrical and mechanical activity of the heart are at least in part a consequence of dysregulation of [Ca 2+ ]i handling and the subsequent increase in diastolic [Ca 2+ ] alterations in [Ca 2+ ]i are consistent with the generation of delayed after depolarization arrhythmias.
{"title":"Effects of superoxide donor menadione in adult Rat myocardium are associated with increased diastolic intracellular calcium","authors":"L. Rogers, A. Lake, K. White, M. Hardy, E. White","doi":"10.1093/BIOHORIZONS/HZT012","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZT012","url":null,"abstract":"Superoxide anions have been associated with many aspects of cardiovascular disease. Menadione is a superoxide anion donor that alters the heart’s electrical and mechanical functions. The aim of this study was to demonstrate simultaneous changes in intracellular Ca 2+ ([Ca 2+ ]i) and mechanical activity in intact adult cardiac myocytes, and mechanical activity and electrical activity in isolated whole hearts in order to provide greater insight into the mechanisms associated with the detrimental effects of menadione on the myocardium. Isolated hearts from adult male Wistar rats (n = 11, 200–250 g) were Langendorff perfused at 38°C with a Krebs–Henseleit solution. A saline-filled balloon was placed in the left ventricle (LV) in order to measure diastolic and developed pressure. Monophasic action potentials were simultaneously recorded from the epicardial surface. External stimulation at 5 Hz and intrinsic pacing were used throughout a 10 min control period and 30 min exposure to 50 µM menadione. Single LV myocytes (n = 7 from n = 4 animals) were loaded with the Ca2+-indicator Fura4-AM, stimulated at 1 Hz and exposed to 50 µM menadione. Myocyte length was simultaneously measured with [Ca 2+ ]i using a video edge detection system. In isolated hearts, exposure to menadione significantly decreased contractility and action potential duration (with a simi lar time course); intrinsic heart rate and rhythmicity. Diastolic pressure was significantly increased. In single adult myocytes, menadione caused a significant increase in diastolic [Ca 2+ ]i and a decrease in resting cell length and led to spontaneous release of [Ca 2+ ]i. We conclude that the effects of menadione upon electrical and mechanical activity of the heart are at least in part a consequence of dysregulation of [Ca 2+ ]i handling and the subsequent increase in diastolic [Ca 2+ ] alterations in [Ca 2+ ]i are consistent with the generation of delayed after depolarization arrhythmias.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZT012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-01-01DOI: 10.1093/BIOHORIZONS/HZU009
C. Stephenson, C. Black
This review charts the evolution of phytoremediation from its earliest beginnings, with the discovery of metal tolerant plants in the 16th century and metabolism of organic pollutants by plants in the 1940s. The rapid expansion of research in the early 1990s led to many crucial discoveries but failed to surmount the fundamental limitations that often impede commercial application of phytoremediation. It is argued that phytoremediation was saved from being forgotten by its evolution under the new term phytotechnology, or ‘the application of science and engineering to examine problems and provide solutions using plants’. This review explores the use of phytotechnology for ecological engineering using constructed wetlands and evapotranspiration caps as landfill covers. Finally, the transfer of phytotechnology to developing countries, where it has great potential to solve the growing problem of pollution, is examined. The development of phytotechnology can be perceived as an illustration of the modern evolution of scientific thought, from the traditional reductionist view to a wider holistic approach which takes into account the natural environment and our need to preserve it. It is hoped that the evolution of both will allow for increasing conservation of finite resources without sacrificing continued development.
{"title":"One step forward, two steps back: the evolution of phytoremediation into commercial technologies","authors":"C. Stephenson, C. Black","doi":"10.1093/BIOHORIZONS/HZU009","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZU009","url":null,"abstract":"This review charts the evolution of phytoremediation from its earliest beginnings, with the discovery of metal tolerant plants in the 16th century and metabolism of organic pollutants by plants in the 1940s. The rapid expansion of research in the early 1990s led to many crucial discoveries but failed to surmount the fundamental limitations that often impede commercial application of phytoremediation. It is argued that phytoremediation was saved from being forgotten by its evolution under the new term phytotechnology, or ‘the application of science and engineering to examine problems and provide solutions using plants’. This review explores the use of phytotechnology for ecological engineering using constructed wetlands and evapotranspiration caps as landfill covers. Finally, the transfer of phytotechnology to developing countries, where it has great potential to solve the growing problem of pollution, is examined. The development of phytotechnology can be perceived as an illustration of the modern evolution of scientific thought, from the traditional reductionist view to a wider holistic approach which takes into account the natural environment and our need to preserve it. It is hoped that the evolution of both will allow for increasing conservation of finite resources without sacrificing continued development.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZU009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-01-01DOI: 10.1093/BIOHORIZONS/HZU007
A. Morgan
along with the fractional inhibitory concentration index (FICI) to test for synergy. A value of ≤0.5 defined synergy; 0.5 < FICI < 4 defined no interaction; ≥4 defined antagonism. No results of synergy were found; there were five results of no interaction and six results of antagonism. The MIC of ceftazidime was 3 µg/ml and the MBC was 4 µg/ml. The MIC of gentamicin was 0.25 µg/ ml and the MBC was 3 µg/ml. The combination of gentamicin and ceftazidime is optimal at a volume ratio of 1:1, in this case 25 µl gentamicin/25 µl ceftazidime, where gentamicin has a concentration of 0.5 µg/ml and ceftazidime has a concentration of 0.25 µg/ml, when used against 50 µl of 1–2 × 10 6 colony forming units per millilitre of P. fluorescens in vitro. This study recommends that this combination therapy be studied in depth in vivo, and that clinicians understand that this combination of antibiotics does not have a synergistic effect when treating patients in this manner.
{"title":"The synergistic effect of gentamicin and ceftazidime against Pseudomonas fluorescens","authors":"A. Morgan","doi":"10.1093/BIOHORIZONS/HZU007","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZU007","url":null,"abstract":"along with the fractional inhibitory concentration index (FICI) to test for synergy. A value of ≤0.5 defined synergy; 0.5 < FICI < 4 defined no interaction; ≥4 defined antagonism. No results of synergy were found; there were five results of no interaction and six results of antagonism. The MIC of ceftazidime was 3 µg/ml and the MBC was 4 µg/ml. The MIC of gentamicin was 0.25 µg/ ml and the MBC was 3 µg/ml. The combination of gentamicin and ceftazidime is optimal at a volume ratio of 1:1, in this case 25 µl gentamicin/25 µl ceftazidime, where gentamicin has a concentration of 0.5 µg/ml and ceftazidime has a concentration of 0.25 µg/ml, when used against 50 µl of 1–2 × 10 6 colony forming units per millilitre of P. fluorescens in vitro. This study recommends that this combination therapy be studied in depth in vivo, and that clinicians understand that this combination of antibiotics does not have a synergistic effect when treating patients in this manner.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZU007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-01-01DOI: 10.1093/BIOHORIZONS/HZU010
R. Shotton
The display of the disturbance hiss by the Madagascar Hissing Cockroach ( Gromphadorhina portentosa ) is considered to be an anti-predatory response despite there being little direct evidence linking the hiss with survival. Many studies have investi-gated the roles of the aggression and courtship hisses, displayed in this social species, but few have considered the role of the disturbance hiss. This study looked at the stimulus for the disturbance hiss response by placing unfamiliar individuals into different social contexts. A total of 10 male and 10 female G. portentosa were kept separately before being placed into four different social situations for 5 min at a time. The individuals were placed into an established colony of all females , an established colony of all males and an established colony of mixed sex G. portentosa . The subjects were also placed in the presence of a predator, an Emperor Scorpion ( Pandinus imperator Koch). All interactions and hisses were recorded both by video and on a sound-recording device. There was a highly significant difference in the setting in which the disturbance hiss was shown and a highly significant difference in the display rates of the disturbance hiss between the sexes in general, with most displays of the disturbance hiss being when introduced to a mixed sex colony. The findings suggest that the role of the disturbance hiss is not an anti-predatory response when presented with a predator of limited auditory senses. Further study into the behavioural ecology of this species is recommended to understand the range of anti-predatory responses used by this species when presented with different predators. It was also found that there is some social context for the display of the disturbance hiss which warrants further study.
马达加斯加嘶嘶蟑螂(Gromphadorhina portentosa)发出的干扰嘶嘶声被认为是一种反捕食反应，尽管几乎没有直接证据将嘶嘶声与生存联系起来。许多研究调查了这种群居物种中表现出来的攻击性和求偶嘶嘶声的作用，但很少有人考虑到干扰嘶嘶声的作用。这项研究通过将不熟悉的个体置于不同的社会环境中来观察干扰嘶嘶反应的刺激因素。总共有10只雄性和10只雌性G. portentosa被分开饲养，然后被放置在四种不同的社会环境中，每次5分钟。这些个体被放置在一个由所有雌性组成的既定群体、一个由所有雄性组成的既定群体和一个由混合性别组成的既定群体中。受试者也被放置在捕食者——帝王蝎子(Pandinus imperator Koch)面前。所有的互动和嘶嘶声都通过视频和录音设备记录下来。在干扰嘶嘶声显示的环境和干扰嘶嘶声的显示率在两性之间普遍存在着高度显著的差异，大多数干扰嘶嘶声的显示是在引入混合性别群体时出现的。研究结果表明，当面对听觉有限的捕食者时，干扰嘶嘶的作用并不是一种反捕食反应。建议对该物种的行为生态学进行进一步研究，以了解该物种在面对不同捕食者时所使用的反捕食反应的范围。研究还发现，干扰嘶嘶声的出现有一定的社会背景，值得进一步研究。
{"title":"Testing the disturbance hiss of the Madagascar hissing Cockroach (Gromphadorhina portentosa) as an anti-predatory response","authors":"R. Shotton","doi":"10.1093/BIOHORIZONS/HZU010","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZU010","url":null,"abstract":"The display of the disturbance hiss by the Madagascar Hissing Cockroach ( Gromphadorhina portentosa ) is considered to be an anti-predatory response despite there being little direct evidence linking the hiss with survival. Many studies have investi-gated the roles of the aggression and courtship hisses, displayed in this social species, but few have considered the role of the disturbance hiss. This study looked at the stimulus for the disturbance hiss response by placing unfamiliar individuals into different social contexts. A total of 10 male and 10 female G. portentosa were kept separately before being placed into four different social situations for 5 min at a time. The individuals were placed into an established colony of all females , an established colony of all males and an established colony of mixed sex G. portentosa . The subjects were also placed in the presence of a predator, an Emperor Scorpion ( Pandinus imperator Koch). All interactions and hisses were recorded both by video and on a sound-recording device. There was a highly significant difference in the setting in which the disturbance hiss was shown and a highly significant difference in the display rates of the disturbance hiss between the sexes in general, with most displays of the disturbance hiss being when introduced to a mixed sex colony. The findings suggest that the role of the disturbance hiss is not an anti-predatory response when presented with a predator of limited auditory senses. Further study into the behavioural ecology of this species is recommended to understand the range of anti-predatory responses used by this species when presented with different predators. It was also found that there is some social context for the display of the disturbance hiss which warrants further study.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZU010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-01-01DOI: 10.1093/BIOHORIZONS/HZT003
K. Lloyd
Living with epilepsy, for the majority of patients, is a continuous cycle of careful monitoring and attention to health. When coupled with pregnancy, safety becomes the primary focus. Epileptic women with reproductive intentions are confronted with a dilemma to either continue or discontinue current medication. Remaining on medication incurs the possibility of foetal abnormalities. However, discontinuation of medication could result in an uncontrolled condition that is potentially life threatening for both mother and child. Valproic acid (VPA) is a monocarboxylic acid with unclear mechanism of action and this is widely prescribed for epilepsy, bipolar disorder, migraine, Alzheimer’s disease and recently, cancer and HIV polytherapies. Originally, low incidences of toxicity were reported; however, emerging teratogenic properties warranted further investigation. This paper examines the major contraindications that VPA facilitates during pregnancy and proposes the degree of teratogenic influence each may inflict upon the developing foetus. The relevant aspects addressed are drug accumulation within the foetus, oxidative stress, folate antagonism and histone deacetylase (HDAC) inhibition. Review of the literature has shown vast numbers of investigations proving and disproving various proposed mechanisms of VPA-induced teratogenicity; these are still largely undefined. Based on the evidence presented, HDAC inhibition provided the strongest association with terato genicity, followed closely by the formation of reactive oxygen species. Both were particularly influential in the first trimester of pregnancy when DNA dysregulation has the largest impact on foetal organ development. In comparison, drug accumulation posed a lower risk as VPA is not the primary substrate for the majority of drug transporters across the placenta and lastly, folate inhibition was considered the lowest risk as new evidence has highlighted that the natural progression of gestation increases folate deficiency irrespective of VPA. All the suggested mechanisms (and possibly many more) may be contributing factors, together with inter-patient variability, environmental and lifestyle factors, each of which is also undefined, and lead to an increased risk of the teratogenic effects of VPA.
{"title":"A scientific review: mechanisms of valproate-mediated teratogenesis","authors":"K. Lloyd","doi":"10.1093/BIOHORIZONS/HZT003","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZT003","url":null,"abstract":"Living with epilepsy, for the majority of patients, is a continuous cycle of careful monitoring and attention to health. When coupled with pregnancy, safety becomes the primary focus. Epileptic women with reproductive intentions are confronted with a dilemma to either continue or discontinue current medication. Remaining on medication incurs the possibility of foetal abnormalities. However, discontinuation of medication could result in an uncontrolled condition that is potentially life threatening for both mother and child. Valproic acid (VPA) is a monocarboxylic acid with unclear mechanism of action and this is widely prescribed for epilepsy, bipolar disorder, migraine, Alzheimer’s disease and recently, cancer and HIV polytherapies. Originally, low incidences of toxicity were reported; however, emerging teratogenic properties warranted further investigation. This paper examines the major contraindications that VPA facilitates during pregnancy and proposes the degree of teratogenic influence each may inflict upon the developing foetus. The relevant aspects addressed are drug accumulation within the foetus, oxidative stress, folate antagonism and histone deacetylase (HDAC) inhibition. Review of the literature has shown vast numbers of investigations proving and disproving various proposed mechanisms of VPA-induced teratogenicity; these are still largely undefined. Based on the evidence presented, HDAC inhibition provided the strongest association with terato genicity, followed closely by the formation of reactive oxygen species. Both were particularly influential in the first trimester of pregnancy when DNA dysregulation has the largest impact on foetal organ development. In comparison, drug accumulation posed a lower risk as VPA is not the primary substrate for the majority of drug transporters across the placenta and lastly, folate inhibition was considered the lowest risk as new evidence has highlighted that the natural progression of gestation increases folate deficiency irrespective of VPA. All the suggested mechanisms (and possibly many more) may be contributing factors, together with inter-patient variability, environmental and lifestyle factors, each of which is also undefined, and lead to an increased risk of the teratogenic effects of VPA.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZT003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60764860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-01-01DOI: 10.1093/BIOHORIZONS/HZT006
C. Halford
Nuclear enriched abundant transcript 1 (NEAT1) is a long non-coding RNA with two isoforms. Both are expressed constitutively and have been shown to play a crucial structural role in the formation of paraspeckles. Paraspeckles are subnuclear bodies which retain certain mRNAs, preventing their translation in the cytoplasm, thereby silencing the corresponding genes. This study aimed to assess the effects of knocking down NEAT1 by RNA interference on the Burkitt’s lymphoma cell line, BJAB. The results have shown that a targeted siRNA depletion of NEAT1 resulted in an increased number of cells displaying aberrant morphology, including the appearance of ‘giant cells’, multinucleated cells and cells with cytoplasmic vacuoles. Furthermore, NEAT1 down-regulation was accompanied with an increased level of apoptosis and decreased cell viability, assessed by acridine orange morphology staining, vital dye exclusion and (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4sulfophenyl)-2H-tetrazolium) assay. Taken together, the study strongly suggests that modulation of NEAT1 expression has a significant effect on the BJAB cell line. Such remarkable effects of changes of NEAT1 expression on the control of cell morphol ogy reported here indicate the potential significance of this gene in the development and progression of cancer and highlight the importance of further investigation into the role of NEAT1 dysregulation in autoimmune disease and oncogenesis.
{"title":"Preliminary investigation of the effects of silencing the non-coding RNA, NEAT1, on the Burkitt's lymphoma cell line BJAB","authors":"C. Halford","doi":"10.1093/BIOHORIZONS/HZT006","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZT006","url":null,"abstract":"Nuclear enriched abundant transcript 1 (NEAT1) is a long non-coding RNA with two isoforms. Both are expressed constitutively and have been shown to play a crucial structural role in the formation of paraspeckles. Paraspeckles are subnuclear bodies which retain certain mRNAs, preventing their translation in the cytoplasm, thereby silencing the corresponding genes. This study aimed to assess the effects of knocking down NEAT1 by RNA interference on the Burkitt’s lymphoma cell line, BJAB. The results have shown that a targeted siRNA depletion of NEAT1 resulted in an increased number of cells displaying aberrant morphology, including the appearance of ‘giant cells’, multinucleated cells and cells with cytoplasmic vacuoles. Furthermore, NEAT1 down-regulation was accompanied with an increased level of apoptosis and decreased cell viability, assessed by acridine orange morphology staining, vital dye exclusion and (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4sulfophenyl)-2H-tetrazolium) assay. Taken together, the study strongly suggests that modulation of NEAT1 expression has a significant effect on the BJAB cell line. Such remarkable effects of changes of NEAT1 expression on the control of cell morphol ogy reported here indicate the potential significance of this gene in the development and progression of cancer and highlight the importance of further investigation into the role of NEAT1 dysregulation in autoimmune disease and oncogenesis.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZT006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60764958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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