AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function

Science.gov (United States)

Taniane, Caitlin; Farrell, Geoffrey; Arias, Irwin M.; Lippincott-Schwartz, Jennifer; Fu, Dong

2016-01-01

Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury. PMID:27792760

Mitochondrial targeted neuron focused genes in hippocampus of rats with traumatic brain injury.

Science.gov (United States)

Sharma, Pushpa; Su, Yan A; Barry, Erin S; Grunberg, Neil E; Lei, Zhang

2012-09-01

Mild traumatic brain injury (mTBI) represents a major health problem in civilian populations as well as among the military service members due to (1) lack of effective treatments, and (2) our incomplete understanding about the progression of secondary cell injury cascades resulting in neuronal cell death due to deficient cellular energy metabolism and damaged mitochondria. The aim of this study was to identify and delineate the mitochondrial targeted genes responsible for altered brain energy metabolism in the injured brain. Rats were either grouped into naïve controls or received lateral fluid percussion brain injury (2-2.5 atm) and followed up for 7 days. Rats were either grouped into naïve controls or received lateral fluid percussion brain injury (2-2.5 atm) and followed for 7 days. The severity of brain injury was evaluated by the neurological severity scale-revised (NSS-R) at 3 and 5 days post TBI and immunohistochemical analyses at 7 days post TBI. The expression profiles of mitochondrial-targeted genes across the hippocampus from TBI and naïe rats were also examined by oligo-DNA microarrays. NSS-R scores of TBI rats (5.4 ± 0.5) in comparison to naïe rats (3.9 ± 0.5) and H and E staining of brain sections suggested a mild brain injury. Bioinformatics and systems biology analyses showed 31 dysregulated genes, 10 affected canonical molecular pathways including a number of genes involved in mitochondrial enzymes for oxidative phosphorylation, mitogen-activated protein Kinase (MAP), peroxisome proliferator-activated protein (PPAP), apoptosis signaling, and genes responsible for long-term potentiation of Alzheimer's and Parkinson's diseases. Our results suggest that dysregulated mitochondrial-focused genes in injured brains may have a clinical utility for the development of future therapeutic strategies aimed at the treatment of TBI.

Is cell aging caused by respiration-dependent injury to the mitochondrial genome

Science.gov (United States)

Fleming, J. E.; Yengoyan, L. S.; Miquel, J.; Cottrell, S. F.; Economos, A. C.

1982-01-01

Though intrinsic mitochondrial aging has been considered before as a possible cause of cellular senescence, the mechanisms of such mitochondrial aging have remained obscure. In this article, the hypothesis of free-radical-induced inhibition of mitochondrial replenishment in fixed postmitotic cells is expanded. It is maintained that the respiration-dependent production of superoxide and hydroxyl radicals may not be fully counteracted, leading to a continuous production of lipoperoxides and malonaldehyde in actively respiring mitochondria. These compounds, in turn, can easily react with the mitochondrial DNA which is in close spatial relationship with the inner mitochondrial membrane, producing an injury that the mitochondria may be unable to counteract because of their apparent lack of adequate repair mechanisms. Mitochondrial division may thus be inhibited leading to age-related reduction of mitochondrial numbers, a deficit in energy production with a concomitant decrease in protein synthesis, deterioration of physiological performance, and, therefore, of organismic performance.

Mitochondrial events responsible for morphine's cardioprotection against ischemia/reperfusion injury

International Nuclear Information System (INIS)

He, Haiyan; Huh, Jin; Wang, Huihua; Kang, Yi; Lou, Jianshi; Xu, Zhelong

2016-01-01

Morphine may induce cardioprotection by targeting mitochondria, but little is known about the exact mitochondrial events that mediate morphine's protection. We aimed to address the role of the mitochondrial Src tyrosine kinase in morphine's protection. Isolated rat hearts were subjected to 30 min ischemia and 2 h of reperfusion. Morphine was given before the onset of ischemia. Infarct size and troponin I release were measured to evaluate cardiac injury. Oxidative stress was evaluated by measuring mitochondrial protein carbonylation and mitochondrial ROS generation. HL-1 cells were subjected to simulated ischemia/reperfusion and LDH release and mitochondrial membrane potential (ΔΨm) were measured. Morphine reduced infarct size as well as cardiac troponin I release which were aborted by the selective Src tyrosine kinase inhibitors PP2 and Src-I1. Morphine also attenuated LDH release and prevented a loss of ΔΨm at reperfusion in a Src tyrosine kinase dependent manner in HL-1 cells. However, morphine failed to reduce LDH release in HL-1 cells transfected with Src siRNA. Morphine increased mitochondrial Src phosphorylation at reperfusion and this was abrogated by PP2. Morphine attenuated mitochondrial protein carbonylation and mitochondrial superoxide generation at reperfusion through Src tyrosine kinase. The inhibitory effect of morphine on the mitochondrial complex I activity was reversed by PP2. These data suggest that morphine induces cardioprotection by preventing mitochondrial oxidative stress through mitochondrial Src tyrosine kinase. Inhibition of mitochondrial complex I at reperfusion by Src tyrosine kinase may account for the prevention of mitochondrial oxidative stress by morphine. - Highlights: • Morphine induced mito-Src phosphorylation and reduced infarct size in rat hearts. • Morphine failed to reduce I/R-induced LDH release in Src-silencing HL-1 cells. • Morphine prevented mitochondria damage caused by I/R through Src. • Morphine reduced

Selective scavenging of intra-mitochondrial superoxide corrects diclofenac-induced mitochondrial dysfunction and gastric injury: A novel gastroprotective mechanism independent of gastric acid suppression.

Science.gov (United States)

Mazumder, Somnath; De, Rudranil; Sarkar, Souvik; Siddiqui, Asim Azhar; Saha, Shubhra Jyoti; Banerjee, Chinmoy; Iqbal, Mohd Shameel; Nag, Shiladitya; Debsharma, Subhashis; Bandyopadhyay, Uday

2016-12-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat multiple inflammatory diseases and pain but severe gastric mucosal damage is the worst outcome of NSAID-therapy. Here we report that mitoTEMPO, a mitochondrially targeted superoxide (O 2 - ) scavenger protected as well as healed gastric injury induced by diclofenac (DCF), the most commonly used NSAID. Common existing therapy against gastric injury involves suppression of gastric acid secretion by proton pump inhibitors and histamine H 2 receptor antagonists; however, dyspepsia, vitamin B12 deficiency and gastric microfloral dysbalance are the major drawbacks of acid suppression. Interestingly, mitoTEMPO did not inhibit gastric acid secretion but offered gastroprotection by preventing DCF-induced generation of O 2 - due to mitochondrial respiratory chain failure and by preventing mitochondrial oxidative stress (MOS)-mediated mitopathology. MitoTEMPO even restored DCF-stimulated reduced fatty acid oxidation, mitochondrial depolarization and bioenergetic crisis in gastric mucosa. MitoTEMPO also prevented the activation of mitochondrial pathway of apoptosis and MOS-mediated proinflammatory signaling through NF-κB by DCF. Furthermore, mitoTEMPO when administered in rats with preformed gastric lesions expedited the healing of gastric injury and the healed stomach exhibited its normal physiology as evident from gastric acid and pepsin secretions under basal or stimulated conditions. Thus, in contrast to the existing antiulcer drugs, mitochondrially targeted O 2 - scavengers like mitoTEMPO may represent a novel class of gastroprotective molecules that does not affect gastric acid secretion and may be used in combination with DCF, keeping its anti-inflammatory action intact, while reducing its gastrodamaging effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Bax-mediated mitochondrial outer membrane permeabilization (MOMP), distinct from the mitochondrial permeability transition, is a key mechanism in diclofenac-induced hepatocyte injury: Multiple protective roles of cyclosporin A.

Science.gov (United States)

Siu, Woen Ping; Pun, Pamela Boon Li; Latchoumycandane, Calivarathan; Boelsterli, Urs A

2008-03-15

Diclofenac, a widely used nonsteroidal anti-inflammatory drug, has been associated with rare but severe cases of clinical hepatotoxicity. Diclofenac causes concentration-dependent cell death in human hepatocytes (after 24-48 h) by mitochondrial permeabilization via poorly defined mechanisms. To explore whether the cyclophilin D (CyD)-dependent mitochondrial permeability transition (mPT) and/or the mitochondrial outer membrane permeabilization (MOMP) was primarily involved in mediating cell death, we exposed immortalized human hepatocytes (HC-04) to apoptogenic concentrations of diclofenac (>500 microM) in the presence or absence of inhibitors of upstream mediators. The CyD inhibitor, cyclosporin A (CsA, 2 microM) fully inhibited diclofenac-induced cell injury, suggesting that mPT was involved. However, CyD gene silencing using siRNA left the cells susceptible to diclofenac toxicity, and CsA still protected the CyD-negative cells from lethal injury. Diclofenac induced early (9 h) activation of Bax and Bak and caused mitochondrial translocation of Bax, indicating that MOMP was involved in cell death. Inhibition of Bax protein expression by using siRNA significantly protected HC-04 from diclofenac-induced cell injury. Diclofenac also induced early Bid activation (tBid formation, 6 h), which is an upstream mechanism that initiates Bax activation and mitochondrial translocation. Bid activation was sensitive to the Ca2+ chelator, BAPTA. In conclusion, we found that Bax/Bak-mediated MOMP is a key mechanism of diclofenac-induced lethal cell injury in human hepatocytes, and that CsA can prevent MOMP through inhibition of Bax activation. These data support our concept that the Ca2+-Bid-Bax-MOMP axis is a critical pathway in diclofenac (metabolite)-induced hepatocyte injury.

Bax-mediated mitochondrial outer membrane permeabilization (MOMP), distinct from the mitochondrial permeability transition, is a key mechanism in diclofenac-induced hepatocyte injury: Multiple protective roles of cyclosporin A

International Nuclear Information System (INIS)

Siu, W.P.; Pun, Pamela Boon Li; Latchoumycandane, Calivarathan; Boelsterli, Urs A.

2008-01-01

Diclofenac, a widely used nonsteroidal anti-inflammatory drug, has been associated with rare but severe cases of clinical hepatotoxicity. Diclofenac causes concentration-dependent cell death in human hepatocytes (after 24-48 h) by mitochondrial permeabilization via poorly defined mechanisms. To explore whether the cyclophilin D (CyD)-dependent mitochondrial permeability transition (mPT) and/or the mitochondrial outer membrane permeabilization (MOMP) was primarily involved in mediating cell death, we exposed immortalized human hepatocytes (HC-04) to apoptogenic concentrations of diclofenac (> 500 μM) in the presence or absence of inhibitors of upstream mediators. The CyD inhibitor, cyclosporin A (CsA, 2 μM) fully inhibited diclofenac-induced cell injury, suggesting that mPT was involved. However, CyD gene silencing using siRNA left the cells susceptible to diclofenac toxicity, and CsA still protected the CyD-negative cells from lethal injury. Diclofenac induced early (9 h) activation of Bax and Bak and caused mitochondrial translocation of Bax, indicating that MOMP was involved in cell death. Inhibition of Bax protein expression by using siRNA significantly protected HC-04 from diclofenac-induced cell injury. Diclofenac also induced early Bid activation (tBid formation, 6 h), which is an upstream mechanism that initiates Bax activation and mitochondrial translocation. Bid activation was sensitive to the Ca 2+ chelator, BAPTA. In conclusion, we found that Bax/Bak-mediated MOMP is a key mechanism of diclofenac-induced lethal cell injury in human hepatocytes, and that CsA can prevent MOMP through inhibition of Bax activation. These data support our concept that the Ca 2+ -Bid-Bax-MOMP axis is a critical pathway in diclofenac (metabolite)-induced hepatocyte injury

Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury

Science.gov (United States)

Stevens, Patrick R.; Gawryluk, Jeremy W.; Hui, Liang; Chen, Xuesong; Geiger, Jonathan D.

2015-01-01

HIV-1 infected individuals are living longer but experiencing a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells leads to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat1-72-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND. PMID:25613139

PFOS prenatal exposure induce mitochondrial injury and gene expression change in hearts of weaned SD rats

International Nuclear Information System (INIS)

Xia, Wei; Wan, Yanjian; Li, Yuan-yuan; Zeng, Huaicai; Lv, Ziquan; Li, Gengqi; Wei, Zhengzheng; Xu, Shun-qing

2011-01-01

Xenobiotics exposure in early life may have adverse effects on animals' development through mitochondrial injury or dysfunction. The current study demonstrated the possibility of cardiac mitochondrial injury in prenatal PFOS-exposed weaned rat heart. Pregnant Sprague-Dawley (SD) rats were exposed to perfluorooctane sulfonate (PFOS) at doses of 0.1, 0.6 and 2.0 mg/kg/d and 0.05% Tween 80 as control by gavage from gestation days 2-21. The dams were allowed to give nature delivery and then heart tissues from weaned (postnatal day 21) offspring rats were analyzed for mitochondrial injury through ultrastructure observation by electron microscope, global gene expression profile by microarray, as well as related mRNA and proteins expression levels by quantitative PCR and western blot. Ultrastructural analysis revealed significant vacuolization and inner membrane injury occurred at the mitochondria of heart tissues from 2.0 mg/kg/d dosage group. Meanwhile, the global gene expression profile showed significant difference in level of some mRNA expression associated with mitochondrial function at 2.0 mg/kg/d dosage group, compared to the control. Furthermore, dose-response trends for the expression of selected genes were analyzed by quantitative PCR and western blot analysis. The selected genes were mainly focused on those encoding for proteins involved in energy production, control of ion levels, and maintenance of heart function. The down-regulation of mitochondrial ATP synthetase (ATP5E, ATP5I and ATP5O) implicated a decrease in energy supply. This was accompanied by down-regulation of gene transcripts involved in energy consumption such as ion transporting ATPase (ATP1A3 and ATP2B2) and inner membrane protein synthesis (SLC25A3, SLC25A4, SLC25A10, SLC25A29). The up-regulation of gene transcripts encoding for uncoupling proteins (UCP1 and UCP3), epidermal growth factor receptor (EGFR) and connective tissue growth factor (CTGF), was probably a protective process to maintain

Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1α activation following ischemia–reperfusion injury

Energy Technology Data Exchange (ETDEWEB)

Funk, Jason A., E-mail: funkj@musc.edu [Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Schnellmann, Rick G., E-mail: schnell@musc.edu [Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Ralph H. Johnson VA Medical Center, Charleston, SC 29401 (United States)

2013-12-01

Kidney ischemia–reperfusion (I/R) injury elicits cellular injury in the proximal tubule, and mitochondrial dysfunction is a pathological consequence of I/R. Promoting mitochondrial biogenesis (MB) as a repair mechanism after injury may offer a unique strategy to restore both mitochondrial and organ function. Rats subjected to bilateral renal pedicle ligation for 22 min were treated once daily with the SIRT1 activator SRT1720 (5 mg/kg) starting 24 h after reperfusion until 72 h–144 h. SIRT1 expression was elevated in the renal cortex of rats after I/R + vehicle treatment (IRV), but was associated with less nuclear localization. SIRT1 expression was even further augmented and nuclear localization was restored in the kidneys of rats after I/R + SRT1720 treatment (IRS). PGC-1α was elevated at 72 h–144 h in IRV and IRS kidneys; however, SRT1720 treatment induced deacetylation of PGC-1α, a marker of activation. Mitochondrial proteins ATP synthase β, COX I, and NDUFB8, as well as mitochondrial respiration, were diminished 24 h–144 h in IRV rats, but were partially or fully restored in IRS rats. Urinary kidney injury molecule-1 (KIM-1) was persistently elevated in both IRV and IRS rats; however, KIM-1 tissue expression was attenuated in IRS rats. Additionally, sustained loss of Na{sup +},K{sup +}–ATPase expression and basolateral localization and elevated vimentin in IRV rats was normalized in IRS rats, suggesting restoration of a differentiated, polarized tubule epithelium. The results suggest that SRT1720 treatment expedited recovery of mitochondrial protein expression and function by enhancing MB, which was associated with faster proximal tubule repair. Targeting MB may offer unique therapeutic strategy following ischemic injury. - Highlights: • We examined recovery of mitochondrial and renal function after ischemia–reperfusion. • SRT1720 treatment after I/R induced mitochondrial biogenesis via SIRT1/PGC-1α. • Recovery of mitochondrial function was

Estrogen-related receptor α is essential for maintaining mitochondrial integrity in cisplatin-induced acute kidney injury.

Science.gov (United States)

Tsushida, Keigo; Tanabe, Katsuyuki; Masuda, Kana; Tanimura, Satoshi; Miyake, Hiromasa; Arata, Yuka; Sugiyama, Hitoshi; Wada, Jun

2018-04-15

Acute kidney injury (AKI) has been associated with not only higher in-hospital mortality but also the subsequent development of chronic kidney disease (CKD). Recent evidence has suggested the involvement of mitochondrial dysfunction and impaired dynamics in the pathogenesis of AKI. Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that acts as a transcription factor to regulate the transcription of genes required for mitochondrial biogenesis and oxidative phosphorylation. In the present study, we examined the effects of ERRα deficiency on the progression of AKI induced by cisplatin. Male C57BL/6 J wild-type and ERRα -/- mice received a single intraperitoneal injection of 20 mg/kg cisplatin. Seventy-two hours after the injection, kidney function and morphology were evaluated. ERRα expression was observed in renal tubules, and cisplatin inhibited its translocation into nuclei. ERRα deficiency exacerbated cisplatin-induced renal dysfunction and tubular injury, as well as oxidative stress and apoptosis. ERRα -/- mice kidneys revealed lower mitochondrial DNA content and swollen mitochondria with reduced cristae. In addition, these mice had lower expression of the mitochondrial fusion protein mitofusin-2. The cisplatin-induced decrease in mitochondrial DNA and altered mitochondrial structure were more severe in ERRα -/- mice. In cultured mouse proximal tubular epithelial cells, the ERRα inverse agonist XCT-790 significantly inhibited mitofusin-2 expression and induced mitochondrial fragmentation. Taken together, our findings suggest the involvement of ERRα in the progression of cisplatin-induced AKI probably through impaired mitochondrial dynamics. Copyright © 2018 Elsevier Inc. All rights reserved.

Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury

Science.gov (United States)

Baburamani, Ana A.; Hurling, Chloe; Stolp, Helen; Sobotka, Kristina; Gressens, Pierre; Hagberg, Henrik; Thornton, Claire

2015-01-01

Perturbation of mitochondrial function and subsequent induction of cell death pathways are key hallmarks in neonatal hypoxic-ischemic (HI) injury, both in animal models and in term infants. Mitoprotective therapies therefore offer a new avenue for intervention for the babies who suffer life-long disabilities as a result of birth asphyxia. Here we show that after oxygen-glucose deprivation in primary neurons or in a mouse model of HI, mitochondrial protein homeostasis is altered, manifesting as a change in mitochondrial morphology and functional impairment. Furthermore we find that the mitochondrial fusion and cristae regulatory protein, OPA1, is aberrantly cleaved to shorter forms. OPA1 cleavage is normally regulated by a balanced action of the proteases Yme1L and Oma1. However, in primary neurons or after HI in vivo, protein expression of YmelL is also reduced, whereas no change is observed in Oma1 expression. Our data strongly suggest that alterations in mitochondria-shaping proteins are an early event in the pathogenesis of neonatal HI injury. PMID:26393574

Mitochondrial events responsible for morphine's cardioprotection against ischemia/reperfusion injury

Energy Technology Data Exchange (ETDEWEB)

He, Haiyan [Department of Physiology & Pathophysiology, Tianjin Medical University, Tianjin 300070 (China); Department of Pharmacology, Tianjin Medical University, Tianjin 300070 (China); Huh, Jin [Department of Anesthesia and Pain Medicine, Medical College, Kangwon National University, Chuncheon City (Korea, Republic of); Wang, Huihua [Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang Province (China); Kang, Yi; Lou, Jianshi [Department of Pharmacology, Tianjin Medical University, Tianjin 300070 (China); Xu, Zhelong, E-mail: zxu@tmu.edu.cn [Department of Physiology & Pathophysiology, Tianjin Medical University, Tianjin 300070 (China)

2016-01-01

Morphine may induce cardioprotection by targeting mitochondria, but little is known about the exact mitochondrial events that mediate morphine's protection. We aimed to address the role of the mitochondrial Src tyrosine kinase in morphine's protection. Isolated rat hearts were subjected to 30 min ischemia and 2 h of reperfusion. Morphine was given before the onset of ischemia. Infarct size and troponin I release were measured to evaluate cardiac injury. Oxidative stress was evaluated by measuring mitochondrial protein carbonylation and mitochondrial ROS generation. HL-1 cells were subjected to simulated ischemia/reperfusion and LDH release and mitochondrial membrane potential (ΔΨm) were measured. Morphine reduced infarct size as well as cardiac troponin I release which were aborted by the selective Src tyrosine kinase inhibitors PP2 and Src-I1. Morphine also attenuated LDH release and prevented a loss of ΔΨm at reperfusion in a Src tyrosine kinase dependent manner in HL-1 cells. However, morphine failed to reduce LDH release in HL-1 cells transfected with Src siRNA. Morphine increased mitochondrial Src phosphorylation at reperfusion and this was abrogated by PP2. Morphine attenuated mitochondrial protein carbonylation and mitochondrial superoxide generation at reperfusion through Src tyrosine kinase. The inhibitory effect of morphine on the mitochondrial complex I activity was reversed by PP2. These data suggest that morphine induces cardioprotection by preventing mitochondrial oxidative stress through mitochondrial Src tyrosine kinase. Inhibition of mitochondrial complex I at reperfusion by Src tyrosine kinase may account for the prevention of mitochondrial oxidative stress by morphine. - Highlights: • Morphine induced mito-Src phosphorylation and reduced infarct size in rat hearts. • Morphine failed to reduce I/R-induced LDH release in Src-silencing HL-1 cells. • Morphine prevented mitochondria damage caused by I/R through Src. • Morphine

Oxidative Damage and Mitochondrial Injuries Are Induced by Various Irrigation Pressures in Rabbit Models of Mild and Severe Hydronephrosis

Science.gov (United States)

Cao, Zhixiu; Yu, Weimin; Li, Wei; Cheng, Fan; Rao, Ting; Yao, Xiaobing; Zhang, Xiaobin; Larré, Stéphane

2015-01-01

Objective We aimed to study whether tolerance to irrigation pressure could be modified by evaluating the oxidative damage of obstructed kidneys based on rabbit models experiencing different degrees of hydronephrosis. Methods A total of 66 rabbits were randomly divided into two experimental groups and a control group. In the experimental groups, the rabbits underwent a surgical procedure inducing mild (group M, n=24) or severe (group S, n=24) hydronephrosis. In each experimental group, the rabbits were then randomly divided into 4 subgroups (M0-M3 and S0-S3) consisting of 6 rabbits each. Group 0 received no perfusion. Groups 1 through 3 were perfused with 20, 60 and 100 mmHg fluid, respectively. For the control group, after a sham operation was performed, the rabbits were divided into 4 subgroups and were perfused with fluid at 0, 20, 60 or 100 mmHg of pressure. Kidney injuries was evaluated by neutrophil gelatinase associated lipocalin (NGAL). Oxidative damage was assessed by analyzing superoxide dismutase (Mn-SOD) activity, malondialdehyde (MDA) levels, glutathione reductase (GR), catalase (CAT) and peroxide (H2O2) levels, mitochondrial injuries was assessed by mitochondrial membrane potential (MMP), the mitochondrial ultrastructure and tubular cell apoptosis. Results In the experimental groups, all results were similar for groups 0 and 1. In group 2, abnormalities were observed in the S group only, and the kidneys of rabbits in group 3 suffered oxidative damage and mitochondrial injuries with increased NGAL, decreased Mn-SOD, GR and CAT,increased MDA and H2O2, lower levels of MMP, mitochondrial vacuolization and an increased apoptotic index. Conclusion In rabbits, severely obstructed kidneys were more susceptible to oxidative damage and mitochondrial injury than mildly obstructed kidneys when subjected to higher degrees of kidney perfusion pressure. PMID:26090815

Oxidative Damage and Mitochondrial Injuries Are Induced by Various Irrigation Pressures in Rabbit Models of Mild and Severe Hydronephrosis.

Directory of Open Access Journals (Sweden)

Zhixiu Cao

Full Text Available We aimed to study whether tolerance to irrigation pressure could be modified by evaluating the oxidative damage of obstructed kidneys based on rabbit models experiencing different degrees of hydronephrosis.A total of 66 rabbits were randomly divided into two experimental groups and a control group. In the experimental groups, the rabbits underwent a surgical procedure inducing mild (group M, n=24 or severe (group S, n=24 hydronephrosis. In each experimental group, the rabbits were then randomly divided into 4 subgroups (M0-M3 and S0-S3 consisting of 6 rabbits each. Group 0 received no perfusion. Groups 1 through 3 were perfused with 20, 60 and 100 mmHg fluid, respectively. For the control group, after a sham operation was performed, the rabbits were divided into 4 subgroups and were perfused with fluid at 0, 20, 60 or 100 mmHg of pressure. Kidney injuries was evaluated by neutrophil gelatinase associated lipocalin (NGAL. Oxidative damage was assessed by analyzing superoxide dismutase (Mn-SOD activity, malondialdehyde (MDA levels, glutathione reductase (GR, catalase (CAT and peroxide (H2O2 levels, mitochondrial injuries was assessed by mitochondrial membrane potential (MMP, the mitochondrial ultrastructure and tubular cell apoptosis.In the experimental groups, all results were similar for groups 0 and 1. In group 2, abnormalities were observed in the S group only, and the kidneys of rabbits in group 3 suffered oxidative damage and mitochondrial injuries with increased NGAL, decreased Mn-SOD, GR and CAT,increased MDA and H2O2, lower levels of MMP, mitochondrial vacuolization and an increased apoptotic index.In rabbits, severely obstructed kidneys were more susceptible to oxidative damage and mitochondrial injury than mildly obstructed kidneys when subjected to higher degrees of kidney perfusion pressure.

Mitochondrial damage: An important mechanism of ambient PM2.5 exposure-induced acute heart injury in rats

International Nuclear Information System (INIS)

Li, Ruijin; Kou, Xiaojing; Geng, Hong; Xie, Jingfang; Tian, Jingjing; Cai, Zongwei; Dong, Chuan

2015-01-01

Highlights: • PM 2.5 induces heart mitochondrial morphological damage of rats. • Mitochondrial fission/fusion gene expression is important regulation mechanism. • Proinflammatoy cytokine level changes are accompanied with mitochondrial damage. • Alterations in oxidative stress and calcium homeostasis are focused on. - Abstract: Epidemiological studies suggested that ambient fine particulate matter (PM 2.5 ) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM 2.5 -induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM 2.5 with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM 2.5 exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM 2.5 exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na + K + -ATPase and Ca 2+ -ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM 2.5 -induced heart injury, and may have relations with cardiovascular disease

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism.

Science.gov (United States)

Pierce, Janet D; Gupte, Raeesa; Thimmesch, Amanda; Shen, Qiuhua; Hiebert, John B; Brooks, William M; Clancy, Richard L; Diaz, Francisco J; Harris, Janna L

2018-06-01

Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over-the-counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra-arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury-induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI. © 2018 Wiley Periodicals, Inc.

CaMKII determines mitochondrial stress responses in heart

Science.gov (United States)

Joiner, Mei-ling A.; Koval, Olha M.; Jingdong, Li; He, B. Julie; Allamargot, Chantal; Gao, Zhan; Luczak, Elizabeth D.; Hall, Duane D.; Fink, Brian D.; Chen, Biyi; Yang, Jinying; Moore, Steven A.; Scholz, Thomas D.; Strack, Stefan; Mohler, Peter J.; Sivitz, William I.; Song, Long-Sheng; Anderson, Mark E.

2012-01-01

Myocardial cell death is initiated by excessive mitochondrial Ca2+ entry, causing Ca2+ overload, mitochondrial permeability transition pore (mPTP) opening and dissipation of the mitochondrial inner membrane potential (ΔΨm)1,2. However, the signaling pathways that control mitochondrial Ca2+ entry through the inner membrane mitochondrial Ca2+ uniporter (MCU)3–5 are not known. The multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII) is activated in ischemia reperfusion (I/R), myocardial infarction (MI) and neurohumoral injury, common causes of myocardial death and heart failure, suggesting CaMKII could couple disease stress to mitochondrial injury. Here we show that CaMKII promotes mPTP opening and myocardial death by increasing MCU current (IMCU). Mitochondrial-targeted CaMKII inhibitory protein or cyclosporin A (CsA), an mPTP antagonist with clinical efficacy in I/R injury6, equivalently prevent mPTP opening, ΔΨm deterioration and diminish mitochondrial disruption and programmed cell death in response to I/R injury. Mice with myocardial and mitochondrial-targeted CaMKII inhibition are resistant to I/R injury, MI and neurohumoral injury, suggesting pathological actions of CaMKII are substantially mediated by increasing IMCU. Our findings identify CaMKII activity as a central mechanism for mitochondrial Ca2+ entry and suggest mitochondrial-targeted CaMKII inhibition could prevent or reduce myocardial death and heart failure dysfunction in response to common experimental forms of pathophysiological stress. PMID:23051746

Mitochondrial damage: An important mechanism of ambient PM{sub 2.5} exposure-induced acute heart injury in rats

Energy Technology Data Exchange (ETDEWEB)

Li, Ruijin; Kou, Xiaojing; Geng, Hong; Xie, Jingfang; Tian, Jingjing [Institute of Environmental Science, College of Environmental & Resource Sciences, Shanxi University, Taiyuan (China); Cai, Zongwei, E-mail: zwcai@hkbu.edu.hk [State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR (China); Dong, Chuan, E-mail: dc@sxu.edu.cn [Institute of Environmental Science, College of Environmental & Resource Sciences, Shanxi University, Taiyuan (China)

2015-04-28

Highlights: • PM{sub 2.5} induces heart mitochondrial morphological damage of rats. • Mitochondrial fission/fusion gene expression is important regulation mechanism. • Proinflammatoy cytokine level changes are accompanied with mitochondrial damage. • Alterations in oxidative stress and calcium homeostasis are focused on. - Abstract: Epidemiological studies suggested that ambient fine particulate matter (PM{sub 2.5}) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM{sub 2.5}-induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM{sub 2.5} with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM{sub 2.5} exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM{sub 2.5} exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na{sup +}K{sup +}-ATPase and Ca{sup 2+}-ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM{sub 2.5}-induced heart injury, and may have relations with cardiovascular disease.

Mitochondrial NUDIX hydrolases: A metabolic link between NAD catabolism, GTP and mitochondrial dynamics.

Science.gov (United States)

Long, Aaron; Klimova, Nina; Kristian, Tibor

2017-10-01

NAD + catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD + catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism. Mitochondrial and cytosolic NUDIX hydrolases (NUDT9α and NUDT9β) can affect mitochondrial and cellular AMP levels by hydrolyzing ADP- ribose (ADPr) and subsequently altering the levels of GTP and ATP. Poly (ADP-ribose) polymerase 1 (PARP1) is activated after DNA damage, which depletes NAD + pools and results in the PARylation of nuclear and mitochondrial proteins. In the mitochondria, ADP-ribosyl hydrolase-3 (ARH3) hydrolyzes PAR to ADPr, while NUDT9α metabolizes ADPr to AMP. Elevated AMP levels have been reported to reduce mitochondrial ATP production by inhibiting the adenine nucleotide translocase (ANT), allosterically activating AMPK by altering the cellular AMP: ATP ratio, and by depleting mitochondrial GTP pools by being phosphorylated by adenylate kinase 3 (AK3), which uses GTP as a phosphate donor. Recently, activated AMPK was reported to phosphorylate mitochondria fission factor (MFF), which increases Drp1 localization to the mitochondria and promotes mitochondrial fission. Moreover, the increased AK3 activity could deplete mitochondrial GTP pools and possibly inhibit normal activity of GTP-dependent fusion enzymes, thus altering mitochondrial dynamics. Published by Elsevier Ltd.

Dissociation of DNA damage and mitochondrial injury caused by hydrogen peroxide in SV-40 transformed lung epithelial cells

Directory of Open Access Journals (Sweden)

Adcock Ian M

2002-11-01

Full Text Available Abstract Background Since lung epithelial cells are constantly being exposed to reactive oxygen intermediates (ROIs, the alveolar surface is a major site of oxidative stress, and each cell type may respond differently to oxidative stress. We compared the extent of oxidative DNA damage with that of mitochondrial injury in lung epithelial cells at the single cell level. Result DNA damage and mitochondrial injury were measured after oxidative stress in the SV-40 transformed lung epithelial cell line challenged with hydrogen peroxide (H2O2. Single cell analysis of DNA damage was determined by assessing the number of 8-oxo-2-deoxyguanosine (8-oxo-dG positive cells, a marker of DNA modification, and the length of a comet tail. Mitochondrial membrane potential, ΔΨm, was determined using JC-1. A 1 h pulse of H2O2 induced small amounts of apoptosis (3%. 8-oxo-dG-positive cells and the length of the comet tail increased within 1 h of exposure to H2O2. The number of cells with reduced ΔΨm increased after the addition of H2O2 in a concentration-dependent manner. In spite of a continual loss of ΔΨm, DNA fragmentation was reduced 2 h after exposure to H2O2. Conclusion The data suggest that SV-40 transformed lung epithelial cells are resistant to oxidative stress, showing that DNA damage can be dissociated from mitochondrial injury.

Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

Directory of Open Access Journals (Sweden)

Shuai Hou

2016-05-01

Full Text Available We observed mitochondrial connexin43 (mtCx43 expression under cerebral ischemia-reperfusion (I/R injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO. Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD activity and malondialdehyde (MDA content. MtCx43, p-mtCx43, protein kinase C (PKC, and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX and diazoxide (DZX groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.

Mitochondrial abnormalities-A link to idiosyncratic drug hepatotoxicity?

International Nuclear Information System (INIS)

Boelsterli, Urs A.; Lim, Priscilla L.K.

2007-01-01

Idiosyncratic drug-induced liver injury (DILI) is a major clinical problem and poses a considerable challenge for drug development as an increasing number of successfully launched drugs or new potential drugs have been implicated in causing DILI in susceptible patient subsets. Although the incidence for a particular drug is very low (yet grossly underestimated), the outcome of DILI can be serious. Unfortunately, prediction has remained poor (both for patients at risk and for new chemical entities). The underlying mechanisms and the determinants of susceptibility have largely remained ill-defined. The aim of this review is to provide both clinical and experimental evidence for a major role of mitochondria both as a target of drugs causing idiosyncratic DILI and as mediators of delayed liver injury. We develop a unifying hypothesis that involves underlying genetic or acquired mitochondrial abnormalities as a major determinant of susceptibility for a number of drugs that target mitochondria and cause DILI. The mitochondrial hypothesis, implying gradually accumulating and initially silent mitochondrial injury in heteroplasmic cells which reaches a critical threshold and abruptly triggers liver injury, is consistent with the findings that typically idiosyncratic DILI is delayed (by weeks or months), that increasing age and female gender are risk factors and that these drugs are targeted to the liver and clearly exhibit a mitochondrial hazard in vitro and in vivo. New animal models (e.g., the Sod2 +/- mouse) provide supporting evidence for this concept. However, genetic analyses of DILI patient samples are needed to ultimately provide the proof-of-concept

Cardioprotection against ischemia/reperfusion injury by QiShenYiQi Pill® via ameliorate of multiple mitochondrial dysfunctions

Directory of Open Access Journals (Sweden)

Chen JR

2015-06-01

Full Text Available Jing Rui Chen,1–3 Jing Wei,1–3 Ling Yan Wang,1–3 Yan Zhu,1–3 Lan Li,1–3 Mary Akinyi Olunga,1–3 Xiu Mei Gao,1–3 Guan Wei Fan1–31Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, People’s Republic of China; 2Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, Ministry of Education, 3Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of ChinaAim: To investigate the potential cardioprotective effects of QiShenYiQi Pill® (QSYQ on myocardial ischemia/reperfusion (I/R injury through antioxidative stress and mitochondrial protection.Methods and results: Sprague Dawley rats were pretreated with QSYQ or saline for 7 days and subjected to ischemia (30 minutes occlusion of the left anterior descending coronary artery and reperfusion (120 minutes. Cardiac functions were evaluated by echocardiogram and hemodynamics. Myocardial mitochondria were obtained to evaluate changes in mitochondrial structure and function, immediately after 120 minutes reperfusion. Pretreatment with QSYQ protected against I/R-induced myocardial structural injury and improved cardiac hemodynamics, as demonstrated by normalized serum creatine kinase and suppressed oxidative stress. Moreover, the impaired myocardial mitochondrial structure and function decreased level of ATP (accompanied by reduction of ATP5D and increase in the expression of cytochrome C. Myocardial fiber rupture, interstitial edema, and infiltrated leukocytes were all significantly ameliorated by pretreatment with QSYQ.Conclusion: Pretreatment of QSYQ in Sprague Dawley rats improves ventricular function and energy metabolism and reduces oxidative stress via ameliorating multiple mitochondrial dysfunctions during I/R injury.Keywords: QSYQ, ischemia/reperfusion injury, energy metabolism, mitochondria

The axon-protective WLD(S) protein partially rescues mitochondrial respiration and glycolysis after axonal injury.

Science.gov (United States)

Godzik, Katharina; Coleman, Michael P

2015-04-01

The axon-protective Wallerian degeneration slow (WLD(S)) protein can ameliorate the decline in axonal ATP levels after neurite transection. Here, we tested the hypothesis that this effect is associated with maintenance of mitochondrial respiration and/or glycolysis. We used isolated neurites of superior cervical ganglion (SCG) cultures in the Seahorse XF-24 Metabolic Flux Analyser to determine mitochondrial respiration and glycolysis under different conditions. We observed that both mitochondrial respiration and glycolysis declined significantly during the latent phase of Wallerian degeneration. WLD(S) partially reduced the decline both in glycolysis and in mitochondrial respiration. In addition, we found that depleting NAD levels in uncut cultures led to changes in mitochondrial respiration and glycolysis similar to those rescued by WLD(S) after cut, suggesting that the maintenance of NAD levels in Wld(S) neurites after axonal injury at least partially underlies the maintenance of ATP levels. However, by using another axon-protective mutation (Sarm1(-/-)), we could demonstrate that rescue of basal ECAR (and hence probably glycolysis) rather than basal OCR (mitochondrial respiration) may be part of the protective phenotype to delay Wallerian degeneration. These findings open new routes to study glycolysis and the connection between NAD and ATP levels in axon degeneration, which may help to eventually develop therapeutic strategies to treat neurodegenerative diseases.

Leflunomide or A77 1726 protect from acetaminophen-induced cell injury through inhibition of JNK-mediated mitochondrial permeability transition in immortalized human hepatocytes

International Nuclear Information System (INIS)

Latchoumycandane, Calivarathan; Seah, Quee Ming; Tan, Rachel C.H.; Sattabongkot, Jetsumon; Beerheide, Walter; Boelsterli, Urs A.

2006-01-01

Leflunomide, a disease-modifying anti-rheumatic drug, protects against T-cell-mediated liver injury by poorly understood mechanisms. The active metabolite of leflunomide, A77 1726 (teriflunomide) has been shown to inhibit stress-activated protein kinases (JNK pathway), which are key regulators of mitochondria-mediated cell death. Therefore, we hypothesized that leflunomide may protect from drugs that induce the mitochondrial permeability transition (mPT) by blocking the JNK signaling pathway. To this end, we exposed cultured immortalized human hepatocytes (HC-04) to the standard protoxicant drug acetaminophen (APAP), which induces CsA-sensitive mPT-mediated cell death. We determined the effects of leflunomide on the extent of APAP-induced hepatocyte injury and the upstream JNK-mediated mitochondrial signaling pathways. We found that leflunomide or A77 1726 concentration-dependently protected hepatocytes from APAP (1 mM)-induced mitochondrial permeabilization and lethal cell injury. This was not due to proximal inhibition of CYP-catalyzed APAP bioactivation to its thiol-reactive metabolite. Instead, we demonstrate that leflunomide (20 μM) inhibited the APAP-induced early (3 h) activation (phosphorylation) of JNK1/2, thus inhibiting phosphorylation of the anti-apoptotic protein Bcl-2 and preventing P-Bcl-2-mediated induction of the mPT. This greatly attenuated mitochondrial cytochrome c release, which we used as a marker for mitochondrial permeabilization. The specific JNK2 inhibitor SP600125 similarly protected from APAP-induced cell death. In conclusion, these findings are consistent with our hypothesis that leflunomide protects from protoxicant-induced hepatocyte injury by inhibiting JNK signaling and preventing mPT induction

Lightning injury: a review.

Science.gov (United States)

Ritenour, Amber E; Morton, Melinda J; McManus, John G; Barillo, David J; Cancio, Leopoldo C

2008-08-01

Lightning is an uncommon but potentially devastating cause of injury in patients presenting to burn centers. These injuries feature unusual symptoms, high mortality, and significant long-term morbidity. This paper will review the epidemiology, physics, clinical presentation, management principles, and prevention of lightning injuries.

Mountain biking injuries: a review.

Science.gov (United States)

Carmont, Michael R

2008-01-01

Mountain biking is a fast, exciting adventure sport with increasing numbers of participants and competitions. A search of PubMed, Medline, CINAHL, DH data, and Embase databases was performed using the following keywords: mountain, biking and injuries. This revealed 2 review articles, 17 case controlled studies, 4 case series and 5 case reports. This review summarises the published literature on mountain biking injuries, discusses injury frequency and common injury mechanisms. Riders are quick to adopt safety measures. Helmet usage is now increasingly common and handlebar adaptations have been discontinued. Although the sport has a reputation for speed and risk with research and awareness, injury prevention measures are being adopted making the sport as safe as possible.

Over-expression of mitochondrial creatine kinase in the murine heart improves functional recovery and protects against injury following ischaemia-reperfusion.

Science.gov (United States)

Whittington, Hannah J; Ostrowski, Philip J; McAndrew, Debra J; Cao, Fang; Shaw, Andrew; Eykyn, Thomas R; Lake, Hannah; Tyler, Jack; Schneider, Jurgen E; Neubauer, Stefan; Zervou, Sevasti; Lygate, Craig A

2018-03-02

Mitochondrial creatine kinase (MtCK) couples ATP production via oxidative phosphorylation to phosphocreatine in the cytosol, which acts as a mobile energy store available for regeneration of ATP at times of high demand. We hypothesised that elevating MtCK would be beneficial in ischaemia-reperfusion (I/R) injury. Mice were created overexpressing the sarcomeric MtCK gene with αMHC promoter at the Rosa26 locus (MtCK-OE) and compared with wild-type (WT) littermates. MtCK activity was 27% higher than WT, with no change in other CK isoenzymes or creatine levels. Electron microscopy confirmed normal mitochondrial cell density and mitochondrial localisation of transgenic protein. Respiration in isolated mitochondria was unaltered and metabolomic analysis by 1H-NMR suggests that cellular metabolism was not grossly affected by transgene expression. There were no significant differences in cardiac structure or function under baseline conditions by cine-MRI or LV haemodynamics. In Langendorff-perfused hearts subjected to 20min ischaemia and 30 min reperfusion, MtCK-OE exhibited less ischaemic contracture and improved functional recovery (Rate pressure product 58% above WT; P < 0.001). These hearts had reduced myocardial infarct size, which was confirmed in vivo: 55±4% in WT vs 29±4% in MtCK-OE; P < 0.0001). Isolated cardiomyocytes from MtCK-OE hearts exhibited delayed opening of the mitochondrial permeability transition pore (mPTP) compared to WT, which was confirmed by reduced mitochondrial swelling in response to calcium. There was no detectable change in the structural integrity of the mitochondrial membrane. Modest elevation of MtCK activity in the heart does not adversely affect cellular metabolism, mitochondrial or in vivo cardiac function, but modifies mPTP opening to protect against I/R injury and improve functional recovery. Our findings support MtCK as a prime therapeutic target in myocardial ischaemia.

Mitochondrial Disease

OpenAIRE

Bulent Kurt; Turgut Topal

2013-01-01

Mitochondria are the major energy source of cells. Mitochondrial disease occurs due to a defect in mitochondrial energy production. A valuable energy production in mitochondria depend a healthy interconnection between nuclear and mitochondrial DNA. A mutation in nuclear or mitochondrial DNA may cause abnormalities in ATP production and single or multiple organ dysfunctions, secondarily. In this review, we summarize mitochondrial physiology, mitochondrial genetics, and clinical expression and ...

Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1.

Science.gov (United States)

Yang, Long; Xie, Peng; Wu, Jianjiang; Yu, Jin; Yu, Tian; Wang, Haiying; Wang, Jiang; Xia, Zhengyuan; Zheng, Hong

2016-01-01

Sevoflurane postconditioning (SPostC) can exert myocardial protective effects similar to ischemic preconditioning. However, the exact myocardial protection mechanism by SPostC is unclear. Studies indicate that hypoxia-inducible factor-1 (HIF-1) maintains cellular respiration homeostasis by regulating mitochondrial respiratory chain enzyme activity under hypoxic conditions. This study investigated whether SPostC could regulate the expression of myocardial HIF-1α and to improve mitochondrial respiratory function, thereby relieving myocardial ischemia-reperfusion injury in rats. The myocardial ischemia-reperfusion rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, postconditioning was performed using sevoflurane alone or in combination with the HIF-1α inhibitor 2-methoxyestradiol (2ME2). The changes in hemodynamic parameters, HIF-1α protein expression levels, mitochondrial respiratory function and enzyme activity, mitochondrial reactive oxygen species (ROS) production rates, and mitochondrial ultrastructure were measured or observed. Compared to the ischemia-reperfusion (I/R) group, HIF-1α expression in the SPostC group was significantly up-regulated. Additionally, cardiac function indicators, mitochondrial state 3 respiratory rate, respiratory control ratio (RCR), cytochrome C oxidase (C c O), NADH oxidase (NADHO), and succinate oxidase (SUCO) activities, mitochondrial ROS production rate, and mitochondrial ultrastructure were significantly better than those in the I/R group. However, these advantages were completely reversed by the HIF-1α specific inhibitor 2ME2 ( P <0.05). The myocardial protective function of SPostC might be associated with the improvement of mitochondrial respiratory function after up-regulation of HIF-1α expression.

High-throughput respirometric assay identifies predictive toxicophore of mitochondrial injury

Energy Technology Data Exchange (ETDEWEB)

Wills, Lauren P. [MitoHealth Inc., Charleston, SC 29403 (United States); Beeson, Gyda C.; Trager, Richard E.; Lindsey, Christopher C. [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Beeson, Craig C. [MitoHealth Inc., Charleston, SC 29403 (United States); Peterson, Yuri K. [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Schnellmann, Rick G., E-mail: schnell@musc.edu [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Ralph H. Johnson VA Medical Center, Charleston, SC 29401 (United States)

2013-10-15

Many environmental chemicals and drugs negatively affect human health through deleterious effects on mitochondrial function. Currently there is no chemical library of mitochondrial toxicants, and no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct chemical entities can identify previously unidentified mitochondrial toxicants. We used a respirometric assay to screen 1760 compounds (5 μM) from the LOPAC and ChemBridge DIVERSet libraries. Thirty-one of the assayed compounds decreased uncoupled respiration, a stress test for mitochondrial dysfunction, prior to a decrease in cell viability and reduced the oxygen consumption rate in isolated mitochondria. The mitochondrial toxicants were grouped by chemical similarity and two clusters containing four compounds each were identified. Cheminformatic analysis of one of the clusters identified previously uncharacterized mitochondrial toxicants from the ChemBridge DIVERSet. This approach will enable the identification of mitochondrial toxicants and advance the prediction of mitochondrial toxicity for both drug discovery and risk assessment. - Highlights: • Respirometric assay conducted in RPTC to create mitochondrial toxicant database. • Chemically similar mitochondrial toxicants aligned as mitochondrial toxicophores • Mitochondrial toxicophore identifies five novel mitochondrial toxicants.

High-throughput respirometric assay identifies predictive toxicophore of mitochondrial injury

International Nuclear Information System (INIS)

Wills, Lauren P.; Beeson, Gyda C.; Trager, Richard E.; Lindsey, Christopher C.; Beeson, Craig C.; Peterson, Yuri K.; Schnellmann, Rick G.

2013-01-01

Many environmental chemicals and drugs negatively affect human health through deleterious effects on mitochondrial function. Currently there is no chemical library of mitochondrial toxicants, and no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct chemical entities can identify previously unidentified mitochondrial toxicants. We used a respirometric assay to screen 1760 compounds (5 μM) from the LOPAC and ChemBridge DIVERSet libraries. Thirty-one of the assayed compounds decreased uncoupled respiration, a stress test for mitochondrial dysfunction, prior to a decrease in cell viability and reduced the oxygen consumption rate in isolated mitochondria. The mitochondrial toxicants were grouped by chemical similarity and two clusters containing four compounds each were identified. Cheminformatic analysis of one of the clusters identified previously uncharacterized mitochondrial toxicants from the ChemBridge DIVERSet. This approach will enable the identification of mitochondrial toxicants and advance the prediction of mitochondrial toxicity for both drug discovery and risk assessment. - Highlights: • Respirometric assay conducted in RPTC to create mitochondrial toxicant database. • Chemically similar mitochondrial toxicants aligned as mitochondrial toxicophores • Mitochondrial toxicophore identifies five novel mitochondrial toxicants

Creatine Enhances Mitochondrial-Mediated Oligodendrocyte Survival After Demyelinating Injury.

Science.gov (United States)

Chamberlain, Kelly A; Chapey, Kristen S; Nanescu, Sonia E; Huang, Jeffrey K

2017-02-08

Chronic oligodendrocyte loss, which occurs in the demyelinating disorder multiple sclerosis (MS), contributes to axonal dysfunction and neurodegeneration. Current therapies are able to reduce MS severity, but do not prevent transition into the progressive phase of the disease, which is characterized by chronic neurodegeneration. Therefore, pharmacological compounds that promote oligodendrocyte survival could be beneficial for neuroprotection in MS. Here, we investigated the role of creatine, an organic acid involved in adenosine triphosphate (ATP) buffering, in oligodendrocyte function. We found that creatine increased mitochondrial ATP production directly in oligodendrocyte lineage cell cultures and exerted robust protection on oligodendrocytes by preventing cell death in both naive and lipopolysaccharide-treated mixed glia. Moreover, lysolecithin-mediated demyelination in mice deficient in the creatine-synthesizing enzyme guanidinoacetate-methyltransferase ( Gamt ) did not affect oligodendrocyte precursor cell recruitment, but resulted in exacerbated apoptosis of regenerated oligodendrocytes in central nervous system (CNS) lesions. Remarkably, creatine administration into Gamt -deficient and wild-type mice with demyelinating injury reduced oligodendrocyte apoptosis, thereby increasing oligodendrocyte density and myelin basic protein staining in CNS lesions. We found that creatine did not affect the recruitment of macrophages/microglia into lesions, suggesting that creatine affects oligodendrocyte survival independently of inflammation. Together, our results demonstrate a novel function for creatine in promoting oligodendrocyte viability during CNS remyelination. SIGNIFICANCE STATEMENT We report that creatine enhances oligodendrocyte mitochondrial function and protects against caspase-dependent oligodendrocyte apoptosis during CNS remyelination. This work has important implications for the development of therapeutic targets for diseases characterized by

Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury

Directory of Open Access Journals (Sweden)

Bryan Leaw

2017-07-01

Full Text Available Injury to the fragile immature brain is implicated in the manifestation of long-term neurological disorders, including childhood disability such as cerebral palsy, learning disability and behavioral disorders. Advancements in perinatal practice and improved care mean the majority of infants suffering from perinatal brain injury will survive, with many subtle clinical symptoms going undiagnosed until later in life. Hypoxic-ischemia is the dominant cause of perinatal brain injury, and constitutes a significant socioeconomic burden to both developed and developing countries. Therapeutic hypothermia is the sole validated clinical intervention to perinatal asphyxia; however it is not always neuroprotective and its utility is limited to developed countries. There is an urgent need to better understand the molecular pathways underlying hypoxic-ischemic injury to identify new therapeutic targets in such a small but critical therapeutic window. Mitochondria are highly implicated following ischemic injury due to their roles as the powerhouse and main energy generators of the cell, as well as cell death processes. While the link between impaired mitochondrial bioenergetics and secondary energy failure following loss of high-energy phosphates is well established after hypoxia-ischemia (HI, there is emerging evidence that the roles of mitochondria in disease extend far beyond this. Indeed, mitochondrial turnover, including processes such as mitochondrial biogenesis, fusion, fission and mitophagy, affect recovery of neurons after injury and mitochondria are involved in the regulation of the innate immune response to inflammation. This review article will explore these mitochondrial pathways, and finally will summarize past and current efforts in targeting these pathways after hypoxic-ischemic injury, as a means of identifying new avenues for clinical intervention.

Altering CO2 during reperfusion of ischemic cardiomyocytes modifies mitochondrial oxidant injury.

Science.gov (United States)

Lavani, Romeen; Chang, Wei-Tien; Anderson, Travis; Shao, Zuo-Hui; Wojcik, Kimberly R; Li, Chang-Qing; Pietrowski, Robert; Beiser, David G; Idris, Ahamed H; Hamann, Kimm J; Becker, Lance B; Vanden Hoek, Terry L

2007-07-01

Acute changes in tissue CO2 and pH during reperfusion of the ischemic heart may affect ischemia/reperfusion injury. We tested whether gradual vs. acute decreases in CO2 after cardiomyocyte ischemia affect reperfusion oxidants and injury. Comparative laboratory investigation. Institutional laboratory. Embryonic chick cardiomyocytes. Microscope fields of approximately 500 chick cardiomyocytes were monitored throughout 1 hr of simulated ischemia (PO2 of 3-5 torr, PCO2 of 144 torr, pH 6.8), followed by 3 hrs of reperfusion (PO2 of 149 torr, PCO2 of 36 torr, pH 7.4), and compared with cells reperfused with relative hypercarbia (PCO2 of 71 torr, pH 6.8) or hypocarbia (PCO2 of 7 torr, pH 7.9). The measured outcomes included cell viability (via propidium iodide) and oxidant generation (reactive oxygen species via 2',7'-dichlorofluorescin oxidation and nitric oxide [NO] via 4,5-diaminofluorescein diacetate oxidation). Compared with normocarbic reperfusion, hypercarbia significantly reduced cell death from 54.8% +/- 4.0% to 26.3% +/- 2.8% (p < .001), significantly decreased reperfusion reactive oxygen species (p < .05), and increased NO at a later phase of reperfusion (p < .01). The NO synthase inhibitor N-nitro-L-arginine methyl ester (200 microM) reversed this oxidant attenuation (p < .05), NO increase (p < .05), and the cardioprotection conferred by hypercarbic reperfusion (increasing death to 54.3% +/- 6.0% [p < .05]). Conversely, hypocarbic reperfusion increased cell death to 80.4% +/- 4.5% (p < .01). It also increased reactive oxygen species by almost two-fold (p = .052), without affecting the NO level thereafter. Increased reactive oxygen species was attenuated by the mitochondrial complex III inhibitor stigmatellin (20 nM) when given at reperfusion (p < .05). Cell death also decreased from 85.9% +/- 4.5% to 52.2% +/- 6.5% (p < .01). The nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin (300 microM) had no effect on reperfusion reactive oxygen

Acetaminophen-induced liver injury in rats and mice: Comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity

International Nuclear Information System (INIS)

McGill, Mitchell R.; Williams, C. David; Xie, Yuchao; Ramachandran, Anup; Jaeschke, Hartmut

2012-01-01

Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the West. In mice, APAP hepatotoxicity can be rapidly induced with a single dose. Because it is both clinically relevant and experimentally convenient, APAP intoxication has become a popular model of liver injury. Early data demonstrated that rats are resistant to APAP toxicity. As a result, mice are the preferred species for mechanistic studies. Furthermore, recent work has shown that the mechanisms of APAP toxicity in humans are similar to mice. Nevertheless, some investigators still use rats. New mechanistic information from the last forty years invites a reevaluation of the differences between these species. Comparison may provide interesting insights and confirm or exclude the rat as an option for APAP studies. To this end, we treated rats and mice with APAP and measured parameters of liver injury, APAP metabolism, oxidative stress, and activation of the c-Jun N-terminal kinase (JNK). Consistent with earlier data, we found that rats were highly resistant to APAP toxicity. Although overall APAP metabolism was similar in both species, mitochondrial protein adducts were significantly lower in rats. Accordingly, rats also had less oxidative stress. Finally, while mice showed extensive activation and mitochondrial translocation of JNK, this could not be detected in rat livers. These data support the hypothesis that mitochondrial dysfunction is critical for the development of necrosis after APAP treatment. Because mitochondrial damage also occurs in humans, rats are not a clinically relevant species for studies of APAP hepatotoxicity. Highlights: ► Acetaminophen overdose causes severe liver injury only in mice but not in rats. ► APAP causes hepatic GSH depletion and protein adduct formation in rats and mice. ► Less protein adducts were measured in rat liver mitochondria compared to mouse. ► No oxidant stress, peroxynitrite formation or JNK activation was present in rats. ► The

Cdk1, PKCδ and calcineurin-mediated Drp1 pathway contributes to mitochondrial fission-induced cardiomyocyte death

International Nuclear Information System (INIS)

Zaja, Ivan; Bai, Xiaowen; Liu, Yanan; Kikuchi, Chika; Dosenovic, Svjetlana; Yan, Yasheng; Canfield, Scott G.; Bosnjak, Zeljko J.

2014-01-01

Highlights: • Drp1-mediated increased mitochondrial fission but not fusion is involved the cardiomyocyte death during anoxia-reoxygenation injury. • Reactive oxygen species are upstream initiators of mitochondrial fission. • Increased mitochondrial fission is resulted from Cdk1-, PKCδ-, and calcineurin-mediated Drp1 pathways. - Abstract: Myocardial ischemia–reperfusion (I/R) injury is one of the leading causes of death and disability worldwide. Mitochondrial fission has been shown to be involved in cardiomyocyte death. However, molecular machinery involved in mitochondrial fission during I/R injury has not yet been completely understood. In this study we aimed to investigate molecular mechanisms of controlling activation of dynamin-related protein 1 (Drp1, a key protein in mitochondrial fission) during anoxia-reoxygenation (A/R) injury of HL1 cardiomyocytes. A/R injury induced cardiomyocyte death accompanied by the increases of mitochondrial fission, reactive oxygen species (ROS) production and activated Drp1 (pSer616 Drp1), and decrease of inactivated Drp1 (pSer637 Drp1) while mitochondrial fusion protein levels were not significantly changed. Blocking Drp1 activity with mitochondrial division inhibitor mdivi1 attenuated cell death, mitochondrial fission, and Drp1 activation after A/R. Trolox, a ROS scavenger, decreased pSer616 Drp1 level and mitochondrial fission after A/R. Immunoprecipitation assay further indicates that cyclin dependent kinase 1 (Cdk1) and protein kinase C isoform delta (PKCδ) bind Drp1, thus increasing mitochondrial fission. Inhibiting Cdk1 and PKCδ attenuated the increases in pSer616 Drp1, mitochondrial fission, and cardiomyocyte death. FK506, a calcineurin inhibitor, blocked the decrease in expression of inactivated pSer637 Drp1 and mitochondrial fission. Our findings reveal the following novel molecular mechanisms controlling mitochondrial fission during A/R injury of cardiomyocytes: (1) ROS are upstream initiators of

Cdk1, PKCδ and calcineurin-mediated Drp1 pathway contributes to mitochondrial fission-induced cardiomyocyte death

Energy Technology Data Exchange (ETDEWEB)

Zaja, Ivan [Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Bai, Xiaowen, E-mail: xibai@mcw.edu [Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Liu, Yanan; Kikuchi, Chika; Dosenovic, Svjetlana; Yan, Yasheng; Canfield, Scott G. [Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Bosnjak, Zeljko J. [Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States)

2014-10-31

Highlights: • Drp1-mediated increased mitochondrial fission but not fusion is involved the cardiomyocyte death during anoxia-reoxygenation injury. • Reactive oxygen species are upstream initiators of mitochondrial fission. • Increased mitochondrial fission is resulted from Cdk1-, PKCδ-, and calcineurin-mediated Drp1 pathways. - Abstract: Myocardial ischemia–reperfusion (I/R) injury is one of the leading causes of death and disability worldwide. Mitochondrial fission has been shown to be involved in cardiomyocyte death. However, molecular machinery involved in mitochondrial fission during I/R injury has not yet been completely understood. In this study we aimed to investigate molecular mechanisms of controlling activation of dynamin-related protein 1 (Drp1, a key protein in mitochondrial fission) during anoxia-reoxygenation (A/R) injury of HL1 cardiomyocytes. A/R injury induced cardiomyocyte death accompanied by the increases of mitochondrial fission, reactive oxygen species (ROS) production and activated Drp1 (pSer616 Drp1), and decrease of inactivated Drp1 (pSer637 Drp1) while mitochondrial fusion protein levels were not significantly changed. Blocking Drp1 activity with mitochondrial division inhibitor mdivi1 attenuated cell death, mitochondrial fission, and Drp1 activation after A/R. Trolox, a ROS scavenger, decreased pSer616 Drp1 level and mitochondrial fission after A/R. Immunoprecipitation assay further indicates that cyclin dependent kinase 1 (Cdk1) and protein kinase C isoform delta (PKCδ) bind Drp1, thus increasing mitochondrial fission. Inhibiting Cdk1 and PKCδ attenuated the increases in pSer616 Drp1, mitochondrial fission, and cardiomyocyte death. FK506, a calcineurin inhibitor, blocked the decrease in expression of inactivated pSer637 Drp1 and mitochondrial fission. Our findings reveal the following novel molecular mechanisms controlling mitochondrial fission during A/R injury of cardiomyocytes: (1) ROS are upstream initiators of

Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter

International Nuclear Information System (INIS)

Schwartz, Justin; Holmuhamedov, Ekhson; Zhang, Xun; Lovelace, Gregory L.; Smith, Charles D.; Lemasters, John J.

2013-01-01

Minocycline, a tetracycline-derived compound, mitigates damage caused by ischemia/reperfusion (I/R) injury. Here, 19 tetracycline-derived compounds were screened in comparison to minocycline for their ability to protect hepatocytes against damage from chemical hypoxia and I/R injury. Cultured rat hepatocytes were incubated with 50 μM of each tetracycline-derived compound 20 min prior to exposure to 500 μM iodoacetic acid plus 1 mM KCN (chemical hypoxia). In other experiments, hepatocytes were incubated in anoxic Krebs–Ringer–HEPES buffer at pH 6.2 for 4 h prior to reoxygenation at pH 7.4 (simulated I/R). Tetracycline-derived compounds were added 20 min prior to reperfusion. Ca 2+ uptake was measured in isolated rat liver mitochondria incubated with Fluo-5N. Cell killing after 120 min of chemical hypoxia measured by propidium iodide (PI) fluorometry was 87%, which decreased to 28% and 42% with minocycline and doxycycline, respectively. After I/R, cell killing at 120 min decreased from 79% with vehicle to 43% and 49% with minocycline and doxycycline. No other tested compound decreased killing. Minocycline and doxycycline also inhibited mitochondrial Ca 2+ uptake and suppressed the Ca 2+ -induced mitochondrial permeability transition (MPT), the penultimate cause of cell death in reperfusion injury. Ru360, a specific inhibitor of the mitochondrial calcium uniporter (MCU), also decreased cell killing after hypoxia and I/R and blocked mitochondrial Ca 2+ uptake and the MPT. Other proposed mechanisms, including mitochondrial depolarization and matrix metalloprotease inhibition, could not account for cytoprotection. Taken together, these results indicate that minocycline and doxycycline are cytoprotective by way of inhibition of MCU. - Highlights: • Minocycline and doxycycline are the only cytoprotective tetracyclines of those tested • Cytoprotective tetracyclines inhibit the MPT and mitochondrial calcium and iron uptake. • Cytoprotective tetracyclines protect

Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter

Energy Technology Data Exchange (ETDEWEB)

Schwartz, Justin; Holmuhamedov, Ekhson; Zhang, Xun; Lovelace, Gregory L.; Smith, Charles D. [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC (United States); Lemasters, John J., E-mail: JJLemasters@musc.edu [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC (United States); Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC (United States)

2013-11-15

Minocycline, a tetracycline-derived compound, mitigates damage caused by ischemia/reperfusion (I/R) injury. Here, 19 tetracycline-derived compounds were screened in comparison to minocycline for their ability to protect hepatocytes against damage from chemical hypoxia and I/R injury. Cultured rat hepatocytes were incubated with 50 μM of each tetracycline-derived compound 20 min prior to exposure to 500 μM iodoacetic acid plus 1 mM KCN (chemical hypoxia). In other experiments, hepatocytes were incubated in anoxic Krebs–Ringer–HEPES buffer at pH 6.2 for 4 h prior to reoxygenation at pH 7.4 (simulated I/R). Tetracycline-derived compounds were added 20 min prior to reperfusion. Ca{sup 2+} uptake was measured in isolated rat liver mitochondria incubated with Fluo-5N. Cell killing after 120 min of chemical hypoxia measured by propidium iodide (PI) fluorometry was 87%, which decreased to 28% and 42% with minocycline and doxycycline, respectively. After I/R, cell killing at 120 min decreased from 79% with vehicle to 43% and 49% with minocycline and doxycycline. No other tested compound decreased killing. Minocycline and doxycycline also inhibited mitochondrial Ca{sup 2+} uptake and suppressed the Ca{sup 2+}-induced mitochondrial permeability transition (MPT), the penultimate cause of cell death in reperfusion injury. Ru360, a specific inhibitor of the mitochondrial calcium uniporter (MCU), also decreased cell killing after hypoxia and I/R and blocked mitochondrial Ca{sup 2+} uptake and the MPT. Other proposed mechanisms, including mitochondrial depolarization and matrix metalloprotease inhibition, could not account for cytoprotection. Taken together, these results indicate that minocycline and doxycycline are cytoprotective by way of inhibition of MCU. - Highlights: • Minocycline and doxycycline are the only cytoprotective tetracyclines of those tested • Cytoprotective tetracyclines inhibit the MPT and mitochondrial calcium and iron uptake. • Cytoprotective

Mitochondrial Dynamics: Coupling Mitochondrial Fitness with Healthy Aging.

Science.gov (United States)

Sebastián, David; Palacín, Manuel; Zorzano, Antonio

2017-03-01

Aging is associated with a decline in mitochondrial function and the accumulation of abnormal mitochondria. However, the precise mechanisms by which aging promotes these mitochondrial alterations and the role of the latter in aging are still not fully understood. Mitochondrial dynamics is a key process regulating mitochondrial function and quality. Altered expression of some mitochondrial dynamics proteins has been recently associated with aging and with age-related alterations in yeast, Caenorhabditis elegans, mice, and humans. Here, we review the link between alterations in mitochondrial dynamics, aging, and age-related impairment. We propose that the dysregulation of mitochondrial dynamics leads to age-induced accumulation of unhealthy mitochondria and contributes to alterations linked to aging, such as diabetes and neurodegeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regenerative abilities of mesenchymal stem cells through mitochondrial transfer.

Science.gov (United States)

Paliwal, Swati; Chaudhuri, Rituparna; Agrawal, Anurag; Mohanty, Sujata

2018-03-30

The past decade has witnessed an upsurge in studies demonstrating mitochondrial transfer as one of the emerging mechanisms through which mesenchymal stem cells (MSCs) can regenerate and repair damaged cells or tissues. It has been found to play a critical role in healing several diseases related to brain injury, cardiac myopathies, muscle sepsis, lung disorders and acute respiratory disorders. Several studies have shown that various mechanisms are involved in mitochondrial transfer that includes tunnel tube formation, micro vesicle formation, gap junctions, cell fusion and others modes of transfer. Few studies have investigated the mechanisms that contribute to mitochondrial transfer, primarily comprising of signaling pathways involved in tunnel tube formation that facilitates tunnel tube formation for movement of mitochondria from one cell to another. Various stress signals such as release of damaged mitochondria, mtDNA and mitochondrial products along with elevated reactive oxygen species levels trigger the transfer of mitochondria from MSCs to recipient cells. However, extensive cell signaling pathways that lead to mitochondrial transfer from healthy cells are still under investigation and the changes that contribute to restoration of mitochondrial bioenergetics in recipient cells remain largely elusive. In this review, we have discussed the phenomenon of mitochondrial transfer from MSCs to neighboring stressed cells, and how this aids in cellular repair and regeneration of different organs such as lung, heart, eye, brain and kidney. The potential scope of mitochondrial transfer in providing novel therapeutic strategies for treatment of various pathophysiological conditions has also been discussed.

Altered Mitochondrial Dynamics and TBI Pathophysiology

Directory of Open Access Journals (Sweden)

Tara Diane Fischer

2016-03-01

Full Text Available Mitochondrial function is intimately linked to cellular survival, growth, and death. Mitochondria not only generate ATP from oxidative phosphorylation, but also mediate intracellular calcium buffering, generation of reactive oxygen species (ROS, and apoptosis. Electron leakage from the electron transport chain, especially from damaged or depolarized mitochondria, can generate excess free radicals that damage cellular proteins, DNA, and lipids. Furthermore, mitochondrial damage releases pro-apoptotic factors to initiate cell death. Previous studies have reported that traumatic brain injury (TBI reduces mitochondrial respiration, enhances production of ROS, and triggers apoptotic cell death, suggesting a prominent role of mitochondria in TBI pathophysiology. Mitochondria maintain cellular energy homeostasis and health via balanced processes of fusion and fission, continuously dividing and fusing to form an interconnected network throughout the cell. An imbalance of these processes, particularly an excess of fission, can be detrimental to mitochondrial function, causing decreased respiration, ROS production, and apoptosis. Mitochondrial fission is regulated by the cytosolic GTPase, dynamin-related protein 1 (Drp1, which translocates to the mitochondrial outer membrane to initiate fission. Aberrant Drp1 activity has been linked to excessive mitochondrial fission and neurodegeneration. Measurement of Drp1 levels in purified hippocampal mitochondria showed an increase in TBI animals as compared to sham controls. Analysis of cryo-electron micrographs of these mitochondria also showed that TBI caused an initial increase in the length of hippocampal mitochondria at 24 hours post-injury, followed by a significant decrease in length at 72 hours. Post-TBI administration of Mdivi-1, a pharmacological inhibitor of Drp1, prevented this decrease in mitochondria length. Mdivi-1 treatment also reduced the loss of newborn neurons in the hippocampus and improved

Mitochondrial role in cell aging

Science.gov (United States)

Miquel, J.; Fleming, J.; Economos, A. C.; Johnson, J. E., Jr.

1980-01-01

The experimental studies on the mitochondria of insect and mammalian cells are examined with a view to an analysis of intrinsic mitochondrial senescence, and its relation to the age-related changes in other cell organelles. The fine structural and biochemical data support the concept that the mitochondria of fixed postmitotic cells may be the site of intrinsic aging because of the attack by free radicals and lipid peroxides originating in the organelles as a by-product of oxygen reduction during respiration. Although the cells have numerous mechanisms for counteracting lipid peroxidation injury, there is a slippage in the antioxidant protection. Intrinsic mitochondrial aging could thus be considered as a specific manifestation of oxygen toxicity. It is proposed that free radical injury renders an increasing number of the mitochondria unable to divide, probably because of damage to the lipids of the inner membrane and to mitochondrial DNA.

Injuries among weightlifters and powerlifters: a systematic review.

Science.gov (United States)

Aasa, Ulrika; Svartholm, Ivar; Andersson, Fredrik; Berglund, Lars

2017-02-01

Olympic weightlifting and powerlifting are two sports that expose the body to great forces. Injury characteristics have not been systematically reviewed for these two growing sports. The purpose of this study was to systematically review the literature regarding various definitions of injuries used, injury localisation, the prevalence and incidence of injuries and the associated risk factors for injuries in weightlifting and powerlifting. Systematic review. Five databases, PubMed, MEDLINE, SPORTDiscus, Scopus and Web of Science, were searched between 9 March and 6 April 2015. Studies assessing injury incidence and prevalence in Olympic weightlifting and powerlifting were included. The Quality assessment tool for observational cohort and cross-sectional studies was used to assess methodological quality. 9 studies were included in the review. Injury was defined fairly consistently across studies. Most studies were of low methodological quality. The spine, shoulder and the knee were the most common injury localisations in both sports. The injury incidence in weightlifting was 2.4-3.3 injuries/1000 hours of training and 1.0-4.4 injuries/1000 hours of training in powerlifting. Only one retrospective study had analysed possible risk factors. The risk of injury in both sports were similar to other non-contact sports also requiring strength/power, but low compared to contact sports. The severity of injuries differed in the included studies. Since little has been studied regarding possible risk factors to injuries, further research is therefore warranted to explain why athletes get injured and how to prevent injuries. PROSPERO CRD42015014805. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Ring Avulsion Injuries: A Systematic Review.

Science.gov (United States)

Bamba, Ravinder; Malhotra, Gautam; Bueno, Reuben A; Thayer, Wesley P; Shack, R Bruce

2018-01-01

Ring avulsion injuries can range from soft tissue injury to complete amputation. Grading systems have been developed to guide treatment, but there is controversy with high-grade injuries. Traditionally, advanced ring injuries have been treated with completion amputation, but there is evidence that severe ring injuries can be salvaged. The purpose of this systematic review was to pool the current published data on ring injuries. A systematic review of the English literature published from 1980 to 2015 in PubMed and MEDLINE databases was conducted to identify patients who underwent treatment for ring avulsion injuries. Twenty studies of ring avulsion injuries met the inclusion criteria. There were a total of 572 patients reported with ring avulsion injuries. The Urbaniak class breakdown was class I (54 patients), class II (204 patients), and class III (314 patients). The average total arc of motion (TAM) for patients with a class I injury was 201.25 (n = 40). The average 2-point discrimination was 5.6 (n = 10). The average TAM for patients with a class II injury undergoing microsurgical revascularization was 187.0 (n = 114), and the average 2-point discrimination was 8.3 (n = 40). The average TAM for patients with a class III injury undergoing microsurgical revascularization was 168.2 (n = 170), and the average 2-point discrimination was 10.5 (n = 97). Ring avulsion injuries are commonly classified with the Urbaniak class system. Outcomes are superior for class I and II injuries, and there are select class III injuries that can be treated with replantation. Shared decision making with patients is imperative to determine whether replantation is appropriate.

S-52, a novel nootropic compound, protects against β-amyloid induced neuronal injury by attenuating mitochondrial dysfunction.

Science.gov (United States)

Gao, Xin; Zheng, Chun Yan; Qin, Guo Wei; Tang, Xi Can; Zhang, Hai Yan

2012-10-01

Accumulating evidence suggests that β-amyloid (Aβ)-induced oxidative DNA damage and mitochondrial dysfunction may initiate and contribute to the progression of Alzheimer's disease (AD). This study evaluated the neuroprotective effects of S-52, a novel nootropic compound, on Aβ-induced mitochondrial failure. In an established paradigm of moderate cellular injury induced by Aβ, S-52 was observed to attenuate the toxicity of Aβ to energy metabolism, mitochondrial membrane structure, and key enzymes in the electron transport chain and tricarboxylic acid cycle. In addition, S-52 also effectively inhibited reactive oxygen species accumulation dose dependently not only in Aβ-harmed cells but also in unharmed, normal cells. The role of S-52 as a scavenger of free radicals is involved in the antioxidative effect of this compound. The beneficial effects on mitochondria and oxidative stress extend the neuroprotective effects of S-52. The present study provides crucial information for better understanding the beneficial profiles of this compound and discovering novel potential drug candidates for AD therapy. Copyright © 2012 Wiley Periodicals, Inc.

Cardioprotection by modulation of mitochondrial respiration during ischemia–reperfusion: Role of apoptosis-inducing factor

Energy Technology Data Exchange (ETDEWEB)

Xu, Aijun [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030 (China); Szczepanek, Karol; Hu, Ying [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Lesnefsky, Edward J. [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298 (United States); McGuire Department of Veterans Affairs Medical Center, Richmond, VA 23249 (United States); Chen, Qun, E-mail: qchen8@vcu.edu [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States)

2013-06-14

Highlights: •Blockade of electron transport prevents the loss of AIF from mitochondria during IR. •Blockade of electron transport decreases caspase-independent cell death during IR. •Mitochondrial AIF content is down-regulated in Harlequin mice. •Blockade of electron transport protects Harlequin mouse hearts during IR. •Amobarbital protection is partially dependent on mitochondrial AIF content. -- Abstract: The transient, reversible blockade of electron transport (BET) during ischemia or at the onset of reperfusion protects mitochondria and decreases cardiac injury. Apoptosis inducing factor (AIF) is located within the mitochondrial intermembrane space. A release of AIF from mitochondria into cytosol and nucleus triggers caspase-independent cell death. We asked if BET prevents the loss of AIF from mitochondria as a mechanism of protection in the buffer perfused heart. BET during ischemia with amobarbital, a rapidly reversible inhibitor of mitochondrial complex I, attenuated a release of AIF from mitochondria into cytosol, in turn decreasing the formation of cleaved and activated PARP-1. These results suggest that BET-mediated protection may occur through prevention of the loss of AIF from mitochondria during ischemia–reperfusion. In order to further clarify the role of mitochondrial AIF in BET-mediated protection, Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, were used to test whether BET could still decrease cell injury in Hq mouse hearts during reperfusion. BET during ischemia protected Hq mouse hearts against ischemia–reperfusion injury and improved mitochondrial function in these hearts during reperfusion. Thus, cardiac injury can still be decreased in the presence of down-regulated mitochondrial AIF content. Taken together, BET during ischemia protects both hearts with normal mitochondrial AIF content and hearts with mitochondrial AIF deficiency. Although preservation of mitochondrial AIF content plays a key role in

Cardioprotection by modulation of mitochondrial respiration during ischemia–reperfusion: Role of apoptosis-inducing factor

International Nuclear Information System (INIS)

Xu, Aijun; Szczepanek, Karol; Hu, Ying; Lesnefsky, Edward J.; Chen, Qun

2013-01-01

Highlights: •Blockade of electron transport prevents the loss of AIF from mitochondria during IR. •Blockade of electron transport decreases caspase-independent cell death during IR. •Mitochondrial AIF content is down-regulated in Harlequin mice. •Blockade of electron transport protects Harlequin mouse hearts during IR. •Amobarbital protection is partially dependent on mitochondrial AIF content. -- Abstract: The transient, reversible blockade of electron transport (BET) during ischemia or at the onset of reperfusion protects mitochondria and decreases cardiac injury. Apoptosis inducing factor (AIF) is located within the mitochondrial intermembrane space. A release of AIF from mitochondria into cytosol and nucleus triggers caspase-independent cell death. We asked if BET prevents the loss of AIF from mitochondria as a mechanism of protection in the buffer perfused heart. BET during ischemia with amobarbital, a rapidly reversible inhibitor of mitochondrial complex I, attenuated a release of AIF from mitochondria into cytosol, in turn decreasing the formation of cleaved and activated PARP-1. These results suggest that BET-mediated protection may occur through prevention of the loss of AIF from mitochondria during ischemia–reperfusion. In order to further clarify the role of mitochondrial AIF in BET-mediated protection, Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, were used to test whether BET could still decrease cell injury in Hq mouse hearts during reperfusion. BET during ischemia protected Hq mouse hearts against ischemia–reperfusion injury and improved mitochondrial function in these hearts during reperfusion. Thus, cardiac injury can still be decreased in the presence of down-regulated mitochondrial AIF content. Taken together, BET during ischemia protects both hearts with normal mitochondrial AIF content and hearts with mitochondrial AIF deficiency. Although preservation of mitochondrial AIF content plays a key role in

Football injury: a literature review *

Science.gov (United States)

Kos, John J.

1979-01-01

A great deal of concern is recently being expressed relative to the playing of tackle football by adolescent Canadians. The purpose of this literature review is to try to summarize the important data from the available world literature. Very few Canadian statistics are available. Most of the data comes from United States experience. Tackle football injury is examined from various perspectives: 1. Equipment 2. Mechanisms of injury 3. Types of injury, with some emphasis on epiphyseal injury 4. Prevention 5. Comparison with other sports Although no “hard and fast” conclusion is drawn, the paper tends to show that: 1. Football is dangerous 2. Football is damaging to many body systems 3. Prevention of injury is difficult under present conditions 4. Alternate games, such as soccer and rugby seem to provide the same benefits with less catastrophic injuries

TSA protects H9c2 cells against thapsigargin-induced apoptosis related to endoplasmic reticulum stress-mediated mitochondrial injury.

Science.gov (United States)

Li, Zhiping; Liu, Yan; Dai, Xinlun; Zhou, Qiangqiang; Liu, Xueli; Li, Zeyu; Chen, Xia

2017-05-01

Endoplasmic reticulum stress (ERS) activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. Recently, TSA has shown protective effects on ERS and its mechanisms related to ER pathway has been previously characterized. However, whether TSA exerts its protective role via metabolic events remain largely undefined. Objectives : To explore the possible involvement of the metabolic changes during ERS and to better understand how TSA influence mitochondrial function to facilitate cellular adaptation. Results : TSA is an inhibitor of histone deacetylase which could significantly inhibit H9c2 cell apoptosis induced by Thapsigargin (TG). It also intervene the decrease of mitochondrial membrane potential. By immunofluorescence staining, we have shown that GRP78 was concentrated in the perinuclear region and co-localized with ER. However, treatments with TG and TSA could let it overlap with the mitochondrial marker MitoTracker. Cellular fractionation also confirmed the location of GRP78 in mitochondrion. TSA decreases ERS-induced cell apoptosis and mitochondrial injury may related to enhance the location of GRP78 in mitochondrion.

Mitochondrial Mechanisms of Neuronal Injury

National Research Council Canada - National Science Library

Reynolds, Ian

1999-01-01

.... In the acute form, this injury accounts for neural injury following stroke and head trauma, while in the chronic phenotype, it may account for degenerative diseases such as Parkinson's disease...

Brain injury with diabetes mellitus: evidence, mechanisms and treatment implications.

Science.gov (United States)

Hamed, Sherifa A

2017-04-01

Diabetes mellitus is a risk for brain injury. Brain injury is associated with acute and chronic hyperglycaemia, insulin resistance, hyperinsulinemia, diabetic ketoacidosis (DKA) and hypoglycaemic events in diabetic patients. Hyperglycemia is a cause of cognitive deterioration, low intelligent quotient, neurodegeneration, brain aging, brain atrophy and dementia. Areas covered: The current review highlights the experimental, clinical, neuroimaging and neuropathological evidence of brain injury induced by diabetes and its associated metabolic derangements. It also highlights the mechanisms of diabetes-induced brain injury. It seems that the pathogenesis of hyperglycemia-induced brain injury is complex and includes combination of vascular disease, oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis, reduction of neurotrophic factors, acetylcholinesterase (AChE) activation, neurotransmitters' changes, impairment of brain repair processes, impairment of brain glymphatic system, accumulation of amyloid β and tau phosphorylation and neurodegeneration. The potentials for prevention and treatment are also discussed. Expert commentary: We summarize the risks and the possible mechanisms of DM-induced brain injury and recommend strategies for neuroprotection and neurorestoration. Recently, a number of drugs and substances [in addition to insulin and its mimics] have shown promising potentials against diabetes-induced brain injury. These include: antioxidants, neuroinflammation inhibitors, anti-apoptotics, neurotrophic factors, AChE inhibitors, mitochondrial function modifiers and cell based therapies.

Mitochondrial damage-associated molecular patterns and vascular function†

Science.gov (United States)

Wenceslau, Camilla Ferreira; McCarthy, Cameron G.; Szasz, Theodora; Spitler, Kathryn; Goulopoulou, Styliani; Webb, R. Clinton

2014-01-01

Immune system activation occurs not only due to foreign stimuli, but also due to endogenous molecules. As such, endogenous molecules that are released into the circulation due to cell death and/or injury alarm the immune system that something has disturbed homeostasis and a response is needed. Collectively, these molecules are known as damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs (mtDAMPs) are potent immunological activators due to the bacterial ancestry of mitochondria. Mitochondrial DAMPs are recognized by specific pattern recognition receptors of the innate immune system, some of which are expressed in the cardiovascular system. Cell death leads to release of mtDAMPs that may induce vascular changes by mechanisms that are currently not well understood. This review will focus on recently published evidence linking mtDAMPs and immune system activation to vascular dysfunction and cardiovascular disease. PMID:24569027

C-Jun N-Terminal Kinase 2 Promotes Liver Injury via the Mitochondrial Permeability Transition after Hemorrhage and Resuscitation

Directory of Open Access Journals (Sweden)

Christoph Czerny

2012-01-01

Full Text Available Hemorrhagic shock leads to hepatic hypoperfusion and activation of mitogen-activated stress kinases (MAPK like c-Jun N-terminal kinase (JNK 1 and 2. Our aim was to determine whether mitochondrial dysfunction leading to hepatic necrosis and apoptosis after hemorrhage/resuscitation (H/R was dependent on JNK2. Under pentobarbital anesthesia, wildtype (WT and JNK2 deficient (KO mice were hemorrhaged to 30 mm Hg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer’s solution. Serum alanine aminotransferase (ALT, necrosis, apoptosis and oxidative stress were assessed 6 h after resuscitation. Mitochondrial polarization was assessed by intravital microscopy. After H/R, ALT in WT-mice increased from 130 U/L to 4800 U/L. In KO-mice, ALT after H/R was blunted to 1800 U/l (P<0.05. Necrosis, caspase-3 activity and ROS were all substantially decreased in KO compared to WT mice after H/R. After sham operation, intravital microscopy revealed punctate mitochondrial staining by rhodamine 123 (Rh123, indicating normal mitochondrial polarization. At 4 h after H/R, Rh123 staining became dim and diffuse in 58% of hepatocytes, indicating depolarization and onset of the mitochondrial permeability transition (MPT. By contrast, KO mice displayed less depolarization after H/R (23%, P<0.05. In conclusion, JNK2 contributes to MPT-mediated liver injury after H/R.

Ursolic Acid-enriched herba cynomorii extract induces mitochondrial uncoupling and glutathione redox cycling through mitochondrial reactive oxygen species generation: protection against menadione cytotoxicity in h9c2 cells.

Science.gov (United States)

Chen, Jihang; Wong, Hoi Shan; Ko, Kam Ming

2014-01-27

Herba Cynomorii (Cynomorium songaricum Rupr., Cynomoriaceae) is one of the most commonly used 'Yang-invigorating' tonic herbs in Traditional Chinese Medicine (TCM). An earlier study in our laboratory has demonstrated that HCY2, an ursolic acid-enriched fraction derived from Herba Cynomorii, increased mitochondrial ATP generation capacity (ATP-GC) and induced mitochondrial uncoupling as well as a cellular glutathione response, thereby protecting against oxidant injury in H9c2 cells. In this study, we demonstrated that pre-incubation of H9c2 cells with HCY2 increased mitochondrial reactive oxygen species (ROS) generation in these cells, which is likely an event secondary to the stimulation of the mitochondrial electron transport chain. The suppression of mitochondrial ROS by the antioxidant dimethylthiourea abrogated the HCY2-induced enhancement of mitochondrial uncoupling and glutathione reductase (GR)-mediated glutathione redox cycling, and also protected against menadione-induced cytotoxicity. Studies using specific inhibitors of uncoupling protein and GR suggested that the HCY2-induced mitochondrial uncoupling and glutathione redox cycling play a determining role in the cytoprotection against menadione-induced oxidant injury in H9c2 cells. Experimental evidence obtained thus far supports the causal role of HCY2-induced mitochondrial ROS production in eliciting mitochondrial uncoupling and glutathione antioxidant responses, which offer cytoprotection against oxidant injury in H9c2 cells.

Oxidative muscular injury and its relevance to hyperthyroidism.

Science.gov (United States)

Asayama, K; Kato, K

1990-01-01

In experimental hyperthyroidism, acceleration of lipid peroxidation occurs in heart and slow-oxidative muscles, suggesting the contribution of reactive oxygen species to the muscular injury caused by thyroid hormones. This article reviews various models of oxidative muscular injury and considers the relevance of the accompanying metabolic derangements to thyrotoxic myopathy and cardiomyopathy, which are the major complications of hyperthyroidism. The muscular injury models in which reactive oxygen species are supposed to play a role are ischemia/reperfusion syndrome, exercise-induced myopathy, heart and skeletal muscle diseases related to the nutritional deficiency of selenium and vitamin E and related disorders, and genetic muscular dystrophies. These models provide evidence that mitochondrial function and the glutathione-dependent antioxidant system are important for the maintenance of the structural and functional integrity of muscular tissues. Thyroid hormones have a profound effect on mitochondrial oxidative activity, synthesis and degradation of proteins and vitamin E, the sensitivity of the tissues to catecholamine, the differentiation of muscle fibers, and the levels of antioxidant enzymes. The large volume of circumstantial evidence presented here indicates that hyperthyroid muscular tissues undergo several biochemical changes that predispose them to free radical-mediated injury.

The impact of partial manganese superoxide dismutase (SOD2)-deficiency on mitochondrial oxidant stress, DNA fragmentation and liver injury during acetaminophen hepatotoxicity

International Nuclear Information System (INIS)

Ramachandran, Anup; Lebofsky, Margitta; Weinman, Steven A.; Jaeschke, Hartmut

2011-01-01

Acetaminophen (APAP) hepatotoxicity is the most frequent cause of acute liver failure in many countries. The mechanism of cell death is initiated by formation of a reactive metabolite that binds to mitochondrial proteins and promotes mitochondrial dysfunction and oxidant stress. Manganese superoxide dismutase (SOD2) is a critical defense enzyme located in the mitochondrial matrix. The objective of this investigation was to evaluate the functional consequences of partial SOD2-deficiency (SOD2+/-) on intracellular signaling mechanisms of necrotic cell death after APAP overdose. Treatment of C57Bl/6J wild type animals with 200 mg/kg APAP resulted in liver injury as indicated by elevated plasma alanine aminotransferase activities (2870 ± 180 U/L) and centrilobular necrosis at 6 h. In addition, increased tissue glutathione disulfide (GSSG) levels and GSSG-to-GSH ratios, delayed mitochondrial GSH recovery, and increased mitochondrial protein carbonyls and nitrotyrosine protein adducts indicated mitochondrial oxidant stress. In addition, nuclear DNA fragmentation (TUNEL assay) correlated with translocation of Bax to the mitochondria and release of apoptosis-inducing factor (AIF). Furthermore, activation of c-jun-N-terminal kinase (JNK) was documented by the mitochondrial translocation of phospho-JNK. SOD2+/- mice showed 4-fold higher ALT activities and necrosis, an enhancement of all parameters of the mitochondrial oxidant stress, more AIF release and more extensive DNA fragmentation and more prolonged JNK activation. Conclusions: the impaired defense against mitochondrial superoxide formation in SOD2+/- mice prolongs JNK activation after APAP overdose and consequently further enhances the mitochondrial oxidant stress leading to exaggerated mitochondrial dysfunction, release of intermembrane proteins with nuclear DNA fragmentation and more necrosis.

Moderate ethanol administration accentuates cardiomyocyte contractile dysfunction and mitochondrial injury in high fat diet-induced obesity.

Science.gov (United States)

Yuan, Fang; Lei, Yonghong; Wang, Qiurong; Esberg, Lucy B; Huang, Zaixing; Scott, Glenda I; Li, Xue; Ren, Jun

2015-03-18

Light to moderate drinking confers cardioprotection although it remains unclear with regards to the role of moderate drinking on cardiac function in obesity. This study was designed to examine the impact of moderate ethanol intake on myocardial function in high fat diet intake-induced obesity and the mechanism(s) involved with a focus on mitochondrial integrity. C57BL/6 mice were fed low or high fat diet for 16 weeks prior to ethanol challenge (1g/kg/d for 3 days). Cardiac contractile function, intracellular Ca(2+) homeostasis, myocardial histology, and mitochondrial integrity [aconitase activity and the mitochondrial proteins SOD1, UCP-2 and PPARγ coactivator 1α (PGC-1α)] were assessed 24h after the final ethanol challenge. Fat diet intake compromised cardiomyocyte contractile and intracellular Ca(2+) properties (depressed peak shortening and maximal velocities of shortening/relengthening, prolonged duration of relengthening, dampened intracellular Ca(2+) rise and clearance without affecting duration of shortening). Although moderate ethanol challenge failed to alter cardiomyocyte mechanical property under low fat diet intake, it accentuated high fat diet intake-induced changes in cardiomyocyte contractile function and intracellular Ca(2+) handling. Moderate ethanol challenge failed to affect fat diet intake-induced cardiac hypertrophy as evidenced by H&E staining. High fat diet intake reduced myocardial aconitase activity, downregulated levels of mitochondrial protein UCP-2, PGC-1α, SOD1 and interrupted intracellular Ca(2+) regulatory proteins, the effect of which was augmented by moderate ethanol challenge. Neither high fat diet intake nor moderate ethanol challenge affected protein or mRNA levels as well as phosphorylation of Akt and GSK3β in mouse hearts. Taken together, our data revealed that moderate ethanol challenge accentuated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies as well as mitochondrial injury. Copyright �

Mitochondrial Dysfunction and β-Cell Failure in Type 2 Diabetes Mellitus

Directory of Open Access Journals (Sweden)

Zhongmin Alex Ma

2012-01-01

Full Text Available Type 2 diabetes mellitus (T2DM is the most common human endocrine disease and is characterized by peripheral insulin resistance and pancreatic islet β-cell failure. Accumulating evidence indicates that mitochondrial dysfunction is a central contributor to β-cell failure in the evolution of T2DM. As reviewed elsewhere, reactive oxygen species (ROS produced by β-cell mitochondria as a result of metabolic stress activate several stress-response pathways. This paper focuses on mechanisms whereby ROS affect mitochondrial structure and function and lead to β-cell failure. ROS activate UCP2, which results in proton leak across the mitochondrial inner membrane, and this leads to reduced β-cell ATP synthesis and content, which is a critical parameter in regulating glucose-stimulated insulin secretion. In addition, ROS oxidize polyunsaturated fatty acids in mitochondrial cardiolipin and other phospholipids, and this impairs membrane integrity and leads to cytochrome c release into cytosol and apoptosis. Group VIA phospholipase A2 (iPLA2β appears to be a component of a mechanism for repairing mitochondrial phospholipids that contain oxidized fatty acid substituents, and genetic or acquired iPLA2β-deficiency increases β-cell mitochondrial susceptibility to injury from ROS and predisposes to developing T2DM. Interventions that attenuate ROS effects on β-cell mitochondrial phospholipids might prevent or retard development of T2DM.

Hydrogen sulfide preconditioning protects rat liver against ischemia/reperfusion injury by activating Akt-GSK-3β signaling and inhibiting mitochondrial permeability transition.

Directory of Open Access Journals (Sweden)

Qingqing Zhang

Full Text Available Hydrogen sulfide (H2S is the third most common endogenously produced gaseous signaling molecule, but its impact on hepatic ischemia/reperfusion (I/R injury, especially on mitochondrial function, remains unclear. In this study, rats were randomized into Sham, I/R, ischemia preconditioning (IPC or sodium hydrosulfide (NaHS, an H2S donor preconditioning groups. To establish a model of segmental (70% warm hepatic ischemia, the hepatic artery, left portal vein and median liver lobes were occluded for 60 min and then unclamped to allow reperfusion. Preconditioning with 12.5, 25 or 50 μmol/kg NaHS prior to the I/R insult significantly increased serum H2S levels, and, similar to IPC, NaHS preconditioning decreased alanine aminotransferase (ALT and aspartate aminotransferase (AST levels in the plasma and prevented hepatocytes from undergoing I/R-induced necrosis. Moreover, a sub-toxic dose of NaHS (25 μmol/kg did not disrupt the systemic hemodynamics but dramatically inhibited mitochondrial permeability transition pore (MPTP opening and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that NaHS preconditioning markedly increased the expression of phosphorylated protein kinase B (p-Akt, phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β and B-cell lymphoma-2 (Bcl-2 and decreased the release of mitochondrial cytochrome c and cleaved caspase-3/9 levels. Therefore, NaHS administration prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through the inhibition of MPTP opening and the activation of Akt-GSK-3β signaling. Furthermore, this study provides experimental evidence for the clinical use of H2S to reduce liver damage after perioperative I/R injury.

Evolving colon injury management: a review.

Science.gov (United States)

Greer, Lauren T; Gillern, Suzanne M; Vertrees, Amy E

2013-02-01

The colon is the second most commonly injured intra-abdominal organ in penetrating trauma. Management of traumatic colon injuries has evolved significantly over the past 200 years. Traumatic colon injuries can have a wide spectrum of severity, presentation, and management options. There is strong evidence that most non-destructive colon injuries can be successfully managed with primary repair or primary anastomosis. The management of destructive colon injuries remains controversial with most favoring resection with primary anastomosis and others favor colonic diversion in specific circumstances. The historical management of traumatic colon injuries, common mechanisms of injury, demographics, presentation, assessment, diagnosis, management, and complications of traumatic colon injuries both in civilian and military practice are reviewed. The damage control revolution has added another layer of complexity to management with continued controversy.

Redox imbalance and mitochondrial abnormalities in the diabetic lung.

Science.gov (United States)

Wu, Jinzi; Jin, Zhen; Yan, Liang-Jun

2017-04-01

Although the lung is one of the least studied organs in diabetes, increasing evidence indicates that it is an inevitable target of diabetic complications. Nevertheless, the underlying biochemical mechanisms of lung injury in diabetes remain largely unexplored. Given that redox imbalance, oxidative stress, and mitochondrial dysfunction have been implicated in diabetic tissue injury, we set out to investigate mechanisms of lung injury in diabetes. The objective of this study was to evaluate NADH/NAD + redox status, oxidative stress, and mitochondrial abnormalities in the diabetic lung. Using STZ induced diabetes in rat as a model, we measured redox-imbalance related parameters including aldose reductase activity, level of poly ADP ribose polymerase (PAPR-1), NAD + content, NADPH content, reduced form of glutathione (GSH), and glucose 6-phophate dehydrogenase (G6PD) activity. For assessment of mitochondrial abnormalities in the diabetic lung, we measured the activities of mitochondrial electron transport chain complexes I to IV and complex V as well as dihydrolipoamide dehydrogenase (DLDH) content and activity. We also measured the protein content of NAD + dependent enzymes such as sirtuin3 (sirt3) and NAD(P)H: quinone oxidoreductase 1 (NQO1). Our results demonstrate that NADH/NAD + redox imbalance occurs in the diabetic lung. This redox imbalance upregulates the activities of complexes I to IV, but not complex V; and this upregulation is likely the source of increased mitochondrial ROS production, oxidative stress, and cell death in the diabetic lung. These results, together with the findings that the protein contents of DLDH, sirt3, and NQO1 all are decreased in the diabetic lung, demonstrate that redox imbalance, mitochondrial abnormality, and oxidative stress contribute to lung injury in diabetes. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Self-injury and externalizing pathology: a systematic literature review

OpenAIRE

Meszaros, Gergely; Horvath, Lili Olga; Balazs, Judit

2017-01-01

Background During the last decade there is a growing scientific interest in nonsuicidal self-injury (NSSI). The aim of the current paper was to review systematically the literature with a special focus on the associations between self-injurious behaviours and externalizing psychopathology. An additional aim was to review terminology and measurements of self-injurious behaviour and the connection between self-injurious behaviours and suicide in the included publications. Methods A systematic l...

Review of sport-induced groin injuries.

Science.gov (United States)

Sedaghati, Parisa; Alizadeh, Mohammad-Hossein; Shirzad, Elham; Ardjmand, Abolfazl

2013-12-01

Groin injuries are among the most common injuries co-existing with sports. The aim of this review was to outline the epidemiology and identify risk factors, as well as examine preventative and interventional measures for reducing the occurrence of this form of injury among athletes. An electronic, systematic search for relevant keywords, either separately or in combination was sought in the academic scientific databases. Groin injuries, acute or chronic, consist of a high percentage of injuries that manifest with pain. Despite the specific tendency for injury among some sports, such injuries make up 2-5% of sport-induced injuries. There are few available reports on lower limb injuries, especially groin injuries, in Iran. Numerous factors predispose to groin injuries. A lengthy list of preventive/ treatment measures, from preliminary to sophisticated, have been proposed. Although using a programmed strategy designed to decrease the risk of groin injuries by taking a strategic approach to exercise may alleviate complications, in some cases the chronic nature of the injury may threaten the professional life of the athlete. More research is required to plan suitable programs for reducing the risk of this type of injury in athletes.

Epidemiological Review of Injuries in Rugby Union

Directory of Open Access Journals (Sweden)

Jean-François Kaux

2015-01-01

Full Text Available Rugby is a sport that is growing in popularity. A contact sport par excellence, it causes a significant number of injuries. In Rugby Union, there are 30 to 91 injuries per 1000 match hours. This epidemiological review of injuries incurred by rugby players mentions the position and type of injuries, the causes, time during the match and season in which they occur and the players’ positions as well as the length of players’ absences following the injury.

Alcohol Withdrawal and Brain Injuries: Beyond Classical Mechanisms

Directory of Open Access Journals (Sweden)

Marianna E. Jung

2010-07-01

Full Text Available Unmanaged sudden withdrawal from the excessive consumption of alcohol (ethanol adversely alters neuronal integrity in vulnerable brain regions such as the cerebellum, hippocampus, or cortex. In addition to well known hyperexcitatory neurotransmissions, ethanol withdrawal (EW provokes the intense generation of reactive oxygen species (ROS and the activation of stress-responding protein kinases, which are the focus of this review article. EW also inflicts mitochondrial membranes/membrane potential, perturbs redox balance, and suppresses mitochondrial enzymes, all of which impair a fundamental function of mitochondria. Moreover, EW acts as an age-provoking stressor. The vulnerable age to EW stress is not necessarily the oldest age and varies depending upon the target molecule of EW. A major female sex steroid, 17β-estradiol (E2, interferes with the EW-induced alteration of oxidative signaling pathways and thereby protects neurons, mitochondria, and behaviors. The current review attempts to provide integrated information at the levels of oxidative signaling mechanisms by which EW provokes brain injuries and E2 protects against it. Unmanaged sudden withdrawal from the excessive consumption of alcohol (ethanol adversely alters neuronal integrity in vulnerable brain regions such as the cerebellum, hippocampus, or cortex. In addition to well known hyperexcitatory neurotransmissions, ethanol withdrawal (EW provokes the intense generation of reactive oxygen species (ROS and the activation of stress-responding protein kinases, which are the focus of this review article. EW also inflicts mitochondrial membranes/membrane potential, perturbs redox balance, and suppresses mitochondrial enzymes, all of which impair a fundamental function of mitochondria. Moreover, EW acts as an age-provoking stressor. The vulnerable age to EW stress is not necessarily the oldest age and varies depending upon the target molecule of EW. A major female sex steroid, 17�

Chymase mediates injury and mitochondrial damage in cardiomyocytes during acute ischemia/reperfusion in the dog.

Science.gov (United States)

Zheng, Junying; Wei, Chih-Chang; Hase, Naoki; Shi, Ke; Killingsworth, Cheryl R; Litovsky, Silvio H; Powell, Pamela C; Kobayashi, Tsunefumi; Ferrario, Carlos M; Rab, Andras; Aban, Inmaculada; Collawn, James F; Dell'Italia, Louis J

2014-01-01

Cardiac ischemia and reperfusion (I/R) injury occurs because the acute increase in oxidative/inflammatory stress during reperfusion culminates in the death of cardiomyocytes. Currently, there is no drug utilized clinically that attenuates I/R injury in patients. Previous studies have demonstrated degranulation of mast cell contents into the interstitium after I/R. Using a dog model of I/R, we tested the role of chymase, a mast cell protease, in cardiomyocyte injury using a specific oral chymase inhibitor (CI). 15 adult mongrel dogs had left anterior descending artery occlusion for 60 min and reperfusion for 100 minutes. 9 dogs received vehicle and 6 were pretreated with a specific CI. In vivo cardiac microdialysis demonstrated a 3-fold increase in interstitial fluid chymase activity in I/R region that was significantly decreased by CI. CI pretreatment significantly attenuated loss of laminin, focal adhesion complex disruption, and release of troponin I into the circulation. Microarray analysis identified an I/R induced 17-fold increase in nuclear receptor subfamily 4A1 (NR4A1) and significantly decreased by CI. NR4A1 normally resides in the nucleus but can induce cell death on migration to the cytoplasm. I/R caused significant increase in NR4A1 protein expression and cytoplasmic translocation, and mitochondrial degradation, which were decreased by CI. Immunohistochemistry also revealed a high concentration of chymase within cardiomyocytes after I/R. In vitro, chymase added to culture HL-1 cardiomyocytes entered the cytoplasm and nucleus in a dynamin-dependent fashion, and promoted cytoplasmic translocation of NR4A1 protein. shRNA knockdown of NR4A1 on pre-treatment of HL-1 cells with CI significantly decreased chymase-induced cell death and mitochondrial damage. These results suggest that the beneficial effects of an orally active CI during I/R are mediated in the cardiac interstitium as well as within the cardiomyocyte due to a heretofore-unrecognized chymase

Chymase mediates injury and mitochondrial damage in cardiomyocytes during acute ischemia/reperfusion in the dog.

Directory of Open Access Journals (Sweden)

Junying Zheng

Full Text Available Cardiac ischemia and reperfusion (I/R injury occurs because the acute increase in oxidative/inflammatory stress during reperfusion culminates in the death of cardiomyocytes. Currently, there is no drug utilized clinically that attenuates I/R injury in patients. Previous studies have demonstrated degranulation of mast cell contents into the interstitium after I/R. Using a dog model of I/R, we tested the role of chymase, a mast cell protease, in cardiomyocyte injury using a specific oral chymase inhibitor (CI. 15 adult mongrel dogs had left anterior descending artery occlusion for 60 min and reperfusion for 100 minutes. 9 dogs received vehicle and 6 were pretreated with a specific CI. In vivo cardiac microdialysis demonstrated a 3-fold increase in interstitial fluid chymase activity in I/R region that was significantly decreased by CI. CI pretreatment significantly attenuated loss of laminin, focal adhesion complex disruption, and release of troponin I into the circulation. Microarray analysis identified an I/R induced 17-fold increase in nuclear receptor subfamily 4A1 (NR4A1 and significantly decreased by CI. NR4A1 normally resides in the nucleus but can induce cell death on migration to the cytoplasm. I/R caused significant increase in NR4A1 protein expression and cytoplasmic translocation, and mitochondrial degradation, which were decreased by CI. Immunohistochemistry also revealed a high concentration of chymase within cardiomyocytes after I/R. In vitro, chymase added to culture HL-1 cardiomyocytes entered the cytoplasm and nucleus in a dynamin-dependent fashion, and promoted cytoplasmic translocation of NR4A1 protein. shRNA knockdown of NR4A1 on pre-treatment of HL-1 cells with CI significantly decreased chymase-induced cell death and mitochondrial damage. These results suggest that the beneficial effects of an orally active CI during I/R are mediated in the cardiac interstitium as well as within the cardiomyocyte due to a heretofore

Mpv17 in mitochondria protects podocytes against mitochondrial dysfunction and apoptosis in vivo and in vitro.

Science.gov (United States)

Casalena, Gabriela; Krick, Stefanie; Daehn, Ilse; Yu, Liping; Ju, Wenjun; Shi, Shaolin; Tsai, Su-yi; D'Agati, Vivette; Lindenmeyer, Maja; Cohen, Clemens D; Schlondorff, Detlef; Bottinger, Erwin P

2014-06-01

Mitochondrial dysfunction is increasingly recognized as contributing to glomerular diseases, including those secondary to mitochondrial DNA (mtDNA) mutations and deletions. Mitochondria maintain cellular redox and energy homeostasis and are a major source of intracellular reactive oxygen species (ROS) production. Mitochondrial ROS accumulation may contribute to stress-induced mitochondrial dysfunction and apoptosis and thereby to glomerulosclerosis. In mice, deletion of the gene encoding Mpv17 is associated with glomerulosclerosis, but the underlying mechanism remains poorly defined. Here we report that Mpv17 localizes to mitochondria of podocytes and its expression is reduced in several glomerular injury models and in human focal segmental glomerulosclerosis (FSGS) but not in minimal change disease. Using models of mild or severe nephrotoxic serum nephritis (NTSN) in Mpv17(+/+) wild-type (WT) and Mpv17(-/-) knockout mice, we found that Mpv17 deficiency resulted in increased proteinuria (mild NTSN) and renal insufficiency (severe NTSN) compared with WT. These lesions were associated with increased mitochondrial ROS generation and mitochondrial injury such as oxidative DNA damage. In vitro, podocytes with loss of Mpv17 function were characterized by increased susceptibility to apoptosis and ROS injury including decreased mitochondrial function, loss of mtDNA content, and change in mitochondrial configuration. In summary, the inner mitochondrial membrane protein Mpv17 in podocytes is essential for the maintenance of mitochondrial homeostasis and protects podocytes against oxidative stress-induced injury both in vitro and in vivo. Copyright © 2014 the American Physiological Society.

Non-accidental injury: a review of the radiology

International Nuclear Information System (INIS)

Carty, H.

1997-01-01

There have been many descriptions of the radiological features of non-accidental injury since John Caffey introduced the concept of inflicted injury and initially described some of the patterns of injury. Since then, our understanding of the radiologically detectable injuries has increased. This article provides a review of our current understanding of the lesions. (orig.)

Mitochondrial myopathies.

Science.gov (United States)

DiMauro, Salvatore

2006-11-01

Our understanding of mitochondrial diseases (defined restrictively as defects of the mitochondrial respiratory chain) is expanding rapidly. In this review, I will give the latest information on disorders affecting predominantly or exclusively skeletal muscle. The most recently described mitochondrial myopathies are due to defects in nuclear DNA, including coenzyme Q10 deficiency and mutations in genes controlling mitochondrial DNA abundance and structure, such as POLG, TK2, and MPV17. Barth syndrome, an X-linked recessive mitochondrial myopathy/cardiopathy, is associated with decreased amount and altered structure of cardiolipin, the main phospholipid of the inner mitochondrial membrane, but a secondary impairment of respiratory chain function is plausible. The role of mutations in protein-coding genes of mitochondrial DNA in causing isolated myopathies has been confirmed. Mutations in tRNA genes of mitochondrial DNA can also cause predominantly myopathic syndromes and--contrary to conventional wisdom--these mutations can be homoplasmic. Defects in the mitochondrial respiratory chain impair energy production and almost invariably involve skeletal muscle, causing exercise intolerance, cramps, recurrent myoglobinuria, or fixed weakness, which often affects extraocular muscles and results in droopy eyelids (ptosis) and progressive external ophthalmoplegia.

Mitochondrial Dysfunction in Metabolic Syndrome and Asthma

Science.gov (United States)

Mabalirajan, Ulaganathan; Ghosh, Balaram

2013-01-01

Though severe or refractory asthma merely affects less than 10% of asthma population, it consumes significant health resources and contributes significant morbidity and mortality. Severe asthma does not fell in the routine definition of asthma and requires alternative treatment strategies. It has been observed that asthma severity increases with higher body mass index. The obese-asthmatics, in general, have the features of metabolic syndrome and are progressively causing a significant burden for both developed and developing countries thanks to the westernization of the world. As most of the features of metabolic syndrome seem to be originated from central obesity, the underlying mechanisms for metabolic syndrome could help us to understand the pathobiology of obese-asthma condition. While mitochondrial dysfunction is the common factor for most of the risk factors of metabolic syndrome, such as central obesity, dyslipidemia, hypertension, insulin resistance, and type 2 diabetes, the involvement of mitochondria in obese-asthma pathogenesis seems to be important as mitochondrial dysfunction has recently been shown to be involved in airway epithelial injury and asthma pathogenesis. This review discusses current understanding of the overlapping features between metabolic syndrome and asthma in relation to mitochondrial structural and functional alterations with an aim to uncover mechanisms for obese-asthma. PMID:23840225

Molecular Mechanisms of Neonatal Brain Injury

Directory of Open Access Journals (Sweden)

Claire Thornton

2012-01-01

Full Text Available Fetal/neonatal brain injury is an important cause of neurological disability. Hypoxia-ischemia and excitotoxicity are considered important insults, and, in spite of their acute nature, brain injury develops over a protracted time period during the primary, secondary, and tertiary phases. The concept that most of the injury develops with a delay after the insult makes it possible to provide effective neuroprotective treatment after the insult. Indeed, hypothermia applied within 6 hours after birth in neonatal encephalopathy reduces neurological disability in clinical trials. In order to develop the next generation of treatment, we need to know more about the pathophysiological mechanism during the secondary and tertiary phases of injury. We review some of the critical molecular events related to mitochondrial dysfunction and apoptosis during the secondary phase and report some recent evidence that intervention may be feasible also days-weeks after the insult.

Dynamin-Related Protein 1 Inhibitors Protect against Ischemic Toxicity through Attenuating Mitochondrial Ca2+ Uptake from Endoplasmic Reticulum Store in PC12 Cells

Directory of Open Access Journals (Sweden)

Ye Tian

2014-02-01

Full Text Available Intracellular calcium homeostasis disorder and mitochondrial dysfunction are involved in many acute and chronic brain diseases, including ischemic brain injury. An imbalance in mitochondrial fission and fusion is one of the most important structural abnormalities found in a large number of mitochondrial dysfunction related diseases. Here, we investigated the effects of mitochondrial division inhibitor A (mdivi A and mdivi B, two small molecule inhibitors of mitochondrial fission protein dunamin-related protein 1 (Drp-1, in neuronal injury induced by oxygen-glucose deprivation (OGD in PC12 cells. We found that mdivi A and mdivi B inhibited OGD-induced neuronal injury through attenuating apoptotic cell death. These two inhibitors also preserved mitochondrial function, as evidenced by reduced reactive oxygen species (ROS generation and cytochrome c release, as well as prevented loss of mitochondrial membrane potential (MMP. Moreover, mdivi A and mdivi B significantly suppressed mitochondrial Ca2+ uptake, but had no effect on cytoplasmic Ca2+ after OGD injury. The results of calcium imaging and immunofluorescence staining showed that Drp-1 inhibitors attenuated endoplasmic reticulum (ER Ca2+ release and prevented ER morphological changes induced by OGD. These results demonstrate that Drp-1 inhibitors protect against ischemic neuronal injury through inhibiting mitochondrial Ca2+ uptake from the ER store and attenuating mitochondrial dysfunction.

Skateboarding injuries: An updated review.

Science.gov (United States)

Shuman, Kristin M; Meyers, Michael C

2015-07-01

This in-depth literature review shows that skateboarding has experienced intermittent periods of popularity, with an estimated 6-15 million skateboarders in the US currently involved at all levels of recreational play and competition. Head trauma accounts for ∼ 3.5-13.1% of all skateboarding injuries. Injury occurs most often to the upper extremity (55-63%), whereas thoracoabdominal and spine injuries account for 1.5-2.9% of all trauma and lower extremity injuries occur 17-26% of the time. Few fatal injuries (1.1%) have been reported, oftentimes resulting from traumatic head injuries incurred from collisions with motor vehicles. Although skateparks may be perceived as a safer alternative to street skateboarding, injuries still occur when the skateboarder collides with an object or falls from the board. Factors leading to trauma include fatigue and overuse, age and skill level, inadequate medical care, environmental conditions, equipment concerns, lack of fitness and training, and the detrimental behavior of the competitor. Although not all skateboarding injuries are avoidable, numerous opportunities exist to instill safety involving education, instruction, and supervision and the proper use of protective gear to reduce predisposition to trauma. Future research recommendations include a more standardized data collection system, as well as an increased focus on kinetic analysis of the sport. Legislation involving helmet laws and the increased investment in a safer environment for the skateboarder may also assist in reducing injury in this sport.

Pre-ischemic mitochondrial substrate constraint by inhibition of malate-aspartate shuttle preserves mitochondrial function after ischemia-reperfusion

DEFF Research Database (Denmark)

Jespersen, Nichlas Riise; Yokota, Takashi; Støttrup, Nicolaj Brejnholt

2017-01-01

KEY POINTS: Pre-ischaemic administration of aminooxiacetate (AOA), an inhibitor of the malate-aspartate shuttle (MAS), provides cardioprotection against ischaemia-reperfusion injury. The underlying mechanism remains unknown. We examined whether transient inhibition of the MAS during ischaemia......, but not IPC, reduced the myocardial interstitial concentration of tricarboxylic acid cycle intermediates at the onset of reperfusion. The results obtained in the present study demonstrate that metabolic regulation by inhibition of the MAS at the onset of reperfusion may be beneficial for the preservation...... of mitochondrial function during late reperfusion in an IR-injured heart. ABSTRACT: Mitochondrial dysfunction plays a central role in ischaemia-reperfusion (IR) injury. Pre-ischaemic administration of aminooxyacetate (AOA), an inhibitor of the malate-aspartate shuttle (MAS), provides cardioprotection against IR...

Succinate-induced neuronal mitochondrial fission and hexokinase II malfunction in ischemic stroke: Therapeutical effects of kaempferol.

Science.gov (United States)

Wu, Bin; Luo, Hong; Zhou, Xu; Cheng, Cai-Yi; Lin, Lin; Liu, Bao-Lin; Liu, Kang; Li, Ping; Yang, Hua

2017-09-01

Mitochondrial dysfunction is known as one of causative factors in ischemic stroke, leading to neuronal cell death. The present work was undertaken to investigate whether succinate induces neuron apoptosis by regulating mitochondrial morphology and function. In neurons, oxygen-glucose deprivation induced succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation, leading to mitochondrial fission. Kaempferol inhibited mitochondrial fission and maintained mitochondrial HK-II through activation of Akt, and thereby protected neurons from succinate-mediated ischemi injury. Knockdown of Akt2 with siRNA diminished the effect of kaempferol, indicating that kaempferol suppressed dynamin-related protein 1 (Drp1) activation and promoted HK-II mitochondrial binding dependently on Akt. Moreover, we demonstrated that kaempferol potentiated autophagy during oxygen and glucose deprivation, contributing to protecting neuron survival against succinate insult. In vivo, oral administration of kaempferol in mice attenuated the infract volume after ischemic and reperfusion (I/R) injury and reproduced the similar mitochondrial protective effect in the brain infract area. This study indicates that succinate accumulation plays a pivotal role in I/R injury-induced neuronal mitochondrial dysfunction, and suggests that modulation of Drp1 phosphorylation might be potential therapeutic strategy to protect neuron mitochondrial integrity and treat ischemic stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-injury and externalizing pathology: a systematic literature review.

Science.gov (United States)

Meszaros, Gergely; Horvath, Lili Olga; Balazs, Judit

2017-05-03

During the last decade there is a growing scientific interest in nonsuicidal self-injury (NSSI). The aim of the current paper was to review systematically the literature with a special focus on the associations between self-injurious behaviours and externalizing psychopathology. An additional aim was to review terminology and measurements of self-injurious behaviour and the connection between self-injurious behaviours and suicide in the included publications. A systematic literature search was conducted on 31st December 2016 in five databases (PubMed, OVID Medline, OVID PsycINFO, Scopus, Web of Science) with two categories of search terms (1. nonsuicidal self-injury, non-suicidal self-injury, NSSI, self-injurious behaviour, SIB, deliberate self-harm, DSH, self-injury; 2. externalizing disorder, attention deficit hyperactivity disorder, ADHD, conduct disorder, CD, oppositional defiant disorder, OD, ODD). Finally 35 papers were included. Eleven different terms were found for describing self-injurious behaviours and 20 methods for measuring it. NSSI has the clearest definition. All the examined externalizing psychopathologies had strong associations with self-injurious behaviours according to: higher prevalence rates in externalizing groups than in control groups, higher externalizing scores on the externalizing scales of questionnaires, higher symptom severity in self-injurious groups. Eight studies investigated the relationship between suicide and self-injurious behaviours and found high overlap between the two phenomena and similar risk factors. Based on the current findings the association between externalizing psychopathology and self-injurious behaviours has been proven by the scientific literature. Similarly to other reviews on self-injurious behaviours the confusion in terminology and methodology was noticed. NSSI is suggested for use as a distinct term. Further studies should investigate the role of comorbid conditions in NSSI, especially when internalizing

Mitochondrial autophagy involving renal injury and aging is modulated by caloric intake in aged rat kidneys.

Science.gov (United States)

Cui, Jing; Shi, Suozhu; Sun, Xuefeng; Cai, Guangyan; Cui, Shaoyuan; Hong, Quan; Chen, Xiangmei; Bai, Xue-Yuan

2013-01-01

A high-calorie (HC) diet induces renal injury and promotes aging, and calorie restriction (CR) may ameliorate these responses. However, the effects of long-term HC and CR on renal damage and aging have been not fully determined. Autophagy plays a crucial role in removing protein aggregates and damaged organelles to maintain intracellular homeostasis and function. The role of autophagy in HC-induced renal damage is unknown. We evaluated the expression of LC3/Atg8 as a marker of the autophagosome; p62/SQSTM1; polyubiquitin aggregates as markers of autophagy flux; Ambra1, PINK1, Parkin and Bnip3 as markers of mitophagy; 8-hydroxydeoxyguanosine (8-OHdG) as a marker of DNA oxidative damage; and p16 as a marker of organ aging by western blot and immunohistochemical staining in the kidneys of 24-month-old Fischer 344 rats. We also observed mitochondrial structure and autolysosomes by transmission electron microscopy. Expression of the autophagosome formation marker LC3/Atg8 and markers of mitochondrial autophagy (mitophagy) were markedly decreased in the kidneys of the HC group, and markedly increased in CR kidneys. p62/SQSTM1 and polyubiquitin aggregates increased in HC kidneys, and decreased in CR kidneys. Transmission electron microscopy demonstrated that HC kidneys showed severe abnormal mitochondrial morphology with fewer autolysosomes, while CR kidneys exhibited normal mitochondrial morphology with numerous autolysosomes. The level of 8-hydroxydeoxyguanosine was increased in HC kidneys and decreased in CR kidneys. Markers of aging, such as p16 and senescence-associated-galactosidase, were increased significantly in the HC group and decreased significantly in the CR group. The study firstly suggests that HC diet inhibits renal autophagy and aggravates renal oxidative damage and aging, while CR enhances renal autophagy and ameliorates oxidative damage and aging in the kidneys.

[Effective interventions to prevent child injuries: a review of the literature].

Science.gov (United States)

Nguyen Thanh, Viêt; Clément, Juliette; Thélot, Bertrand; Richard, Jean-Baptiste; Lamboy, Béatrice; Arwidson, Pierre

2015-01-01

Child injuries represent an important public health problem. The aim of this paper is to review the current scientific knowledge on interventions designed to prevent child injuries. The current state of knowledge in this area was assessed by means of a specific method involving a review of literature reviews and a classification of health promotion interventions identified in these reviews (rapid reviews). We found a large number of effective or promising programmes devoted to the prevention of the most common child injuries: drowning, burns, falls, poisoning, electrocution, sports and leisure injuries. Some interventions are based on environmental measures, while others are educational or use law and regulatory processes. Some are primary prevention measures, others are secondary prevention measures, while others are multidimensional and can effectively reduce several types of injuries. For example, home safety education and provision of safety equipment, or home-based parenting interventions, can have an impact on injury rates. These findings present a number of limitations due to the marked diversity of the quality of the documents reviewed. It should also be stressed that interventions that are not listed in this article are not necessarily ineffective: they may simply lack a rigorous evaluation enabling them to be identified in our review.

Urinary tract injuries in laparoscopic hysterectomy: a systematic review.

Science.gov (United States)

Adelman, Marisa R; Bardsley, Tyler R; Sharp, Howard T

2014-01-01

The aim of this review was to estimate the incidence of urinary tract injuries associated with laparoscopic hysterectomy and describe the long-term sequelae of these injuries and the impact of early recognition. Studies were identified by searching the PubMed database, spanning the last 10 years. The key words "ureter" or "ureteral" or "urethra" or "urethral" or "bladder" or "urinary tract" and "injury" and "laparoscopy" or "robotic" and "gynecology" were used. Additionally, a separate search was done for "routine cystoscopy" and "gynecology." The inclusion criteria were published articles of original research referring to urologic injuries occurring during either laparoscopic or robotic surgery for gynecologic indications. Only English language articles from the past 10 years were included. Studies with less than 100 patients and no injuries reported were excluded. No robotic series met these criteria. A primary search of the database yielded 104 articles, and secondary cross-reference yielded 6 articles. After reviewing the abstracts, 40 articles met inclusion criteria and were reviewed in their entirety. Of those 40 articles, 3 were excluded because of an inability to extract urinary tract injuries from total injuries. Statistical analysis was performed using a generalized linear mixed effects model. The overall urinary tract injury rate for laparoscopic hysterectomy was 0.73%. The bladder injury rate ranged from 0.05% to 0.66% across procedure types, and the ureteral injury rate ranged from 0.02% to 0.4% across procedure type. In contrast to earlier publications, which cited unacceptably high urinary tract injury rates, laparoscopic hysterectomy appears to be safe regarding the bladder and ureter. Copyright © 2014 AAGL. Published by Elsevier Inc. All rights reserved.

Mitochondrial Metabolism in Aging Heart

Science.gov (United States)

Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

2016-01-01

Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

Cerebral energy metabolism during induced mitochondrial dysfunction

DEFF Research Database (Denmark)

Nielsen, T H; Bindslev, TT; Pedersen, S M

2013-01-01

In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes...... in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

Injuries in karate: systematic review.

Science.gov (United States)

Thomas, Roger E; Ornstein, Jodie

2018-05-22

to identify all studies of Karate injuries and assess injury rates, types, location, and causes. Six electronic and four grey literature databases were searched. Two reviewers independently assessed titles/abstracts, abstracted data and assessed risk-of-bias with the Newcastle-Ottawa scale. Average injury rates/1000AE (AE = athletic-encounter) and/1000minutesAE, injury location and type weighted by study size were calculated. In competitions rates of injury/1000AE and/1000 minutesAE were similar for males (111.4/1000AE, 75.4/1000 minAE) and females (105.8/1000AE, 72.8/1000 minAE). Location of injury rates/1000AE for males were 44.0 for head/neck, 11.9 lower extremities, 8.1 torso and 5.4 upper extremities and were similar for females: 41.2 head/neck, 12.4 lower extremities, 9.1 torso and 6.3 upper extremities. Injury rates varied widely by study. Rates/1000AE for type of injury were contusions/abrasions/lacerations/bruises/tooth avulsion for males (68.1) and females (30.4); hematomas/bleeding/epistaxis males (11.4) and females (12.1); strains/sprains males (3.5) and females (0.1); dislocations males (2.9) and females (0.9); concussions males (2.5) and females (3.9); and fractures males (2.9) and females (1.4). Punches were a more common mechanism of injury for males (59.8) than females (40.8) and kicks similar (males 19.7, females 21.7). Weighted averages were not calculated for weight class or belt colour because there were too few studies. Nineteen injury surveys reported annual injury rates from 30% to rates ten times higher but used different reporting methods. Studies provided no data to explain wide rate ranges. Studies need to adopt one injury definition, one data-collection form, and collect comprehensive data for each study for both training and competitions. More data are needed to measure the effect of weight, age and experience on injuries, rates and types of injury during training, and for competitors with high injury rates. RCTs are needed of

The impact of sharps injuries on student nurses: a systematic review.

Science.gov (United States)

Hambridge, Kevin; Nichols, Andrew; Endacott, Ruth

2016-10-27

The purpose of this review was to discover the impact of sharps injuries in the student nurse population. Much is known and reported about sharps injuries in registered nurses, but there has been a lack of published evidence regarding sharps injuries within the student nurse population. A systematic review of nursing, health and psychology databases was conducted. The limits set were publications between 1980 and 2014 in the English language. Studies were identified then, following a rigorous critical and quality appraisal with validated tools, were selected for the systematic review. A total of 40 articles met the inclusion criteria, reporting studies conducted in 18 countries. Psychological and physical impacts of sharps injuries in student nurses were reported, such as fear, anxiety and depression, although these impacts were not quantified using a validated instrument. The impact of sharps injuries can be severe, both psychological and physical. This systematic review shows that further research is needed into this, especially in under-researched areas such as the UK, to establish the impact of sharps injuries within this population. Further research would also aid the education and prevention of this harmful problem. The review also emphasises the psychological issues relating to sharps injuries, the impact these can have on individuals and the support and counselling that student nurses require after injury. These findings highlight the potential psychological issues that can result from sharps injuries in this population.

Qing Dai attenuates nonsteroidal anti-inflammatory drug-induced mitochondrial reactive oxygen species in gastrointestinal epithelial cells.

Science.gov (United States)

Saito, Rie; Tamura, Masato; Matsui, Hirofumi; Nagano, Yumiko; Suzuki, Hideo; Kaneko, Tsuyoshi; Mizokami, Yuji; Hyodo, Ichinosuke

2015-01-01

Treatments with nonsteroidal anti-inflammatory drugs (NSAIDs) have increased the number of patients with gastrointestinal complications. Qing Dai has been traditionally used in Chinese herbal medicine for various inflammatory diseases such as ulcerative colitis. We previously reported that Qing Dai suppressed inflammations by scavenging reactive oxygen species (ROS) in ulcerative colitis patients. Thus, Qing Dai can attenuate the production of ROS, which play an important role in NSAID-induced gastrointestinal injuries. In this study, we aimed to elucidate whether Qing Dai decreased mitochondrial ROS production in NSAID-treated gastrointestinal cells by examining cellular injury, mitochondrial membrane potentials, and ROS production with specific fluorescent indicators. We also performed electron paramagnetic resonance measurement in isolated mitochondria with a spin-trapping reagent (CYPMPO or DMPO). Treatments with indomethacin and aspirin induced cellular injury and mitochondrial impairment in the gastrointestinal cells. Under these conditions, mitochondrial alterations were observed on electron microscopy. Qing Dai prevented these complications by suppressing ROS production in gastrointestinal cells. These results indicate that Qing Dai attenuated the ROS production from the NSAID-induced mitochondrial alteration in the gastrointestinal epithelial cells. Qing Dai treatment may be considered effective for the prevention NSAID-induced gastrointestinal injury.

Epidemiological Review of Injury in Pre-Professional Ballet Dancers.

Science.gov (United States)

Caine, Dennis; Goodwin, Brett J; Caine, Caroline G; Bergeron, Glen

2015-12-01

The objective of this study was to provide an epidemiological review of the literature concerning ballet injuries affecting pre-professional ballet dancers. The literature search was limited to published peer-reviewed reports and involved an extensive examination of Scopus, SPORTDiscus, and CINAHL. The following search terms were used in various combinations: ballet, injury, epidemiology, risk factor, pre-professional, and intervention. Additional citations were located using the ancestry approach. Unlike some other athletic activities that have been the focus of recent intervention research, there is a paucity of intervention and translational research in pre-professional ballet, and sample sizes have often been small and have not accounted for the multivariate nature of ballet injury. Exposure-based injury rates in this population appear similar to those reported for professional ballet dancers and female gymnasts. A preponderance of injuries affect the lower extremity of these dancers, with sprains and strains being the most frequent type of injury reported. The majority of injuries appear to be overuse in nature. Injury risk factors have been tested in multiple studies and indicate a variety of potential injury predictors that may provide useful guidance for future research.

[Injuries in the Martial Arts Judo, Taekwondo and Wrestling - A Systematic Review].

Science.gov (United States)

Jäggi, U; Joray, C P; Brülhart, Y; Luijckx, E; Rogan, S

2015-12-01

Martial arts such as judo, taekwondo and wrestling are regulated, usually athletic duels. The aim is to score better than your opponent or to win. As with any type of sport, athletes in martial arts sustain minor and major injuries, which may have many negative consequences. In addition, sports injuries and their rehabilitation generate high costs to the healthcare system. In contrast to the FIFA 11+ warm-up program, no preventive programs have been postulated for injury prevention in these martial arts. Therefore, the aim of this systematic review was to summarise the latest research findings and to evaluate whether initial recommendations can be given for the reduction of injuries in the martial arts judo, wrestling and taekwondo. To gain an overview of the latest research findings, we searched for systematic reviews in PEDro, PubMed, Cochrane and the internet search engine Google Scholar. The methodological quality of these reviews was assessed using the Critical Appraisal Tool for a Systematic Review (CASP), and data was extracted on the risk of injury, injury location and injury type. It was found that all three review articles are of low to moderate methodological quality. Regarding injury location, it became evident that the extremities are particularly vulnerable to injury in all three martial arts. Effusion was observed to be the most common type of injury. Due to the moderate methodological quality and the injury type of effusion, it is not possible to formulate recommendations for injury prevention. Moreover, uniform definitions should be developed to describe sports injuries. © Georg Thieme Verlag KG Stuttgart · New York.

Sexuality following trauma injury: A literature review

OpenAIRE

Kylie Marie Connell; Rosemary Coates; Fiona Melanie Wood

2014-01-01

Restoration of the quality of life (QoL) of trauma injury survivors is the aim of trauma rehabilitation. It is generally acknowledged that sexuality is an important component of QoL; however, rehabilitation services frequently fall short of including sexuality as a matter of routine. The literature was reviewed to examine the experiences of trauma survivors from three groups: spinal cord injury (SCI), traumatic brain injury (TBI) and burns. The focus was on the impact of trauma on the QoL to ...

Injury epidemiology in Iran: a systematic review

Directory of Open Access Journals (Sweden)

Saber Azami-Aghdash

2017-01-01

Full Text Available Background: Injuries are the second greatest cause of mortality in Iran. Information about the epidemiological pattern of injuries is effective in decision-making. In this regard, the aim of the current study is to elaborate on the epidemiology of injuries in Iran through a systematic review. Methods: Required data were collected searching the following key words and their Persian equivalents; trauma, injury, accident, epidemiology, prevalence, Pattern, etiology, risk factors and Iran. The following databases were searched: Google Scholar, PubMed, Scopus, MagIran, Iranian scientific information database (SID and Iran Medex. Some of the relevant journals and web sites were searched manually. The lists of references from the selected articles were also investigated. We have also searched the gray literature and consulted some experts. Results: Out of 2747 retrieved articles, 25 articles were finally included in the review. A total of 3234481 cases have been investigated. Mean (SD age among these cases was 30 (17.4 years. Males comprised 75.7% of all the patients. Only 31.1% of patients were transferred to hospital by ambulance. The most common mechanism of injuries was road traffic accidents (50.1%, followed by falls (22.3%. In road traffic accidents, motorcyclists have accounted for the majority of victims (45%. Roads were the most common accident scene for the injuries (57.5%. The most common injuries were to the head and neck. (47.3%. The mean (SD Injury Severity Score (ISS was 8.1(8.6%. The overall case-fatality proportion was 3.8% and 75% of all the mortalities related to road traffic accidents. Conclusions: The main priorities in reducing the burden of injuries include: the young, male target group, improving pre-hospital and ambulance services, preventing road traffic accidents, improving road safety and the safety of motorcyclists (compulsory helmet use, safer vehicles, dedicated motorcycle lanes.

Review article: Methodology for the 'rapid review' series on musculoskeletal injuries in the emergency department.

Science.gov (United States)

Strudwick, Kirsten; McPhee, Megan; Bell, Anthony; Martin-Khan, Melinda; Russell, Trevor

2018-02-01

Musculoskeletal injuries are a common presentation to the ED, with significant costs involved in the management of these injuries, variances in care within the ED and associated morbidity. A series of rapid review papers were completed to guide best practice for the assessment and management of common musculoskeletal injuries presenting to the ED. This paper presents the methodology used across the rapid reviews. PubMed, CINAHL, EMBASE, TRIP and the grey literature, including relevant organisational websites, were searched in 2015. The search was repeated consistently for each topic area (injuries of the foot and ankle, knee, hand and wrist, elbow, shoulder, lumbar spine and cervical spine). English-language primary studies, systematic reviews and guidelines that were published in the last 10 years and addressed acute musculoskeletal injury management were considered for inclusion. Data extraction of each included article was conducted, followed by a quality appraisal. The extracted data from each article was synthesised to group similar evidence together. For each rapid review, the evidence has been organised in a way that a clinician can direct their attention to a specific component of the clinical cycle of care in the ED, such as the assessment, diagnostic tests, management and follow-up considerations from ED. The series of rapid reviews are designed to foster evidence-based practice within the ED, targeting the injuries most commonly presenting. The reviews provide clinicians in EDs with rapid access to the best current evidence, which has been synthesised and organised to assist decision-making. © 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Exercise and ankle sprain injuries: a comprehensive review.

Science.gov (United States)

Calatayud, Joaquin; Borreani, Sebastien; Colado, Juan Carlos; Flandez, Jorge; Page, Phil; Andersen, Lars L

2014-02-01

Ankle sprains are common in team sports and sports played on courts, and often result in structural and functional alterations that lead to a greater reinjury risk. Specific exercises are often used to promote neuromuscular improvements in the prevention and rehabilitation of ankle injuries. This literature review summarizes the neuromuscular characteristics of common ankle sprains and the effectiveness of exercise as an intervention for improving neuromuscular function and preventing reinjury. Our review found that appropriate exercise prescription can increase static and dynamic balance and decrease injury recurrence. In particular, the addition of dynamic activities in the exercise program can be beneficial because of the anticipatory postural adjustments identified as a key factor in the injury mechanism.

Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of Diabetic Nephropathy.

Science.gov (United States)

Schiffer, Tomas A; Friederich-Persson, Malou

2017-01-01

The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy.

Sport Injuries Sustained by Athletes with Disability: A Systematic Review

OpenAIRE

Weiler, Richard; Van Mechelen, Willem; Fuller, Colin; Verhagen, Evert

2016-01-01

Background Fifteen percent of the world?s population live with disability, and many of these individuals choose to play sport. There are barriers to sport participation for athletes with disability and sports injury can greatly impact on daily life, which makes sports injury prevention additionally important. Objective The purpose of this review is to systematically review the definitions, methodologies and injury rates in disability sport, which should assist future identification of risk fa...

Digital Imaging Analysis for the Study of Endotoxin-Induced Mitochondrial Ultrastructure Injury

Directory of Open Access Journals (Sweden)

Mandar S. Joshi

2000-01-01

Full Text Available Primary defects in mitochondrial function have been implicated in over 100 diverse diseases. In situ, mitochondria possess unique and well-defined morphology in normal healthy cells, but diseases linked to defective mitochondrial function are characterized by the presence of morphologically abnormal and swollen mitochondria with distorted cristae. In situ study of mitochondrial morphology is established as an indicator of mitochondrial health but thus far assessments have been via subjective evaluations by trained observers using discontinuous scoring systems. Here we investigated the value of digital imaging analysis to provide for unbiased, reproducible, and convenient evaluations of mitochondrial ultrastructure. Electron photomicrographs of ileal mucosal mitochondria were investigated using a scoring system previously described by us, and also analyzed digitally by using six digital parameters which define size, shape, and electron density characteristics of over 700 individual mitochondria. Statistically significant changes in mitochondrial morphology were detected in LPS treated animals relative to vehicle control using both the subjective scoring system and digital imaging parameters (p < 0:05. However, the imaging approach provided convenient and high throughput capabilities and was easily automated to remove investigator influences. These results illustrate significant changes in ileal mucosal mitochondrial ultrastructure during sepsis and demonstrate the value of digital imaging technology for routine assessments in this setting.

Roles of Oxidative Stress, Apoptosis, PGC-1α and Mitochondrial Biogenesis in Cerebral Ischemia

Directory of Open Access Journals (Sweden)

Ding-I Yang

2011-10-01

Full Text Available The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ co-activator 1α (PGC1-α. PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis.

Mitochondrial shaping cuts.

Science.gov (United States)

Escobar-Henriques, Mafalda; Langer, Thomas

2006-01-01

A broad range of cellular processes are regulated by proteolytic events. Proteolysis has now also been established to control mitochondrial morphology which results from the balanced action of fusion and fission. Two out of three known core components of the mitochondrial fusion machinery are under proteolytic control. The GTPase Fzo1 in the outer membrane of mitochondria is degraded along two independent proteolytic pathways. One controls mitochondrial fusion in vegetatively growing cells, the other one acts upon mating factor-induced cell cycle arrest. Fusion also depends on proteolytic processing of the GTPase Mgm1 by the rhomboid protease Pcp1 in the inner membrane of mitochondria. Functional links of AAA proteases or other proteolytic components to mitochondrial dynamics are just emerging. This review summarises the current understanding of regulatory roles of proteolytic processes for mitochondrial plasticity.

Adiponectin alleviates genioglossal mitochondrial dysfunction in rats exposed to intermittent hypoxia.

Directory of Open Access Journals (Sweden)

Hanpeng Huang

Full Text Available Genioglossal dysfunction is involved in the pathophysiology of obstructive sleep apnea hypoxia syndrome (OSAHS characterized by nocturnal chronic intermittent hypoxia (CIH. The pathophysiology of genioglossal dysfunction and possible targeted pharmacotherapy for alleviation of genioglossal injury in CIH require further investigation.Rats in the control group were exposed to normal air, while rats in the CIH group and CIH+adiponectin (AD group were exposed to the same CIH condition (CIH 8 hr/day for 5 successive weeks. Furthermore, rats in CIH+AD group were administrated intravenous AD supplementation at the dosage of 10 µg, twice a week for 5 consecutive weeks. We found that CIH-induced genioglossus (GG injury was correlated with mitochondrial dysfunction, reduction in the numbers of mitochondrias, impaired mitochondrial ultrastructure, and a reduction in type I fibers. Compared with the CIH group, impaired mitochondrial structure and function was significantly improved and a percentage of type I fiber was elevated in the CIH+AD group. Moreover, compared with the control group, the rats' GG in the CIH group showed a significant decrease in phosphorylation of LKB1, AMPK, and PGC1-α, whereas there was significant rescue of such reduction in phosphorylation within the CIH+AD group.CIH exposure reduces mitochondrial biogenesis and impairs mitochondrial function in GG, while AD supplementation increases mitochondrial contents and alleviates CIH-induced mitochondrial dysfunction possibly through the AMPK pathway.

Review of liver injury associated with dietary supplements.

Science.gov (United States)

Stickel, Felix; Kessebohm, Kerstin; Weimann, Rosemarie; Seitz, Helmut K

2011-05-01

Dietary supplements (DS) are easily available and increasingly used, and adverse hepatic reactions have been reported following their intake. To critically review the literature on liver injury because of DSs, delineating patterns and mechanisms of injury and to increase the awareness towards this cause of acute and chronic liver damage. Studies and case reports on liver injury specifically because of DSs published between 1990 and 2010 were searched in the PubMed and EMBASE data bases using the terms 'dietary/nutritional supplements', 'adverse hepatic reactions', 'liver injury'; 'hepatitis', 'liver failure', 'vitamin A' and 'retinoids', and reviewed for yet unidentified publications. Significant liver injury was reported after intake of Herbalife and Hydroxycut products, tea extracts from Camellia sinensis, products containing usnic acid and high contents of vitamin A, anabolic steroids and others. No uniform pattern of hepatotoxicity has been identified and severity may range from asymptomatic elevations of serum liver enzymes to hepatic failure and death. Exact estimates on how frequent adverse hepatic reactions occur as a result of DSs cannot be provided. Liver injury from DSs mimicking other liver diseases is increasingly recognized. Measures to reduce risk include tighter regulation of their production and distribution and increased awareness of users and professionals of the potential risks. © 2011 John Wiley & Sons A/S.

A Review of Occupational Injury Research In Malaysia.

Science.gov (United States)

Ganesh, C S; Krishnan, R

2016-06-01

A literature review of 16 papers on occupational injury research in Malaysia published during a 13-year period from 2000-2013 was carried out. The objective of this review and article selection was based on relevance to the research theme and mention of areas for future research. Most of the publications have focused on descriptive epidemiology, management practices, worker's knowledge, attitude, training, and rehabilitation services. The transportation, agriculture and construction sectors were found to be the most hazardous sectors and would benefit the most from Occupational Safety & Health (OSH) research and interventions. There is a strong need to develop a national injury surveillance system and also a mechanism to ensure adherence to the Occupational Safety & Health Act(OSHA) 1994. Detailed description and identification of risk factors for occupational injury in the environment, including machinery and equipment used was generally lacking. Future research on occupational injury should focus on surveillance to determine the magnitude of occupational injuries, determination of risk factors, identifying costeffective interventions (such as enforcement of OSHA regulations), and assessment of rehabilitation services. Relevant government agencies, universities, corporate sector and occupational safety organizations need to play a proactive role in identifying priority areas and research capacity building. Funding for occupational injury should be commensurate with the magnitude of the problem.

Mitochondrial quality control in cardiac diseases.

Directory of Open Access Journals (Sweden)

Juliane Campos

2016-10-01

Full Text Available Disruption of mitochondrial homeostasis is a hallmark of cardiac diseases. Therefore, maintenance of mitochondrial integrity through different surveillance mechanisms is critical for cardiomyocyte survival. In this review, we discuss the most recent findings on the central role of mitochondrial quality control processes including regulation of mitochondrial redox balance, aldehyde metabolism, proteostasis, dynamics and clearance in cardiac diseases, highlighting their potential as therapeutic targets.

The Mitochondrial Calcium Uniporter Selectively Matches Metabolic Output to Acute Contractile Stress in the Heart

Directory of Open Access Journals (Sweden)

Jennifer Q. Kwong

2015-07-01

Full Text Available In the heart, augmented Ca2+ fluxing drives contractility and ATP generation through mitochondrial Ca2+ loading. Pathologic mitochondrial Ca2+ overload with ischemic injury triggers mitochondrial permeability transition pore (MPTP opening and cardiomyocyte death. Mitochondrial Ca2+ uptake is primarily mediated by the mitochondrial Ca2+ uniporter (MCU. Here, we generated mice with adult and cardiomyocyte-specific deletion of Mcu, which produced mitochondria refractory to acute Ca2+ uptake, with impaired ATP production, and inhibited MPTP opening upon acute Ca2+ challenge. Mice lacking Mcu in the adult heart were also protected from acute ischemia-reperfusion injury. However, resting/basal mitochondrial Ca2+ levels were normal in hearts of Mcu-deleted mice, and mitochondria lacking MCU eventually loaded with Ca2+ after stress stimulation. Indeed, Mcu-deleted mice were unable to immediately sprint on a treadmill unless warmed up for 30 min. Hence, MCU is a dedicated regulator of short-term mitochondrial Ca2+ loading underlying a “fight-or-flight” response that acutely matches cardiac workload with ATP production.

Injuries in epilepsy: a review of its prevalence, risk factors, type of injuries and prevention

Directory of Open Access Journals (Sweden)

Jose Tellez-Zenteno

2009-12-01

hospitalizations could be related with the severity of the injury. This article reviews the best available epidemiological information about injuries, including incidence and risk factors. Also this article reviews information about specific types of injuries such as fractures, burns, concussions, dislocations, etc. Information about accidents in people with epilepsy is also discussed.

Mitochondrial Nucleoid: Shield and Switch of the Mitochondrial Genome

Science.gov (United States)

2017-01-01

Mitochondria preserve very complex and distinctively unique machinery to maintain and express the content of mitochondrial DNA (mtDNA). Similar to chromosomes, mtDNA is packaged into discrete mtDNA-protein complexes referred to as a nucleoid. In addition to its role as a mtDNA shield, over 50 nucleoid-associated proteins play roles in mtDNA maintenance and gene expression through either temporary or permanent association with mtDNA or other nucleoid-associated proteins. The number of mtDNA(s) contained within a single nucleoid is a fundamental question but remains a somewhat controversial issue. Disturbance in nucleoid components and mutations in mtDNA were identified as significant in various diseases, including carcinogenesis. Significant interest in the nucleoid structure and its regulation has been stimulated in relation to mitochondrial diseases, which encompass diseases in multicellular organisms and are associated with accumulation of numerous mutations in mtDNA. In this review, mitochondrial nucleoid structure, nucleoid-associated proteins, and their regulatory roles in mitochondrial metabolism are briefly addressed to provide an overview of the emerging research field involving mitochondrial biology. PMID:28680532

Factors predicting outcome in whiplash injury: a systematic meta-review of prognostic factors.

Science.gov (United States)

Sarrami, Pooria; Armstrong, Elizabeth; Naylor, Justine M; Harris, Ian A

2017-03-01

Whiplash injuries are among the leading injuries related to car crashes and it is important to determine the prognostic factors that predict the outcome of patients with these injuries. This meta-review aims to identify factors that are associated with outcome after acute whiplash injury. A systematic search for all systematic reviews on outcome prediction of acute whiplash injury was conducted across several electronic databases. The search was limited to publications in English, and there were no geographical or time of publication restrictions. Quality appraisal was conducted with A Measurement Tool to Assess Systematic Reviews. The initial search yielded 207 abstracts; of these, 195 were subsequently excluded by topic or method. Twelve systematic reviews with moderate quality were subsequently included in the analysis. Post-injury pain and disability, whiplash grades, cold hyperalgesia, post-injury anxiety, catastrophizing, compensation and legal factors, and early healthcare use were associated with continuation of pain and disability in patients with whiplash injury. Post-injury magnetic resonance imaging or radiographic findings, motor dysfunctions, or factors related to the collision were not associated with continuation of pain and disability in patients with whiplash injury. Evidence on demographic and three psychological factors and prior pain was conflicting, and there is a shortage of evidence related to the significance of genetic factors. This meta-review suggests an association between initial pain and anxiety and the outcome of acute whiplash injury, and less evidence for an association with physical factors. Level 1.

Common Ice Hockey Injuries and Treatment: A Current Concepts Review.

Science.gov (United States)

Mosenthal, William; Kim, Michael; Holzshu, Robert; Hanypsiak, Bryan; Athiviraham, Aravind

Injuries are common in ice hockey, a contact sport where players skate at high speeds on a sheet of ice and shoot a vulcanized rubber puck in excess of one hundred miles per hour. This article reviews the diagnoses and treatment of concussions, injuries to the cervical spine, and lower and upper extremities as they pertain to hockey players. Soft tissue injury of the shoulder, acromioclavicular joint separation, glenohumeral joint dislocation, clavicle fractures, metacarpal fractures, and olecranon bursitis are discussed in the upper-extremity section of the article. Lower-extremity injuries reviewed in this article include adductor strain, athletic pubalgia, femoroacetabular impingement, sports hernia, medial collateral and anterior cruciate ligament tears, skate bite, and ankle sprains. This review is intended to aid the sports medicine physician in providing optimal sports-specific care to allow their athlete to return to their preinjury level of performance.

Mitigating the risk of musculoskeletal injury: A systematic review of the most effective injury prevention strategies for military personnel.

Science.gov (United States)

Wardle, Sophie L; Greeves, Julie P

2017-11-01

To update the current injury prevention strategy evidence base for making recommendations to prevent physical training-related musculoskeletal injury. We conducted a systematic review to update the evidence base on injury prevention strategies for military personnel. Literature was systematically searched and extracted from five databases, and reported according to PRISMA guidelines. Sixty one articles meeting the inclusion criteria and published during the period 2008-2015 were selected for systematic review. The retrieved articles were broadly categorised into six injury prevention strategies; (1) conditioning, (2) footwear modifications, (3) bracing, (4) physical activity volume, (5) physical fitness, and (6) leadership/supervision/awareness. The majority of retrieved articles (n=37 (of 61) evaluated or systematically reviewed a conditioning intervention of some nature. However, the most well-supported strategies were related to reducing physical activity volume and improving leadership/supervision/awareness of injuries and injury prevention efforts. Several injury prevention strategies effectively reduce musculoskeletal injury rates in both sexes, and many show promise for utility with military personnel. However, further evaluation, ideally with prospective randomised trials, is required to establish the most effective injury prevention strategies, and to understand any sex-specific differences in the response to these strategies. Copyright © 2017. Published by Elsevier Ltd.

Incidence and Prevalence of Musculoskeletal Injury in Ballet: A Systematic Review.

Science.gov (United States)

Smith, Preston J; Gerrie, Brayden J; Varner, Kevin E; McCulloch, Patrick C; Lintner, David M; Harris, Joshua D

2015-07-01

Most published studies on injuries in the ballet dancer focus on the lower extremity. The rigors of this activity require special training and care. By understanding prevalence and injury pattern to the musculoskeletal system, targeted prevention and treatment for this population can be developed. To determine the incidence and prevalence of musculoskeletal injuries in ballet. Systematic review; Level of evidence, 4. A systematic review registered with PROSPERO was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Level 1 through 4 evidence studies reporting incidence of musculoskeletal injuries in male and female ballet dancers were included, with the numbers and types of injuries extracted from each. Injury rates were recorded and calculated based on professional status, sex, and nature of injury. Incidence was defined as number of injuries sustained over a specific time. Prevalence was defined as proportion of subjects with an injury at a given point in time. The studies analyzed reported injury incidence or prevalence in more than 1365 amateur and 900 professional dancers. The mean age was 16.2 years among amateur and 27.0 years among professional dancers. The incidence of injury among amateur dancers was 0.99 and 1.09 injuries per 1000 dance hours in males and females, respectively; 75% of injuries were overuse, with similar rates among males and females. In professional dancers, the incidence of injury was 1.06 and 1.46 injuries per 1000 dance hours in males and females, respectively, and 64% of female injuries were overuse, compared with 50% in males (P ballet dancers is 0.97 and 1.24 injuries per 1000 dance hours, respectively. The majority are overuse in both amateur and professional dancers, with amateur ballet dancers showing a higher proportion of overuse injuries than professionals (P < .001). Male professional dancers show a higher proportion of traumatic injuries, accounting for half of their

Mitochondrial matters: Mitochondrial bottlenecks, self-assembling structures, and entrapment in the female germline

Directory of Open Access Journals (Sweden)

Florence L. Marlow

2017-05-01

Full Text Available Mitochondrial replacement therapy, a procedure to generate embryos with the nuclear genome of a donor mother and the healthy mitochondria of a recipient egg, has recently emerged as a promising strategy to prevent transmission of devastating mitochondrial DNA diseases and infertility. The procedure may produce an embryo that is free of diseased mitochondria. A recent study addresses important fundamental questions about the mechanisms underlying maternal inheritance and translational questions regarding the transgenerational effectiveness of this promising therapeutic strategy. This review considers recent advances in our understanding of maternal inheritance of mitochondria, implications for fertility and mitochondrial disease, and potential roles for the Balbiani body, an ancient oocyte structure, in mitochondrial selection in oocytes, with emphasis on therapies to remedy mitochondrial disorders.

Cardiovascular Mitochondrial Dysfunction Induced by Cocaine: Biomarkers and Possible Beneficial Effects of Modulators of Oxidative Stress

Directory of Open Access Journals (Sweden)

Manuela Graziani

2017-01-01

Full Text Available Cocaine abuse has long been known to cause morbidity and mortality due to its cardiovascular toxic effects. The pathogenesis of the cardiovascular toxicity of cocaine use has been largely reviewed, and the most recent data indicate a fundamental role of oxidative stress in cocaine-induced cardiovascular toxicity, indicating that mitochondrial dysfunction is involved in the mechanisms of oxidative stress. The comprehension of the mechanisms involving mitochondrial dysfunction could help in selecting the most appropriate mitochondria injury biological marker, such as superoxide dismutase-2 activity and glutathionylated hemoglobin. The potential use of modulators of oxidative stress (mitoubiquinone, the short-chain quinone idebenone, and allopurinol in the treatment of cocaine cardiotoxic effects is also suggested to promote further investigations on these potential mitochondria-targeted antioxidant strategies.

Mitochondrial Fusion Proteins and Human Diseases

Directory of Open Access Journals (Sweden)

Michela Ranieri

2013-01-01

Full Text Available Mitochondria are highly dynamic, complex organelles that continuously alter their shape, ranging between two opposite processes, fission and fusion, in response to several stimuli and the metabolic demands of the cell. Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1 and 2 (MFN2, located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1, in the inner membrane. An expanding number of degenerative disorders are associated with mutations in the genes encoding MFN2 and OPA1, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. While these disorders can still be considered rare, defective mitochondrial dynamics seem to play a significant role in the molecular and cellular pathogenesis of more common neurodegenerative diseases, for example, Alzheimer’s and Parkinson’s diseases. This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. We also review the literature describing the main disorders associated with the disruption of mitochondrial fusion.

The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep hypothermia and rewarming in rats.

Science.gov (United States)

Vogelaar, Pieter C; Roorda, Maurits; de Vrij, Edwin L; Houwertjes, Martin C; Goris, Maaike; Bouma, Hjalmar; van der Graaf, Adrianus C; Krenning, Guido; Henning, Robert H

2018-04-11

Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats. Human proximal tubule cell viability was assessed following exposure to H/R for 48/4 h in the presence of various 6-hydroxychromanols. Selected compounds (SUL-109, SUL-121) or vehicle were administered to ketamine-anaesthetized male Wistar rats (IV 135 µg/kg/h) undergoing H/R at 15°C for 3 h followed by rewarming and normothermia for 1 h. Metabolic parameters and body temperature were measured throughout. In addition, renal function, renal injury, histopathology and mitochondrial fitness were assessed. H/R injury in vitro lowered cell viability by 94 ± 1%, which was counteracted dose-dependently by multiple 6-hydroxychomanols derivatives. In vivo, H/R in rats showed kidney injury molecule 1 expression in the kidney and tubular dilation, accompanied by double-strand DNA breaks and protein nitrosylation. SUL-109 and SUL-121 ameliorated tubular kidney damage, preserved mitochondrial mass and maintained cortical adenosine 5'-triphosphate (ATP) levels, although SUL-121 did not reduce protein nitrosylation. The substituted 6-hydroxychromanols SUL-109 and SUL-121 ameliorate kidney injury during in vivo H/R by preserving mitochondrial mass, function and ATP levels. In addition, both 6-hydroxychromanols

Risk factors of recurrent hamstring injuries: A systematic review

NARCIS (Netherlands)

H.M. de Visser (H.); M. Reijman (Max); M.P. Heijboer (Rien); P.K. Bos (Koen)

2012-01-01

textabstractBackground Although recurrent hamstring injury is a frequent problem with a significant impact on athletes, data on factors determining the risk for a recurrent hamstring injury are scarce. Objective To systematically review the literature and provide an overview of risk factors for

Ginsenoside Rg1 improves ischemic brain injury by balancing ...

African Journals Online (AJOL)

Ginsenoside Rg1 improves ischemic brain injury by balancing mitochondrial ... and autophagy-related proteins were determined by reat time-polymerase chain ... Treatment with autophagy inhibitors decreased the mitochondrial protective ...

Respiratory mechanics in brain injury: A review.

Science.gov (United States)

Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

2016-02-04

Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilator-induced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients.

Ripk3 induces mitochondrial apoptosis via inhibition of FUNDC1 mitophagy in cardiac IR injury

Directory of Open Access Journals (Sweden)

Hao Zhou

2017-10-01

Full Text Available Ripk3-required necroptosis and mitochondria-mediated apoptosis are the predominant types of cell death that largely account for the development of cardiac ischemia reperfusion injury (IRI. Here, we explored the effect of Ripk3 on mitochondrial apoptosis. Compared with wild-type mice, the infarcted area in Ripk3-deficient (Ripk3-/- mice had a relatively low abundance of apoptotic cells. Moreover, the loss of Ripk3 protected the mitochondria against IRI and inhibited caspase9 apoptotic pathways. These protective effects of Ripk3 deficiency were relied on mitophagy activation. However, inhibition of mitophagy under Ripk3 deficiency enhanced cardiomyocyte and endothelia apoptosis, augmented infarcted area and induced microvascular dysfunction. Furthermore, ischemia activated mitophagy by modifying FUNDC1 dephosphorylation, which substantively engulfed mitochondria debris and cytochrome-c, thus blocking apoptosis signal. However, reperfusion injury elevated the expression of Ripk3 which disrupted FUNDC1 activation and abated mitophagy, increasing the likelihood of apoptosis. In summary, this study confirms the promotive effect of Ripk3 on mitochondria-mediated apoptosis via inhibition of FUNDC1-dependent mitophagy in cardiac IRI. These findings provide new insight into the roles of Ripk3-related necroptosis, mitochondria-mediated apoptosis and FUNDC1-required mitophagy in cardiac IRI.

Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells.

Science.gov (United States)

Granger, D L; Lehninger, A L

1982-11-01

Previous work has shown that injury of neoplastic cells by cytotoxic macrophages (CM) in cell culture is accompanied by inhibition of mitochondrial respiration. We have investigated the nature of this inhibition by studying mitochondrial respiration in CM-injured leukemia L1210 cells permeabilized with digitonin. CM-induced injury affects the mitochondrial respiratory chain proper. Complex I (NADH-coenzyme Q reductase) and complex II (succinate-coenzyme Q reductase) are markedly inhibited. In addition a minor inhibition of cytochrome oxidase was found. Electron transport from alpha-glycerophosphate through the respiratory chain to oxygen is unaffected and permeabilized CM-injured L1210 cells oxidizing this substrate exhibit acceptor control. However, glycerophosphate shuttle activity was found not to occur within CM-injured or uninjured L1210 cells in culture hence, alpha-glycerophosphate is apparently unavailable for mitochondrial oxidation in the intact cell. It is concluded that the failure of respiration of intact neoplastic cells injured by CM is caused by the nearly complete inhibition of complexes I and II of the mitochondrial electron transport chain. The time courses of CM-induced electron transport inhibition and arrest of L1210 cell division are examined and the possible relationship between these phenomena is discussed.

Mitochondrial Roles and Cytoprotection in Chronic Liver Injury

Directory of Open Access Journals (Sweden)

Davide Degli Esposti

2012-01-01

Full Text Available The liver is one of the richest organs in terms of number and density of mitochondria. Most chronic liver diseases are associated with the accumulation of damaged mitochondria. Hepatic mitochondria have unique features compared to other organs' mitochondria, since they are the hub that integrates hepatic metabolism of carbohydrates, lipids and proteins. Mitochondria are also essential in hepatocyte survival as mediator of apoptosis and necrosis. Hepatocytes have developed different mechanisms to keep mitochondrial integrity or to prevent the effects of mitochondrial lesions, in particular regulating organelle biogenesis and degradation. In this paper, we will focus on the role of mitochondria in liver physiology, such as hepatic metabolism, reactive oxygen species homeostasis and cell survival. We will also focus on chronic liver pathologies, especially those linked to alcohol, virus, drugs or metabolic syndrome and we will discuss how mitochondria could provide a promising therapeutic target in these contexts.

Mitochondrial DNA and Cancer Epidemiology Workshop

Science.gov (United States)

A workshop to review the state-of-the science in the mitochondrial DNA field and its use in cancer epidemiology, and to develop a concept for a research initiative on mitochondrial DNA and cancer epidemiology.

Nintendo related injuries and other problems: review.

Science.gov (United States)

Jalink, Maarten B; Heineman, Erik; Pierie, Jean-Pierre E N; ten Cate Hoedemaker, Henk O

2014-12-16

To identify all reported cases of injury and other problems caused by using a Nintendo video gaming system. Review. Search of PubMed and Embase in June 2014 for reports on injuries and other problems caused by using a Nintendo gaming system. Most of the 38 articles identified were case reports or case series. Injuries and problems ranged from neurological and psychological to surgical. Traditional controllers with buttons were associated with tendinitis of the extensor of the thumb. The joystick on the Nintendo 64 controller was linked to palmar ulceration. The motion sensitive Wii remote was associated with musculoskeletal problems and various traumas. Most problems are mild and prevalence is low. The described injuries were related to the way the games are controlled, which varies according to the video game console. © Jalink et al 2014.

Progesterone induces neuroprotection following reperfusion-promoted mitochondrial dysfunction after focal cerebral ischemia in rats.

Science.gov (United States)

Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena

2017-06-01

Organelle damage and increases in mitochondrial permeabilization are key events in the development of cerebral ischemic tissue injury because they cause both modifications in ATP turnover and cellular apoptosis/necrosis. Early restoration of blood flow and improvement of mitochondrial function might reverse the situation and help in recovery following an onset of stroke. Mitochondria and related bioenergetic processes can be effectively used as pharmacological targets. Progesterone (P4), one of the promising neurosteroids, has been found to be neuroprotective in various models of neurological diseases, through a number of mechanisms. This influenced us to investigate the possible role of P4 in the mitochondria-mediated neuroprotective mechanism in an ischemic stroke model of rat. In this study, we have shown the positive effect of P4 administration on behavioral deficits and mitochondrial health in an ischemic stroke injury model of transient middle cerebral artery occlusion (tMCAO). After induction of tMCAO, the rats received an initial intraperitoneal injection of P4 (8 mg/kg body weight) or vehicle at 1 h post-occlusion followed by subcutaneous injections at 6, 12 and 18 h. Behavioral assessment for functional deficits included grip strength, motor coordination and gait analysis. Findings revealed a significant improvement with P4 treatment in tMCAO animals. Staining of isolated brain slices from P4-treated rats with 2,3,5-triphenyltetrazolium chloride (TTC) showed a reduction in the infarct area in comparison to the vehicle group, indicating the presence of an increased number of viable mitochondria. P4 treatment was also able to attenuate mitochondrial reactive oxygen species (ROS) production, as well as block the mitochondrial permeability transition pore (mPTP), in the tMCAO injury model. In addition, it was also able to ameliorate the altered mitochondrial membrane potential and respiration ratio in the ischemic animals, thereby suggesting that P4 has

Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis.

Science.gov (United States)

Zhou, Hao; Zhang, Ying; Hu, Shunying; Shi, Chen; Zhu, Pingjun; Ma, Qiang; Jin, Qinhua; Cao, Feng; Tian, Feng; Chen, Yundai

2017-08-01

The cardiac microvascular system, which is primarily composed of monolayer endothelial cells, is the site of blood supply and nutrient exchange to cardiomyocytes. However, microvascular ischemia/reperfusion injury (IRI) following percutaneous coronary intervention is a woefully neglected topic, and few strategies are available to reverse such pathologies. Here, we studied the effects of melatonin on microcirculation IRI and elucidated the underlying mechanism. Melatonin markedly reduced infarcted area, improved cardiac function, restored blood flow, and lower microcirculation perfusion defects. Histological analysis showed that cardiac microcirculation endothelial cells (CMEC) in melatonin-treated mice had an unbroken endothelial barrier, increased endothelial nitric oxide synthase expression, unobstructed lumen, reduced inflammatory cell infiltration, and less endothelial damage. In contrast, AMP-activated protein kinase α (AMPKα) deficiency abolished the beneficial effects of melatonin on microvasculature. In vitro, IRI activated dynamin-related protein 1 (Drp1)-dependent mitochondrial fission, which subsequently induced voltage-dependent anion channel 1 (VDAC1) oligomerization, hexokinase 2 (HK2) liberation, mitochondrial permeability transition pore (mPTP) opening, PINK1/Parkin upregulation, and ultimately mitophagy-mediated CMEC death. However, melatonin strengthened CMEC survival via activation of AMPKα, followed by p-Drp1 S616 downregulation and p-Drp1 S37 upregulation, which blunted Drp1-dependent mitochondrial fission. Suppression of mitochondrial fission by melatonin recovered VDAC1-HK2 interaction that prevented mPTP opening and PINK1/Parkin activation, eventually blocking mitophagy-mediated cellular death. In summary, this study confirmed that melatonin protects cardiac microvasculature against IRI. The underlying mechanism may be attributed to the inhibitory effects of melatonin on mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis via activation

Horse-related injuries in children - unmounted injuries are more severe: A retrospective review.

Science.gov (United States)

Wolyncewicz, Grace E L; Palmer, Cameron S; Jowett, Helen E; Hutson, John M; King, Sebastian K; Teague, Warwick J

2018-05-01

Horse-related injuries account for one quarter of all paediatric sports fatalities. It is not known whether the pattern of injury spectrum and severity differ between children injured whilst mounted, compared with those injured unmounted around horses. We aimed to identify any distinctions between the demographic features, spectrum and severity of injuries for mounted versus unmounted patients. Trauma registry data were reviewed for 505 consecutive paediatric patients (agedinjuries over a 16-year period. Patients were classified into mounted and unmounted groups, and demographics, injury spectrum, injury severity, and helmet usage compared using odds ratios and Wilcoxon rank-sum tests. More patients (56%) were injured in a private setting than in a sporting or supervised context (23%). Overall, head injuries were the most common horse-related injury. Mounted patients comprised 77% of the cohort. Mounted patients were more likely to sustain upper limb fractures or spinal injuries, and more likely to wear helmets. Unmounted were more likely to be younger males, and more likely to sustain facial or abdominal injuries. Strikingly, unmounted children had significantly more severe and critical Injury Severity Scores (OR 2.6; 95% CI 1.5, 4.6) and longer hospital stay (2.0days vs 1.1days; pinjury. Horse-related injuries in children are serious. Unmounted patients are distinct from mounted patients in terms of gender, age, likelihood of personal protective equipment use, severity of injuries, and requirement for intensive or invasive care. This study highlights the importance of vigilance and other safety behaviours when unmounted and around horses, and proposes specific targets for future injury prevention campaigns, both in setting of organised and private equestrian activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mitochondrial disorders in progressive muscular dystrophies

Directory of Open Access Journals (Sweden)

D. A. Kharlamov

2014-01-01

Full Text Available The literature review gives data on the role of mitochondrial disorders in the pathogenesis of different progressive muscular dystrophies. It describes changes in Duchenne, limb-girdle, facial scapulohumeral (Landuzi—Degerina muscular dystrophies. The review is based on both clinical and experimental animal studies. Along with the implication of mitochondria in the pathogenesis of the diseases, it describes muscular dystrophy treatment options compensating for energy disorders and overcoming oxidative stress and mitochondrial dysfunction. Mitochondrial studies in different muscle diseases hand physicians treatment modalities that fail to lead to recovery, but compensate for disorders caused by mutations in the genetic apparatus. 

A systematic review on the influence of pre-existing disability on sustaining injury.

Science.gov (United States)

Yung, A; Haagsma, J A; Polinder, S

2014-01-01

To systematically review studies measuring the influence of pre-existing disability on the risk of sustaining an injury. Systematic review. Electronic databases searched included Medline (Pubmed), ProQuest, Ovid and EMBASE. Studies (1990-2010) in international peer-reviewed journals were identified with main inclusion criteria being that the study assessed involvement of injury sustained by persons with and without pre-existing disability. Studies were collated by design and methods, and evaluation of results. Twenty-two studies met the inclusion criteria of our review. All studies found that persons with disabilities were at a significantly higher risk of sustaining injuries than those without. Persons with disability had a 30-450% increased odds (odds ratio 1.3-5.5) of sustaining injury compared to persons without disability. Among persons with pre-existing disability, the high risk groups of sustaining an injury are children and elderly. People with disabilities experience a higher risk to sustain an injury in comparison to the healthy population. There is a high need for large epidemiological studies of injury among persons with disability, to better address these unique risk profiles in order to prevent additional disability or secondary conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mitochondrial Modulation by Epigallocatechin 3-Gallate Ameliorates Cisplatin Induced Renal Injury through Decreasing Oxidative/Nitrative Stress, Inflammation and NF-kB in Mice

Science.gov (United States)

Wang, Xueping; Wang, Ping; Fu, Guanghou; Meng, Hongzhou; Wang, Yimin; Jin, Baiye

2015-01-01

Cancer chemotherapy drug cisplatin is known for its nephrotoxicity. The aim of this study is to investigate whether Epigallocatechin 3-Gallate (EGCG) can reduce cisplatin mediated side effect in kidney and to understand its mechanism of protection against tissue injury. We used a well-established 3-day cisplatin induced nephrotoxicity mice model where EGCG were administered. EGCG is a major active compound in Green Tea and have strong anti-oxidant and anti-inflammatory properties. EGCG protected against cisplatin induced renal dysfunction as measured by serum creatinine and blood urea nitrogen (BUN). EGCG improved cisplatin induced kidney structural damages such as tubular dilatation, cast formation, granulovaculoar degeneration and tubular cell necrosis as evident by PAS staining. Cisplatin induced kidney specific mitochondrial oxidative stress, impaired activities of mitochondrial electron transport chain enzyme complexes, impaired anti-oxidant defense enzyme activities such as glutathione peroxidase (GPX) and manganese superoxide dismutase (MnSOD) in mitochondria, inflammation (tumor necrosis factor α and interleukin 1β), increased accumulation of NF-κB in nuclear fraction, p53 induction, and apoptotic cell death (caspase 3 activity and DNA fragmentation). Treatment of mice with EGCG markedly attenuated cisplatin induced mitochondrial oxidative/nitrative stress, mitochondrial damages to electron transport chain activities and antioxidant defense enzyme activities in mitochondria. These mitochondrial modulations by EGCG led to protection mechanism against cisplatin induced inflammation and apoptotic cell death in mice kidney. As a result, EGCG improved renal function in cisplatin mediated kidney damage. In addition to that, EGCG attenuated cisplatin induced apoptotic cell death and mitochondrial reactive oxygen species (ROS) generation in human kidney tubular cell line HK-2. Thus, our data suggest that EGCG may represent new promising adjunct candidate for

Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein

Directory of Open Access Journals (Sweden)

Rui-Xin Yang

2017-06-01

Full Text Available Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB, against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro. SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.

Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein.

Science.gov (United States)

Yang, Rui-Xin; Lei, Jie; Wang, Bo-Dong; Feng, Da-Yun; Huang, Lu; Li, Yu-Qian; Li, Tao; Zhu, Gang; Li, Chen; Lu, Fang-Fang; Nie, Tie-Jian; Gao, Guo-Dong; Gao, Li

2017-01-01

Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R) injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB), against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro . SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.

Rethinking Heat Injury in the SOF Multipurpose Canine: A Critical Review.

Science.gov (United States)

Baker, Janice L; Hollier, Paul J; Miller, Laura; Lacy, Ward A

2012-01-01

Heat injury is a significant concern of the Special Operations Forces Multipurpose Canine (SOF MPC). The unique athletic abilities and working environment of the SOF MPC differ from that of companion dogs or even conventional military working dogs. This should be considered in the prevention, diagnosis, and treatment of heat injury of the SOF MPC. A critical review of the literature on canine heat injury as it pertains to working dogs demonstrates limited scientific evidence on best practices for immediate clinical management of heat injury in SOF MPCs. A majority of management guidelines for heat injury in veterinary reference books and journals are based on review articles or professional opinion of the author vs. evidence from original research. In addition, guidelines are written primarily for companion animal populations vs. SOF MPCs and focus on measures to be undertaken in a clinical setting vs. point of injury. The phenomenon of ?circular referencing? is also prevalent in the heat injury literature. Current guidelines supported by review articles and textbooks often provide no citation or cite other review articles for clinical standards such as normal temperature ranges, treatment methods, and recurrence of heat injury. This ?circular referencing? phenomenon misrepresents anecdotal evidence and professional opinion as scientifically validated, reinforcing concepts and recommendations that are not truly supported by the evidence. Further study is needed to fully understand heat injury in SOF MPCs and how this applies to prevention, diagnosis and treatment guidelines. In order to provide SOF canine programs with best clinical advice and care, SOF Veterinarians must make clinical judgments based on evaluation of the most accurate and valid information possible. Clinical guidelines are fluid and should be reviewed regularly for relevance to the defined population in question. Clinical Guidelines should also be utilized as guiding principles in conjunction with

Mechanisms of sports injuries among professional footballers:  a review

OpenAIRE

Ibikundle, P.O.; Ani, U.K.; Useh, U.; Akosile, C.O.

2014-01-01

Football is an impact collision sport, with injuries occurring in both contact and non-contact situations. Injuries may be caused by complex interactions between internal and external risk factors. The internal factors such as age, sex, and body compositions may influence the risk of sustaining injuries, predisposing the player to injury, and are therefore by definitions risk factors. The main purpose of this study was to review articles and draw attention to the prevalence, severity and mech...

Environmental Subconcussive Injury, Axonal Injury, and Chronic Traumatic Encephalopathy

Directory of Open Access Journals (Sweden)

Wendy A. Morley

2018-03-01

Full Text Available Brain injury occurs in two phases: the initial injury itself and a secondary cascade of precise immune-based neurochemical events. The secondary phase is typically functional in nature and characterized by delayed axonal injury with more axonal disconnections occurring than in the initial phase. Axonal injury occurs across the spectrum of disease severity, with subconcussive injury, especially when repetitive, now considered capable of producing significant neurological damage consistent with axonal injury seen in clinically evident concussion, despite no observable symptoms. This review is the first to introduce the concept of environmental subconcussive injury (ESCI and sets out how secondary brain damage from ESCI once past the juncture of microglial activation appears to follow the same neuron-damaging pathway as secondary brain damage from conventional brain injury. The immune response associated with ESCI is strikingly similar to that mounted after conventional concussion. Specifically, microglial activation is followed closely by glutamate and calcium flux, excitotoxicity, reactive oxygen species and reactive nitrogen species (RNS generation, lipid peroxidation, and mitochondrial dysfunction and energy crisis. ESCI damage also occurs in two phases, with the primary damage coming from microbiome injury (due to microbiome-altering events and secondary damage (axonal injury from progressive secondary neurochemical events. The concept of ESCI and the underlying mechanisms have profound implications for the understanding of chronic traumatic encephalopathy (CTE etiology because it has previously been suggested that repetitive axonal injury may be the primary CTE pathogenesis in susceptible individuals and it is best correlated with lifetime brain trauma load. Taken together, it appears that susceptibility to brain injury and downstream neurodegenerative diseases, such as CTE, can be conceptualized as a continuum of brain resilience. At one end

Retrospective review of lumbosacral dissociations in blast injuries.

Science.gov (United States)

Helgeson, Melvin D; Lehman, Ronald A; Cooper, Patrick; Frisch, Michael; Andersen, Romney C; Bellabarba, Carlo

2011-04-01

Retrospective review of medical records and radiographs. We assessed the clinical outcomes of lumbosacral dissociation (LSD) after traumatic, combat-related injuries, and to review our management of these distinct injuries and report our preliminary follow-up. LSD injuries are an anatomic separation of the pelvis from the spinal column, and are the result of high-energy trauma. A relative increase in these injuries has been seen in young healthy combat casualties subjected to high-energy blast trauma. We performed a retrospective review of inpatient/outpatient medical records and radiographs for all patients treated at our institution with combat-related lumbosacral dissociations. Twenty-three patients met inclusion criteria of combat-related lumbosacral dissociations with one-year follow-up. Patients were treated as follows: no fixation (9), sacroiliac screw fixation (8), posterior spinal fusion (5) and sacral plate (1). All patients with radiographic evidence of a zone III sacral fracture, in addition to associated lumbar fractures indicating loss of the iliolumbar ligamentous complex integrity were included. In 15 patients, the sacral fracture were an H or U type zone III fracture, whereas in the remaining nine, the sacral fracture was severely comminuted and unable to classify (six open fractures). There was no difference in visual analog scale (VAS) between treatment modalities. Two open injuries had residual infections. One patient treated with an L4-ilium posterior spinal fusion with instrumentation required instrumentation removal for infection. At a mean follow-up of 1.71 years (range, 1-4.5), 11 patients (48%) still reported residual pain and the mean VAS at latest follow-up was 1.7 (range, 0-7). Operative stabilization promoted healing and earlier mobilization, but carries a high-postoperative risk of infection. Nonoperative management should be considered in patients whose comorbidities prevent safe stabilization.

Road Traffic Injuries Among Iranian Children and Adolescents: An Epidemiological Review

Directory of Open Access Journals (Sweden)

Salar Behzadnia

2016-01-01

Full Text Available Context: Road traffic injuries (RTIs are the leading cause of death and globally kill 1.2 million people every year and leave 20 - 50 million people injured and disabled. In Iran, traffic related fatalities are the leading cause of death among all inadvertent fatal injuries imposed on children under five. Herein, authors review the epidemiological studies performed on vehicle accidents among Iranian children and adolescents to improve the knowledge about these preventable events. Evidence Acquisition: International databases including PubMed, Google scholar, science direct Cochrane library, and national data bases such as scientific information database (SID were searched for terms; children, motor vehicle accident, road traffic injuries, Iran 2000 - 2015. Publication in Persian or English language related to the subject including Iranian children and adolescent's age groups were included. Among the 312 articles, 11 (two abstracts and nine full texts were selected. Nine full texts were reviewed. Results: From 22865 victims, about 3578 children and adolescents under 19 years old were identified. Males were more affected than females. Pedestrian injury with 43.66% was the most common case of road traffic injuries. Head trauma was the most common cause of injuries reported by eight of the reviewed articles. Most of the accidents occurred between 1:00 - 6:00 PM. Most of RTIs occurred in summer. Care by emergency medical services (EMS (29.14% was reported by five out of the nine reviewed article. Conclusions: Most of the road traffic injuries among Iranian children and adolescents are preventable using appropriate preventive strategies such as safety facilities, safe vehicles, and safe traffic behavior, and establishing comprehensive public education programs for older children and their parents.

TRAUMATIC BRAIN INJURY CHILDREN: A LITERATURE REVIEW

Directory of Open Access Journals (Sweden)

Denismar Borges de Miranda

2013-09-01

Full Text Available Objective: to know the scientific literature on head injury in children. Method: this study is an integrative review of published articles in the database SciELO the period 2000-2010. Results: 10 articles were analyzed, from which emerged four categories: causes of traumatic brain child infant prognosis of traumatic brain child, treating children victims of child head injury and complications of therapy used for child victims of traumatic brain injury in children. Conclusions: there is consensus among the authors investigated the factors associated with better prognosis of traumatic brain child, remain vague and uncertain. They add that the success of this customer service related to the control of complications arising from cerebral trauma and mostly are treatable and / or preventable.

Neurodegenerative and Fatiguing Illnesses, Infections and Mitochondrial Dysfunction: Use of Natural Supplements to Improve Mitochondrial Function

Directory of Open Access Journals (Sweden)

Garth L. Nicolson

2014-01-01

Full Text Available Background: Many chronic diseases and illnesses are associated with one or more chronic infections, dysfunction of mitochondria and reduced production of ATP. This results in fatigue and other symptoms that occur in most if not all chronic conditions and diseases. Methods: This is a review of the published literature on chronic infections in neurodegenerative diseases and fatiguing illnesses that are also typified by mitochondrial dysfunction. This contribution also reviews the use of natural supplements to enhance mitochondrial function and reduce the effects of chronic infections to improve overall function in various chronic illnesses. Results: Mitochondrial function can be enhanced by the use of various natural supplements, notably Lipid Replacement Therapy (LRT using glyerolphospholipids and other mitochondrial supplements. In various chronic illnesses that are characterized by the presence of chronic infections, such as intracellular bacteria (Mycoplasma, Borrelia, Chlamydia and other infections and viruses, LRT has proven useful in multiple clinical trials. For example, in clinical studies on chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses where a large majority of patients have chronic infections, LRT significantly reduced fatigue by 35-43% in different clinical trials and increased mitochondrial function. In clinical trials on patients with multiple intracellular bacterial infections and intractable fatigue LRT plus other mitochondrial supplements significantly decreased fatigue and improved mood and cognition. Conclusions: LRT formulations designed to improve mitochondrial function appear to be useful as non-toxic dietary supplements for reducing fatigue and restoring mitochondrial and other cellular membrane functions in patients with chronic illnesses and multiple chronic infections.

Sirtuin 1 Agonist Minimizes Injury and Improves the Immune Response Following Traumatic Shock.

Science.gov (United States)

Luciano, Jason A; Kautza, Benjamin; Darwiche, Sophie; Martinez, Silvia; Stratimirovic, Sladjana; Waltz, Paul; Sperry, Jason; Rosengart, Matthew; Shiva, Sruti; Zuckerbraun, Brian S

2015-08-01

Survival from traumatic injury requires a coordinated and controlled inflammatory and immune response. Mitochondrial and metabolic responses to stress have been shown to play a role in these inflammatory and immune responses. We hypothesized that increases in mitochondrial biogenesis via a sirtuin 1 agonist would decrease tissue injury and partially ameliorate the immunosuppression seen following trauma. C57Bl/6 mice were subjected to a multiple trauma model. Mice were pretreated with either 100 mg/kg per day of the sirtuin 1 agonist, Srt1720, via oral gavage for 2 days prior to trauma and extended until the day the animals were killed, or they were pretreated with peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) siRNA via hydrodynamic tail vein injection 48 h prior to trauma. Markers for mitochondrial function and biogenesis were measured in addition to splenocyte proliferative capacity and bacterial clearance. Srt1720 was noted to improve mitochondrial biogenesis, mitochondrial function, and complex IV activity following traumatic injury (P hepatic injury with significant reductions in serum alanine aminotransferase levels seen in mice treated with srt1720. Splenocyte proliferative capacity and intraperitoneal bacterial clearance were evaluated as markers for overall immune function following trauma-hemorrhage. Treatment with Srt1720 minimized the trauma-induced decreases in splenocyte proliferation (P clearance. The PGC1α signaling pathway is an important regulator of mitochondrial function and biogenesis, which can potentially be harnessed to protect against hepatic injury and minimize the immunosuppression that is seen following trauma-hemorrhage.

DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice.

Science.gov (United States)

Mayurasakorn, Korapat; Niatsetskaya, Zoya V; Sosunov, Sergey A; Williams, Jill J; Zirpoli, Hylde; Vlasakov, Iliyan; Deckelbaum, Richard J; Ten, Vadim S

2016-01-01

Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury. 10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4-5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8-9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS) and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA. Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia. Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA.

DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice.

Directory of Open Access Journals (Sweden)

Korapat Mayurasakorn

Full Text Available Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA protected neonatal mice against hypoxia-ischemia (HI brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury.10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4-5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8-9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA.Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia.Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA.

Guarding the Precious Smile: Incidence and Prevention of Injury in Sports: A Review

OpenAIRE

Dhillon, Bikramjit Singh; Sood, Nikhil; Sood, Niti; Sah, Nupur; Arora, Dhruv; Mahendra, Ashish

2014-01-01

The paper provides a review about the orofacial injuries sustained during sports and the options available to the athletes for their prevention. It was done with a purpose to determine three different aspects incidence of dental injury during sporting activities, role of mouthguards in preventing sports injury, types of mouthguards and their properties. From this review, it is clear that sports carry a considerable risk of injury, this is not only true for the contact sports such as rugby or ...

ALDH2 restores exhaustive exercise-induced mitochondrial dysfunction in skeletal muscle

International Nuclear Information System (INIS)

Zhang, Qiuping; Zheng, Jianheng; Qiu, Jun; Wu, Xiahong; Xu, Yangshuo; Shen, Weili; Sun, Mengwei

2017-01-01

Background: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is highly expressed in heart and skeletal muscles, and is the major enzyme that metabolizes acetaldehyde and toxic aldehydes. The cardioprotective effects of ALDH2 during cardiac ischemia/reperfusion injury have been recognized. However, less is known about the function of ALDH2 in skeletal muscle. This study was designed to evaluate the effect of ALDH2 on exhaustive exercise-induced skeletal muscle injury. Methods: We created transgenic mice expressing ALDH2 in skeletal muscles. Male wild-type C57/BL6 (WT) and ALDH2 transgenic mice (ALDH2-Tg), 8-weeks old, were challenged with exhaustive exercise for 1 week to induce skeletal muscle injury. Animals were sacrificed 24 h post-exercise and muscle tissue was excised. Results: ALDH2-Tg mice displayed significantly increased treadmill exercise capacity compared to WT mice. Exhaustive exercise caused an increase in mRNA levels of the muscle atrophy markers, Atrogin-1 and MuRF1, and reduced mitochondrial biogenesis and fusion in WT skeletal muscles; these effects were attenuated in ALDH2-Tg mice. Exhaustive exercise also enhanced mitochondrial autophagy pathway activity, including increased conversion of LC3-I to LC3-II and greater expression of Beclin1 and Bnip3; the effects of which were mitigated by ALDH2 overexpression. In addition, ALDH2-Tg reversed the increase of an oxidative stress biomarker (4-hydroxynonenal) and decreased levels of mitochondrial antioxidant proteins, including manganese superoxide dismutase and NAD(P)H:quinone oxidoreductase 1, in skeletal muscle induced by exhaustive exercise. Conclusion: ALDH2 may reverse skeletal muscle mitochondrial dysfunction due to exhaustive exercise by regulating mitochondria dynamic remodeling and enhancing the quality of mitochondria. - Highlights: • Skeletal muscle ALDH2 expression and activity declines during exhaustive exercise. • ALDH2 overexpression enhances physical performance and restores muscle

Genetics of mitochondrial dysfunction and infertility.

Science.gov (United States)

Demain, L A M; Conway, G S; Newman, W G

2017-02-01

Increasingly, mitochondria are being recognized as having an important role in fertility. Indeed in assisted reproductive technologies mitochondrial function is a key indicator of sperm and oocyte quality. Here, we review the literature regarding mitochondrial genetics and infertility. In many multisystem disorders caused by mitochondrial dysfunction death occurs prior to sexual maturity, or the clinical features are so severe that infertility may be underreported. Interestingly, many of the genes linked to mitochondrial dysfunction and infertility have roles in the maintenance of mitochondrial DNA or in mitochondrial translation. Studies on populations with genetically uncharacterized infertility have highlighted an association with mitochondrial DNA deletions, whether this is causative or indicative of poor functioning mitochondria requires further examination. Studies on the impact of mitochondrial DNA variants present conflicting data but highlight POLG as a particularly interesting candidate gene for both male and female infertility. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Head injury predictors in sports trauma--a state-of-the-art review.

Science.gov (United States)

Fernandes, Fábio A O; de Sousa, Ricardo J Alves

2015-08-01

Head injuries occur in a great variety of sports. Many of these have been associated with neurological injuries, affecting the central nervous system. Some examples are motorsports, cycling, skiing, horse riding, mountaineering and most contact sports such as football, ice and field hockey, soccer, lacrosse, etc. The outcome of head impacts in these sports can be very severe. The worst-case scenarios of permanent disability or even death are possibilities. Over recent decades, many In recent decades, a great number of head injury criteria and respective thresholds have been proposed. However, the available information is much dispersed and a consensus has still not been achieved regarding the best injury criteria or even their thresholds. This review paper gives a thorough overview of the work carried out by the scientific community in the field of impact biomechanics about head injuries sustained during sports activity. The main goal is to review the head injury criteria, as well as their thresholds. Several are reviewed, from the predictors based on kinematics to the ones based on human tissue thresholds. In this work, we start to briefly introduce the head injuries and their mechanisms commonly seen as a result of head trauma in sports. Then, we present and summarize the head injury criteria and their respective thresholds. © IMechE 2015.

Work injury management model and implication in Hong Kong: a literature review.

Science.gov (United States)

Chong, Cecilia Suk-Mei; Cheng, Andy Shu-Kei

2010-01-01

The objective of this review is to explore the work injury management models in literatures and the essential components in different models. The resulting information could be used to develop an integrated holistic model that could be applied in the work injury management system in Hong Kong. A keyword search of MEDLINE and CINAHL databases was conducted. A total of 68 studies related to the management of an injury were found within the above mentioned electronic database. Together with the citation tracking, there were 13 studies left for selection after the exclusion screening. Only 7 out of those 13 studies met the inclusion criteria for review. It is noticeable that the most important component in the injury management model in the reviewed literatures is early intervention. Because of limitations in Employees' Compensation Ordinance in Hong Kong, there is an impetus to have a model and practice guideline for work injury management in Hong Kong to ensure the quality of injury management services. At the end of this paper, the authors propose a work injury management model based on the employees' compensation system in Hong Kong. This model can be used as a reference for those countries adopting similar legislation as in Hong Kong.

Equestrian sport-related injuries: a review of current literature.

Science.gov (United States)

Havlik, Heather S

2010-01-01

Equestrian sports continue to grow in popularity in the Unites States and abroad, with an estimated 30 million people riding horses annually in the United States alone. Approximately one in five of these riders will suffer a serious injury during their riding career, requiring medical care and potentially hospitalization. Riding carries with it an implicit risk of injury associated with the unpredictability of the animals, the rider's head being positioned approximately 9 feet off the ground, and traveling unrestrained at speeds up to 40 mph. This article reviews common equestrian injuries, epidemiology, mechanism of injury, risk factors, and prevention strategies, with an emphasis on the more dangerous aspects of the sport.

Advances in the understanding of mitochondrial DNA as a pathogenic factor in inflammatory diseases [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Ray K. Boyapati

2017-02-01

Full Text Available Mitochondrial DNA (mtDNA has many similarities with bacterial DNA because of their shared common ancestry. Increasing evidence demonstrates mtDNA to be a potent danger signal that is recognised by the innate immune system and can directly modulate the inflammatory response. In humans, elevated circulating mtDNA is found in conditions with significant tissue injury such as trauma and sepsis and increasingly in chronic organ-specific and systemic illnesses such as steatohepatitis and systemic lupus erythematosus. In this review, we examine our current understanding of mtDNA-mediated inflammation and how the mechanisms regulating mitochondrial homeostasis and mtDNA release represent exciting and previously under-recognised important factors in many human inflammatory diseases, offering many new translational opportunities.

Universal Motorcycle Helmet Laws to Reduce Injuries: A Community Guide Systematic Review.

Science.gov (United States)

Peng, Yinan; Vaidya, Namita; Finnie, Ramona; Reynolds, Jeffrey; Dumitru, Cristian; Njie, Gibril; Elder, Randy; Ivers, Rebecca; Sakashita, Chika; Shults, Ruth A; Sleet, David A; Compton, Richard P

2017-06-01

Motorcycle crashes account for a disproportionate number of motor vehicle deaths and injuries in the U.S. Motorcycle helmet use can lead to an estimated 42% reduction in risk for fatal injuries and a 69% reduction in risk for head injuries. However, helmet use in the U.S. has been declining and was at 60% in 2013. The current review examines the effectiveness of motorcycle helmet laws in increasing helmet use and reducing motorcycle-related deaths and injuries. Databases relevant to health or transportation were searched from database inception to August 2012. Reference lists of reviews, reports, and gray literature were also searched. Analysis of the data was completed in 2014. A total of 60 U.S. studies qualified for inclusion in the review. Implementing universal helmet laws increased helmet use (median, 47 percentage points); reduced total deaths (median, -32%) and deaths per registered motorcycle (median, -29%); and reduced total injuries (median, -32%) and injuries per registered motorcycle (median, -24%). Repealing universal helmet laws decreased helmet use (median, -39 percentage points); increased total deaths (median, 42%) and deaths per registered motorcycle (median, 24%); and increased total injuries (median, 41%) and injuries per registered motorcycle (median, 8%). Universal helmet laws are effective in increasing motorcycle helmet use and reducing deaths and injuries. These laws are effective for motorcyclists of all ages, including younger operators and passengers who would have already been covered by partial helmet laws. Repealing universal helmet laws decreased helmet use and increased deaths and injuries. Published by Elsevier Inc.

A Review of a Decade of Rugby Union Injury Epidemiology: 2007-2017.

Science.gov (United States)

Viviers, Pierre L; Viljoen, Jeandré T; Derman, Wayne

Rugby union is the most widely played team collision sport globally. As with other contact sports, there is substantial risk of injury. To date, the majority of studies on injury epidemiology have focused on elite male cohorts, which inherently prevents extrapolation of research findings to other groups within the player continuum. This review aims to describe emerging injury trends across the spectrum of various rugby union subpopulations and to highlight gaps that may influence future injury prevention tactics. Relevant articles published from 2007 to 2017 were obtained by searching MEDLINE, PubMed, and SPORT Discus. Studies on 15-a-side rugby union, implemented according to the 2007 consensus statement on injury definitions and data collection procedures for injuries in rugby union, were used. Clinical review. Level 3. Match injuries occur more frequently than training injuries. Injury rates increase consistently according to age and level of play. Severity of injury often is greater among lower levels of the game, and sex-specific differences relating to injury patterns and incidence rates exist. To date, a paucity of injury surveillance data exists for women and players of both sexes at all levels of community rugby union. Furthermore, the incidence of injuries and illnesses are poorly reported in epidemiological studies. Despite methodological differences, injury trends remain consistent throughout all levels of play.

CHRISTMAS 2014 : GOING TO EXTREMES Nintendo related injuries and other problems: review

NARCIS (Netherlands)

Jalink, Maarten B.; Heineman, Erik; Pierie, Jean-Pierre E. N.; Hoedemaker, Henk O. ten Cate

2014-01-01

Objective To identify all reported cases of injury and other problems caused by using a Nintendo video gaming system. Design Review. Data sources and review methods Search of PubMed and Embase in June 2014 for reports on injuries and other problems caused by using a Nintendo gaming system. Results

Mitochondrial DNA Unwinding Enzyme Required for Liver Regeneration | Center for Cancer Research

Science.gov (United States)

The liver has an exceptional capacity to proliferate. This ability allows the liver to regenerate its mass after partial surgical removal or injury and is the key to successful partial liver transplants. Liver cells, called hepatocytes, are packed with mitochondria, and regulating mitochondrial DNA (mtDNA) copy number is crucial to mitochondrial function, including energy production, during proliferation. Yves Pommier, M.D., Ph.D., of CCR’s Developmental Therapeutics Branch, and his colleagues recently showed that the vertebrate mitochondrial topoisomerase, Top1mt, was critical in maintaining mitochondrial function in the heart after doxorubicin-induced damage. The group wondered whether Top1mt might play a similar role in liver regeneration.

Mitochondrial dysfunction and organophosphorus compounds

Energy Technology Data Exchange (ETDEWEB)

Karami-Mohajeri, Somayyeh [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Kerman University of Medical Sciences, Kerman (Iran, Islamic Republic of); Abdollahi, Mohammad, E-mail: Mohammad.Abdollahi@UToronto.Ca [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2013-07-01

Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP.

Mitochondrial dysfunction and organophosphorus compounds

International Nuclear Information System (INIS)

Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

2013-01-01

Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP

Mitochondrial pharmacology: electron transport chain bypass as strategies to treat mitochondrial dysfunction.

Science.gov (United States)

Atamna, Hani; Mackey, Jeanette; Dhahbi, Joseph M

2012-01-01

Mitochondrial dysfunction (primary or secondary) is detrimental to intermediary metabolism. Therapeutic strategies to treat/prevent mitochondrial dysfunction could be valuable for managing metabolic and age-related disorders. Here, we review strategies proposed to treat mitochondrial impairment. We then concentrate on redox-active agents, with mild-redox potential, who shuttle electrons among specific cytosolic or mitochondrial redox-centers. We propose that specific redox agents with mild redox potential (-0.1 V; 0.1 V) improve mitochondrial function because they can readily donate or accept electrons in biological systems, thus they enhance metabolic activity and prevent reactive oxygen species (ROS) production. These agents are likely to lack toxic effects because they lack the risk of inhibiting electron transfer in redox centers. This is different from redox agents with strong negative (-0.4 V; -0.2 V) or positive (0.2 V; 0.4 V) redox potentials who alter the redox status of redox-centers (i.e., become permanently reduced or oxidized). This view has been demonstrated by testing the effect of several redox active agents on cellular senescence. Methylene blue (MB, redox potential ≅10 mV) appears to readily cycle between the oxidized and reduced forms using specific mitochondrial and cytosolic redox centers. MB is most effective in delaying cell senescence and enhancing mitochondrial function in vivo and in vitro. Mild-redox agents can alter the biochemical activity of specific mitochondrial components, which then in response alters the expression of nuclear and mitochondrial genes. We present the concept of mitochondrial electron-carrier bypass as a potential result of mild-redox agents, a method to prevent ROS production, improve mitochondrial function, and delay cellular aging. Thus, mild-redox agents may prevent/delay mitochondria-driven disorders. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Injury and biomechanical perspectives on the rugby scrum: a review of the literature.

Science.gov (United States)

Trewartha, Grant; Preatoni, Ezio; England, Michael E; Stokes, Keith A

2015-04-01

As a collision sport, rugby union has a relatively high overall injury incidence, with most injuries being associated with contact events. Historically, the set scrum has been a focus of the sports medicine community due to the perceived risk of catastrophic spinal injury during scrummaging. The contemporary rugby union scrum is a highly dynamic activity but to this point has not been well characterised mechanically. In this review, we synthesise the available research literature relating to the medical and biomechanical aspects of the rugby union scrum, in order to (1) review the injury epidemiology of rugby scrummaging; (2) consider the evidence for specific injury mechanisms existing to cause serious scrum injuries and (3) synthesise the information available on the biomechanics of scrummaging, primarily with respect to force production. The review highlights that the incidence of acute injury associated with scrummaging is moderate but the risk per event is high. The review also suggests an emerging acknowledgement of the potential for scrummaging to lead to premature chronic degeneration injuries of the cervical spine and summarises the mechanisms by which these chronic injuries are thought to occur. More recent biomechanical studies of rugby scrummaging confirm that scrum engagement forces are high and multiplanar, but can be altered through modifications to the scrum engagement process which control the engagement velocity. As the set scrum is a relatively 'controlled' contact situation within rugby union, it remains an important area for intervention with a long-term goal of injury reduction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Urinary Tract Injury in Gynecologic Laparoscopy for Benign Indication: A Systematic Review.

Science.gov (United States)

Wong, Jacqueline M K; Bortoletto, Pietro; Tolentino, Jocelyn; Jung, Michael J; Milad, Magdy P

2018-01-01

To perform a comprehensive literature review of the incidence, location, etiology, timing, management, and long-term sequelae of urinary tract injury in gynecologic laparoscopy for benign indication. A systematic review of PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov was conducted. Four hundred thirty-three studies were screened for inclusion with 136 full-text articles reviewed. Ninety studies published between 1975 and 2015 met inclusion criteria, representing 140,444 surgeries. Articles reporting the incidence of urinary tract injury in gynecologic laparoscopy for benign indication were included. Exclusion criteria comprised malignancy, surgery by urogynecologists, research not in English, and insufficient data. A total of 458 lower urinary tract injuries were reported with an incidence of 0.33% (95% CI 0.30-0.36). Bladder injury (0.24%, 95% CI 0.22-0.27) was overall three times more frequent than ureteral injury (0.08%, 95% CI 0.07-0.10). Laparoscopic hysterectomy not otherwise specified (1.8%, 95% CI 1.2-2.6) and laparoscopically assisted vaginal hysterectomy (1.0%, 95% CI 0.9-1.2) had the highest rates of injury. Most ureteral injuries resulted from electrosurgery (33.3%, 95% CI 24.3-45.8), whereas most bladder injuries resulted from lysis of adhesions (23.3%, 95% CI 18.7-29.0). Ureteral injuries were most often recognized postoperatively (60%, 95% CI 47-76) and were repaired by open ureteral anastomosis (47.4%, 95% CI 36.3-61.9). In contrast, bladder injuries were most often recognized intraoperatively (85%, 95% CI 75-95) and were repaired by laparoscopic suturing (34.9%, 95% CI 29.2-41.7). The incidence of lower urinary tract injury in gynecologic laparoscopy for benign indication remains low at 0.33%. Bladder injury was three times more common than ureteral injury, although ureteral injuries were more often unrecognized intraoperatively and underwent open surgical repair. These risk estimates can assist gynecologic surgeons in effectively

Flurbiprofen, a Cyclooxygenase Inhibitor, Protects Mice from Hepatic Ischemia/Reperfusion Injury by Inhibiting GSK-3β Signaling and Mitochondrial Permeability Transition

Science.gov (United States)

Fu, Hailong; Chen, Huan; Wang, Chengcai; Xu, Haitao; Liu, Fang; Guo, Meng; Wang, Quanxing; Shi, Xueyin

2012-01-01

Flurbiprofen acts as a nonselective inhibitor for cyclooxygenases (COX-1 and COX-2), but its impact on hepatic ischemia/reperfusion (I/R) injury remains unclear. Mice were randomized into sham, I/R and flurbiprofen (Flurb) groups. The hepatic artery and portal vein to the left and median liver lobes were occluded for 90 min and unclamped for reperfusion to establish a model of segmental (70%) warm hepatic ischemia. Pretreatment of animals with flurbiprofen prior to I/R insult significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), and prevented hepatocytes from I/R-induced apoptosis/necrosis. Moreover, flurbiprofen dramatically inhibited mitochondrial permeability transition (MPT) pore opening, and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that flurbiprofen markedly inhibited glycogen synthase kinase (GSK)-3β activity and increased phosphorylation of GSK-3β at Ser9, which, consequently, could modulate the adenine nucleotide translocase (ANT)–cyclophilin D (CyP-D) complex and the susceptibility to MPT induction. Therefore, administration of flurbiprofen prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through inhibition of MPT and inactivation of GSK-3β, and provides experimental evidence for clinical use of flurbiprofen to protect liver function in surgical settings in addition to its conventional use for pain relief. PMID:22714712

KB-R7943, a plasma membrane Na(+)/Ca(2+) exchanger inhibitor, blocks opening of the mitochondrial permeability transition pore.

Science.gov (United States)

Wiczer, Brian M; Marcu, Raluca; Hawkins, Brian J

2014-01-31

The isothiourea derivative, KB-R7943, inhibits the reverse-mode of the plasma membrane sodium/calcium exchanger and protects against ischemia/reperfusion injury. The mechanism through which KB-R7943 confers protection, however, remains controversial. Recently, KB-R7943 has been shown to inhibit mitochondrial calcium uptake and matrix overload, which may contribute to its protective effects. While using KB-R7943 for this purpose, we find here no evidence that KB-R7943 directly blocks mitochondrial calcium uptake. Rather, we find that KB-R7943 inhibits opening of the mitochondrial permeability transition pore in permeabilized cells and isolated liver mitochondria. Furthermore, we find that this observation correlates with protection against calcium ionophore-induced mitochondrial membrane potential depolarization and cell death, without detrimental effects to basal mitochondrial membrane potential or complex I-dependent mitochondrial respiration. Our data reveal another mechanism through which KB-R7943 may protect against calcium-induced injury, as well as a novel means to inhibit the mitochondrial permeability transition pore. Copyright © 2014 Elsevier Inc. All rights reserved.

Distal triceps injuries (including snapping triceps): A systematic review of the literature.

Science.gov (United States)

Shuttlewood, Kimberley; Beazley, James; Smith, Christopher D

2017-06-18

To review current literature on types of distal triceps injury and determine diagnosis and appropriate management. We performed a systematic review in PubMed, Cochrane and EMBASE using the terms distal triceps tears and snapping triceps on the 10 th January 2017. We excluded all animal, review, foreign language and repeat papers. We reviewed all papers for relevance and of the papers left we were able to establish the types of distal triceps injury, how these injuries are diagnosed and investigated and the types of management of these injuries including surgical. The results are then presented in a review paper format. Three hundred and seventy-nine papers were identified of which 65 were relevant to distal triceps injuries. After exclusion we had 47 appropriate papers. The papers highlighted 2 main distal triceps injuries: Distal triceps tears and snapping triceps. Triceps tear are more common in males than females occurring in the 4 th -5 th decade of life and often due to a direct trauma but are also strongly associated with weightlifting and American football. The tears are diagnosed by history and clinically with a palpable gap. Diagnosis can be confirmed with the use of ultrasound (US) and magnetic resonance imaging. Treatment depends on type of tear. Partial tears can be treated conservatively with bracing and physio whereas acute tears need repair either open or arthroscopic using suture anchor or bone tunnel techniques with similar success. Chronic tears often need augmenting with tendon allograft or autograft. Snapping triceps are also seen more in men than women but at a mean age of 32 years. They are characterized by a snapping sensation mostly medially and can be associated with ulna nerve subluxation and ulna nerve symptoms. US is the diagnostic modality of choice due to its dynamic nature and to differentiate between snapping triceps tendon or ulna nerve. Treatment is conservative initially with activity avoidance and if that fails surgical

DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice

Science.gov (United States)

Sosunov, Sergey A.; Williams, Jill J.; Zirpoli, Hylde; Vlasakov, Iliyan; Deckelbaum, Richard J.; Ten, Vadim S.

2016-01-01

Background and Purpose Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury. Methods 10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4–5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8–9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS) and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA. Results Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia. Conclusions Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA. PMID:27513579

Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore

Energy Technology Data Exchange (ETDEWEB)

Gharanei, M.; Hussain, A. [Department of Biomolecular and Sport Sciences, Coventry University, Cox Street, Coventry, CV1 5FB (United Kingdom); Janneh, O. [Department of Biomolecular and Sport Sciences, Coventry University, Cox Street, Coventry, CV1 5FB (United Kingdom); Pharmacology Research Laboratories, 70, Pembroke Place, The University of Liverpool, Liverpool. L69 3GF (United Kingdom); Maddock, H.L., E-mail: h.maddock@coventry.ac.uk [Department of Biomolecular and Sport Sciences, Coventry University, Cox Street, Coventry, CV1 5FB (United Kingdom)

2013-04-15

Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1 μM) ± cyclosporine A (CsA, 0.2 μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin. - Highlights: ► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser

Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore

International Nuclear Information System (INIS)

Gharanei, M.; Hussain, A.; Janneh, O.; Maddock, H.L.

2013-01-01

Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1 μM) ± cyclosporine A (CsA, 0.2 μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin. - Highlights: ► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser

The association between adverse childhood experiences and adult traumatic brain injury/concussion: a scoping review.

Science.gov (United States)

Ma, Zechen; Bayley, Mark T; Perrier, Laure; Dhir, Priya; Dépatie, Lana; Comper, Paul; Ruttan, Lesley; Lay, Christine; Munce, Sarah E P

2018-01-12

Adverse childhood experiences are significant risk factors for physical and mental illnesses in adulthood. Traumatic brain injury/concussion is a challenging condition where pre-injury factors may affect recovery. The association between childhood adversity and traumatic brain injury/concussion has not been previously reviewed. The research question addressed is: What is known from the existing literature about the association between adverse childhood experiences and traumatic brain injury/concussion in adults? All original studies of any type published in English since 2007 on adverse childhood experiences and traumatic brain injury/concussion outcomes were included. The literature search was conducted in multiple electronic databases. Arksey and O'Malley and Levac et al.'s scoping review frameworks were used. Two reviewers independently completed screening and data abstraction. The review yielded six observational studies. Included studies were limited to incarcerated or homeless samples, and individuals at high-risk of or with mental illnesses. Across studies, methods for childhood adversity and traumatic brain injury/concussion assessment were heterogeneous. A positive association between adverse childhood experiences and traumatic brain injury occurrence was identified. The review highlights the importance of screening and treatment of adverse childhood experiences. Future research should extend to the general population and implications on injury recovery. Implications for rehabilitation Exposure to adverse childhood experiences is associated with increased risk of traumatic brain injury. Specific types of adverse childhood experiences associated with risk of traumatic brain injury include childhood physical abuse, psychological abuse, household member incarceration, and household member drug abuse. Clinicians and researchers should inquire about adverse childhood experiences in all people with traumatic brain injury as pre-injury health conditions can

Mitochondrial Stress Signaling Promotes Cellular Adaptations

Directory of Open Access Journals (Sweden)

Jayne Alexandra Barbour

2014-01-01

Full Text Available Mitochondrial dysfunction has been implicated in the aetiology of many complex diseases, as well as the ageing process. Much of the research on mitochondrial dysfunction has focused on how mitochondrial damage may potentiate pathological phenotypes. The purpose of this review is to draw attention to the less well-studied mechanisms by which the cell adapts to mitochondrial perturbations. This involves communication of stress to the cell and successful induction of quality control responses, which include mitophagy, unfolded protein response, upregulation of antioxidant and DNA repair enzymes, morphological changes, and if all else fails apoptosis. The mitochondrion is an inherently stressful environment and we speculate that dysregulation of stress signaling or an inability to switch on these adaptations during times of mitochondrial stress may underpin mitochondrial dysfunction and hence amount to pathological states over time.

Descriptors used to define running-related musculoskeletal injury: a systematic review.

Science.gov (United States)

Yamato, Tiê Parma; Saragiotto, Bruno Tirotti; Hespanhol Junior, Luiz Carlos; Yeung, Simon S; Lopes, Alexandre Dias

2015-05-01

Systematic review. To systematically review the descriptors used to define running-related musculoskeletal injury and to analyze the implications of different definitions on the results of studies. Studies have developed their own definitions of running-related musculoskeletal injuries based on different criteria. This may affect the rates of injury, which can be overestimated or underestimated due to the lack of a standard definition. Searches were conducted in the Embase, PubMed, CINAHL, SPORTDiscus, LILACS, and SciELO databases, without limits on date of publication and language. Only articles that reported a definition of running-related injury were included. The definitions were classified according to 3 domains and subcategories: (1) presence of physical complaint (symptom, body system involved, region), (2) interruption of training or competition (primary sports involved, extent of injury, extent of limitation, interruption, period of injury), and (3) need for medical assistance. Spearman rank correlation was performed to evaluate the correlation between the completeness of definitions and the rates of injury reported in the studies. A total of 48 articles were included. Most studies described more than half of the subcategories, but with no standardization between the terms used within each category, showing that there is no consensus for a definition. The injury rates ranged between 3% and 85%, and tended to increase with less specific definitions. The descriptors commonly used by researchers to define a running-related injury vary between studies and may affect the rates of injuries. The lack of a standardized definition hinders comparison between studies and rates of injuries.

Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

International Nuclear Information System (INIS)

Kim, Jinna; Lee, Seung-Koo; Kim, Dong Ik; Kim, Eung Yeop; Lee, Young-Mock; Lee, Joon Soo; Kim, Heung Dong

2008-01-01

Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)

Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

Energy Technology Data Exchange (ETDEWEB)

Kim, Jinna; Lee, Seung-Koo; Kim, Dong Ik [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea); Kim, Eung Yeop [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Brain Korea 21 Project for Medical Science, Seoul (Korea); Lee, Young-Mock; Lee, Joon Soo [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Kim, Heung Dong [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Yonsei University College of Medicine, Department of Pediatrics, Seoul (Korea)

2008-08-15

Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)

Systematic review of injuries in mixed martial arts.

Science.gov (United States)

Thomas, Roger E; Thomas, Bennett C

2018-01-25

To assess injury rates in all mixed martial arts (MMA) studies. Six online databases were searched until November 2017 including MEDLINE, EMBASE, CINAHL, Web of Science, PubMed, Google/Google Scholar and conference proceedings. All included studies were entered in Pub Med Single Citation Matcher and all citation chains followed. Abstracts and titles were assessed for relevance, data independently abstracted and risk of bias for all competition studies evaluated independently by two reviewers. There are data for 5,374 male and 108 female MMA fighters. For 2407 males the weighted average injury rate/1000Athletic Encounters (AE) was 246.4 and for one study of 108 females 101.9. One study provided data by professional status: professionals 135.5/1000AE and amateurs 71.0/1000AE. Reasons for stopping matches were knockout/technical knockout 173.9/1000AE for males and 175.9/1000AE for females, submission 228.6/1000AE, and referee's decision 98.2/1000AE. Losers can experience large amounts of trauma especially head trauma as matches terminate. Two studies of competitions provided personally conducted ringside assessments and both pre- and post-match examination results. The other studies reported retrospective assessments of fight records or videos or videos and scorecards. There are no studies of training injuries of professionals or injuries of amateurs or long-term follow-up of musculoskeletal injuries or neurological damage. Studies are limited to the US and Canada. There are no systematic reviews of newspaper or media accounts of fights to assess rates and numbers of injuries or mortality. The few published surveys and case reports markedly understate the worldwide situation. There are high rates of trauma in MMA. The authorities who regulate MMA and referees and physicians who monitor MMA fighters have an inadequate database to guide their work. Researchers need to adopt the same set of complete definitions of all possible injuries and measure the high and early rate

Targeting Glial Mitochondrial Function for Protection from Cerebral Ischemia: Relevance, Mechanisms, and the Role of MicroRNAs

Directory of Open Access Journals (Sweden)

Le Li

2016-01-01

Full Text Available Astrocytes and microglia play crucial roles in the response to cerebral ischemia and are effective targets for stroke therapy in animal models. MicroRNAs (miRs are important posttranscriptional regulators of gene expression that function by inhibiting the translation of select target genes. In astrocytes, miR expression patterns regulate mitochondrial function in response to oxidative stress via targeting of Bcl2 and heat shock protein 70 family members. Mitochondria play an active role in microglial activation, and miRs regulate the microglial neuroinflammatory response. As endogenous miR expression patterns can be altered with exogenous mimics and inhibitors, miR-targeted therapies represent a viable intervention to optimize glial mitochondrial function and improve clinical outcome following cerebral ischemia. In the present article, we review the role that astrocytes and microglia play in neuronal function and fate following ischemic stress, discuss the relevance of mitochondria in the glial response to injury, and present current evidence implicating miRs as critical regulators in the glial mitochondrial response to cerebral ischemia.

The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies

Directory of Open Access Journals (Sweden)

Danina M. Muntean

2016-01-01

Full Text Available Ischaemia/reperfusion (I/R injury of the heart represents a major health burden mainly associated with acute coronary syndromes. While timely coronary reperfusion has become the established routine therapy in patients with ST-elevation myocardial infarction, the restoration of blood flow into the previously ischaemic area is always accompanied by myocardial injury. The central mechanism involved in this phenomenon is represented by the excessive generation of reactive oxygen species (ROS. Besides their harmful role when highly generated during early reperfusion, minimal ROS formation during ischaemia and/or at reperfusion is critical for the redox signaling of cardioprotection. In the past decades, mitochondria have emerged as the major source of ROS as well as a critical target for cardioprotective strategies at reperfusion. Mitochondria dysfunction associated with I/R myocardial injury is further described and ultimately analyzed with respect to its role as source of both deleterious and beneficial ROS. Furthermore, the contribution of ROS in the highly investigated field of conditioning strategies is analyzed. In the end, the vascular sources of mitochondria-derived ROS are briefly reviewed.

Multifunctional Mitochondrial AAA Proteases.

Science.gov (United States)

Glynn, Steven E

2017-01-01

Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle.

Mitochondrial Causes of Epilepsy: Evaluation, Diagnosis, and Treatment.

Science.gov (United States)

Steele, Hannah E; Chinnery, Patrick F

2015-06-01

Mitochondrial disorders are frequently associated with seizures. In this review, the authors discuss the seizure patterns and distinguishing features of mitochondrial epilepsy, alongside the indications for investigating, and how to investigate epilepsy from a mitochondrial perspective. Finally, they discuss management strategies for this complex group of patients. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Perioperative Care for Pediatric Patients With Penetrating Brain Injury: A Review.

Science.gov (United States)

Mikhael, Marco; Frost, Elizabeth; Cristancho, Maria

2017-05-19

Traumatic brain injury (TBI) continues to be the leading cause of death and acquired disability in young children and adolescents, due to blunt or penetrating trauma, the latter being less common but more lethal. Penetrating brain injury (PBI) has not been studied extensively, mainly reported as case reports or case series, due to the assumption that both types of brain injury have common pathophysiology and consequently common management. However, recommendations and guidelines for the management of PBI differ from those of blunt TBI in regards to neuroimaging, intracranial pressure (ICP) monitoring, and surgical management including those pertaining to vascular injury. PBI was one of the exclusion criteria in the second edition of guidelines for the acute medical management of severe TBI in infants, children, and adolescents that was published in 2012 (it is referred to as "pediatric guidelines" in this review). Many reviews of TBI do not differentiate between the mechanisms of injury. We present an overview of PBI, its presenting features, epidemiology, and causes as well as an analysis of case series and the conclusions that may be drawn from those and other studies. More clinical trials specific to penetrating head injuries in children, focusing mainly on pathophysiology and management, are needed. The term PBI is specific to penetrating injury only, whereas TBI, a more inclusive term, describes mainly, but not only, blunt injury.

Mitochondrial Diseases: Clinical Features- Management of Patients

Directory of Open Access Journals (Sweden)

Filiz Koc

2003-02-01

Full Text Available Mitochondria are unique organells which their own DNA in cells. Human mitochondrial DNA is circular, double-stranded molecule and small. Because all mitochondria are contributed by the ovum during the formation of the zygote, the mitochondrial genom is transmitted by maternal inheritance. Multisystem disorders such as deafness, cardiomyopathy, miyopathy can be seen in mitochondrial diseases. [Archives Medical Review Journal 2003; 12(0.100: 14-31

Lawn mower injuries to the lower extremity: a 10-year retrospective review.

Science.gov (United States)

Greenhagen, Robert M; Raspovic, Katherine M; Crim, Brandon E; Ryan, Michael T; Gruen, Gary G

2013-04-01

Lawn mower injuries occur frequently in the United States and oftentimes result in extensive trauma to the lower extremities. These injuries can be quite devastating and cause there to be loss of function and amputation. The purpose of this study was to determine if there are specific factors that would help determine the best treatment protocol, patient outcomes, and prognosis after lawn mower injury to the foot and ankle. A retrospective review of medical records was performed on all patients treated at a university level 1 trauma center from 2000 to 2010. Only subjects 18 years or older who sustained an injury below the level of the knee were included for review. Seventy-three patients were included in this review. The results revealed that patients who developed a complication were significantly older than the group of patients without complications (P = .03). Digits were found to be injured most often but the odds of developing a complication were much higher if these injuries involved the plantar foot, dorsal foot, or ankle. Interestingly, patients on prolonged antibiotic therapy had a significantly higher risk of developing complications. The presence of comorbidities significantly increased the risk of complication (P = .008); the greatest risk factors were cardiovascular disease (P = .001) and diabetes (P = .06). The authors present the largest cohort of lawn mower injuries in the medical literature, which demonstrates that factors such as age, location of injury, and the presence of comorbidities influence the outcome and increase the risk of injury to the foot and ankle. These results may be useful in determining the best treatment plan possible for patients with these severe injuries. Therapeutic, Level IV, Retrospective case series.

Emerging Therapeutic Approaches to Mitochondrial Diseases

Science.gov (United States)

Wenz, Tina; Williams, Sion L.; Bacman, Sandra R.; Moraes, Carlos T.

2010-01-01

Mitochondrial diseases are very heterogeneous and can affect different tissues and organs. Moreover, they can be caused by genetic defects in either nuclear or mitochondrial DNA as well as by environmental factors. All of these factors have made the development of therapies difficult. In this review article, we will discuss emerging approaches to…

Vision rehabilitation interventions following mild traumatic brain injury: a scoping review.

Science.gov (United States)

Simpson-Jones, Mary E; Hunt, Anne W

2018-04-10

To broadly examine the literature to identify vision interventions following mild traumatic brain injury. Objectives are to identify: (1) evidence-informed interventions for individuals with visual dysfunction after mild traumatic brain injury; (2) professions providing these interventions; (3) gaps in the literature and areas for further research. A scoping review was conducted of four electronic databases of peer-reviewed literature from the databases earliest records to June 2017. Articles were included if the study population was mild traumatic brain injury/concussion and a vision rehabilitation intervention was tested. Two independent reviewers screened articles for inclusion, extracted data, and identified themes. The initial search identified 3111 records. Following exclusions, 22 articles were included in the final review. Nine studies evaluated optical devices, such as corrective spectacles, contact lenses, prisms, or binasal occlusion. Two studies assessed vision therapy. Ten studies examined vision therapy using optical devices. One study investigated hyperbaric oxygen therapy. Optometrists performed these interventions in most of the studies. Future research should address quality appraisal of this literature, interventions that include older adult and pediatric populations, and interdisciplinary interventions. There are promising interventions for vision deficits following mild traumatic brain injury. However, there are multiple gaps in the literature that should be addressed by future research. Implications for Rehabilitation Mild traumatic brain injury may result in visual deficits that can contribute to poor concentration, headaches, fatigue, problems reading, difficulties engaging in meaningful daily activities, and overall reduced quality of life. Promising interventions for vision rehabilitation following mild traumatic brain injury include the use of optical devices (e.g., prism glasses), vision or oculomotor therapy (e.g., targeted exercises to

Compliant flooring to prevent fall-related injuries: a scoping review protocol.

Science.gov (United States)

Lachance, Chantelle C; Jurkowski, Michal P; Dymarz, Ania C; Mackey, Dawn C

2016-08-16

Fall-related injuries can have serious consequences for older adults, including increased risk of dependence in daily activities and mortality. Compliant flooring is a passive intervention that may reduce the incidence and severity of fall-related injuries in healthcare settings, including acute and long-term care, but few sites have implemented compliant flooring, in part because synthesised evidence about key performance aspects has not been available. We will conduct a scoping review to address the question: what is presented about the biomechanical efficacy, clinical effectiveness, cost-effectiveness, and workplace safety associated with compliant flooring systems that aim to prevent fall-related injuries? We will conduct a comprehensive and systematic literature search of academic databases (AgeLine, CINAHL, EBM Reviews, MEDLINE (Ovid), SportDiscus and Web of Science) and grey literature (clinical trial registries, theses/dissertations, abstracts/conference proceedings and relevant websites). 2 team members will independently screen records (first titles and abstracts, then full text) and extract data from included records. Numerical and narrative analyses will be presented by theme (biomechanical efficacy, clinical effectiveness, cost-effectiveness, workplace safety). This scoping review responds to the information needs of healthcare decision-makers tasked with preventing fall-related injuries. This review will summarise evidence about compliant flooring as a potential intervention for preventing fall-related injuries in older adults and identify gaps in evidence and new avenues for research. Results will be especially useful in long-term care, but also applicable in acute care, assisted living and home care. We will disseminate the review's findings via open-access publications, conference presentations, a webinar, a Stakeholder Symposium and a Knowledge-to-Action Report. Published by the BMJ Publishing Group Limited. For permission to use (where not

Role of mitochondrial permeability transition in human renal tubular epithelial cell death induced by aristolochic acid

International Nuclear Information System (INIS)

Qi Xinming; Cai Yan; Gong Likun; Liu Linlin; Chen Fangping; Xiao Ying; Wu Xiongfei; Li Yan; Xue Xiang; Ren Jin

2007-01-01

Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a progressive tubulointerstitial nephropathy. However, the mechanism by which AA causes renal injury remains largely unknown. Here we reported that the mitochondrial permeability transition (MPT) plays an important role in the renal injury induced by aristolochic acid I (AAI). We found that in the presence of Ca 2+ , AAI caused mitochondrial swelling, leakage of Ca 2+ , membrane depolarization, and release of cytochrome c in isolated kidney mitochondria. These alterations were suppressed by cyclosporin A (CsA), an agent known to inhibit MPT. Culture of HK-2 cell, a human renal tubular epithelial cell line for 24 h with AAI caused a decrease in cellular ATP, mitochondrial membrane depolarization, cytochrome c release, and increase of caspase 3 activity. These toxic effects of AAI were attenuated by CsA and bongkrekic acid (BA), another specific MPT inhibitor. Furthermore, AAI greatly inhibited the activity of mitochondrial adenine nucleotide translocator (ANT) in isolated mitochondria. We suggested that ANT may mediate, at least in part, the AAI-induced MPT. Taken together, these results suggested that MPT plays a critical role in the pathogenesis of HK-2 cell injury induced by AAI and implied that MPT might contribute to human nephrotoxicity of aristolochic acid

Mitochondrial Dynamics in Type 2 Diabetes and Cancer

Directory of Open Access Journals (Sweden)

Michelle Williams

2018-04-01

Full Text Available Mitochondria are bioenergetic, biosynthetic, and signaling organelles that control various aspects of cellular and organism homeostasis. Quality control mechanisms are in place to ensure maximal mitochondrial function and metabolic homeostasis at the cellular level. Dysregulation of these pathways is a common theme in human disease. In this mini-review, we discuss how alterations of the mitochondrial network influences mitochondrial function, focusing on the molecular regulators of mitochondrial dynamics (organelle’s shape and localization. We highlight similarities and critical differences in the mitochondrial network of cancer and type 2 diabetes, which may be relevant for treatment of these diseases.

Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology.

Science.gov (United States)

Kulbe, Jacqueline R; Hall, Edward D

2017-11-01

In recent years, a new neurodegenerative tauopathy labeled Chronic Traumatic Encephalopathy (CTE), has been identified that is believed to be primarily a sequela of repeated mild traumatic brain injury (TBI), often referred to as concussion, that occurs in athletes participating in contact sports (e.g. boxing, American football, Australian football, rugby, soccer, ice hockey) or in military combatants, especially after blast-induced injuries. Since the identification of CTE, and its neuropathological finding of deposits of hyperphosphorylated tau protein, mechanistic attention has been on lumping the disorder together with various other non-traumatic neurodegenerative tauopathies. Indeed, brains from suspected CTE cases that have come to autopsy have been confirmed to have deposits of hyperphosphorylated tau in locations that make its anatomical distribution distinct for other tauopathies. The fact that these individuals experienced repetitive TBI episodes during their athletic or military careers suggests that the secondary injury mechanisms that have been extensively characterized in acute TBI preclinical models, and in TBI patients, including glutamate excitotoxicity, intracellular calcium overload, mitochondrial dysfunction, free radical-induced oxidative damage and neuroinflammation, may contribute to the brain damage associated with CTE. Thus, the current review begins with an in depth analysis of what is known about the tau protein and its functions and dysfunctions followed by a discussion of the major TBI secondary injury mechanisms, and how the latter have been shown to contribute to tau pathology. The value of this review is that it might lead to improved neuroprotective strategies for either prophylactically attenuating the development of CTE or slowing its progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications

Directory of Open Access Journals (Sweden)

Susana Rovira-Llopis

2017-04-01

Full Text Available Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1, mitofusin-2 (MFN2 and optic atrophy (OPA-1, while fission is controlled by mitochondrial fission 1 (FIS1, dynamin-related protein 1 (DRP1 and mitochondrial fission factor (MFF. PARKIN and (PTEN-induced putative kinase 1 (PINK1 participate in the process of mitophagy, for which mitochondrial fission is necessary. In this review, we discuss the molecular pathways of mitochondrial dynamics, their impairment under type 2 diabetes, and pharmaceutical approaches for targeting mitochondrial dynamics, such as mitochondrial division inhibitor-1 (mdivi-1, dynasore, P110 and 15-oxospiramilactone. Furthermore, we discuss the pathophysiological implications of impaired mitochondrial dynamics, especially in type 2 diabetes.

Melanocortin 4 Receptor Activation Attenuates Mitochondrial Dysfunction in Skeletal Muscle of Diabetic Rats.

Science.gov (United States)

Zhang, Hao-Hao; Liu, Jiao; Qin, Gui-Jun; Li, Xia-Lian; Du, Pei-Jie; Hao, Xiao; Zhao, Di; Tian, Tian; Wu, Jing; Yun, Meng; Bai, Yan-Hui

2017-11-01

A previous study has confirmed that the central melanocortin system was able to mediate skeletal muscle AMP-activated protein kinase (AMPK) activation in mice fed a high-fat diet, while activation of the AMPK signaling pathway significantly induced mitochondrial biogenesis. Our hypothesis was that melanocortin 4 receptor (MC4R) was involved in the development of skeletal muscle injury in diabetic rats. In this study, we treated diabetic rats intracerebroventricularly with MC4R agonist R027-3225 or antagonist SHU9119, respectively. Then, we measured the production of reactive oxygen species (ROS), the levels of malondialdehyde (MDA) and glutathione (GSH), the mitochondrial DNA (mtDNA) content and mitochondrial biogenesis, and the protein levels of p-AMPK, AMPK, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), sirtuin 1 (SIRT1), and manganese superoxide dismutase (MnSOD) in the skeletal muscle of diabetic rats. The results showed that there was significant skeletal muscle injury in the diabetic rats along with serious oxidative stress and decreased mitochondrial biogenesis. Treatment with R027-3225 reduced oxidative stress and induced mitochondrial biogenesis in skeletal muscle, and also activated the AMPK-SIRT1-PGC-1α signaling pathway. However, diabetic rats injected with MC4R antagonist SHU9119 showed an aggravated oxidative stress and mitochondrial dysfunction in skeletal muscle. In conclusion, our results revealed that MC4R activation was able to attenuate oxidative stress and mitochondrial dysfunction in skeletal muscle induced by diabetes partially through activating the AMPK-SIRT1-PGC-1α signaling pathway. J. Cell. Biochem. 118: 4072-4079, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Myotoxicity of injections for acute muscle injuries: A systematic review

NARCIS (Netherlands)

G. Reurink (Gustaaf); G.J. Goudswaard (Gert Jan); M.H. Moen (Maaike); A. Weir (Adam); J.A.N. Verhaar (Jan); J.L. Tol (Johannes)

2014-01-01

textabstractBackground: Injection therapies are widely used for muscle injuries. As there is only limited evidence of their efficacy, physicians should be aware of the potential harmful effects of these injected preparations. Objectives: The purpose of this review was to systematically review the

Alda-1 Protects Against Acrolein-Induced Acute Lung Injury and Endothelial Barrier Dysfunction.

Science.gov (United States)

Lu, Qing; Mundy, Miles; Chambers, Eboni; Lange, Thilo; Newton, Julie; Borgas, Diana; Yao, Hongwei; Choudhary, Gaurav; Basak, Rajshekhar; Oldham, Mahogany; Rounds, Sharon

2017-12-01

Inhalation of acrolein, a highly reactive aldehyde, causes lung edema. The underlying mechanism is poorly understood and there is no effective treatment. In this study, we demonstrated that acrolein not only dose-dependently induced lung edema but also promoted LPS-induced acute lung injury. Importantly, acrolein-induced lung injury was prevented and rescued by Alda-1, an activator of mitochondrial aldehyde dehydrogenase 2. Acrolein also dose-dependently increased monolayer permeability, disrupted adherens junctions and focal adhesion complexes, and caused intercellular gap formation in primary cultured lung microvascular endothelial cells (LMVECs). These effects were attenuated by Alda-1 and the antioxidant N-acetylcysteine, but not by the NADPH inhibitor apocynin. Furthermore, acrolein inhibited AMP-activated protein kinase (AMPK) and increased mitochondrial reactive oxygen species levels in LMVECs-effects that were associated with impaired mitochondrial respiration. AMPK total protein levels were also reduced in lung tissue of mice and LMVECs exposed to acrolein. Activation of AMPK with 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside blunted an acrolein-induced increase in endothelial monolayer permeability, but not mitochondrial oxidative stress or inhibition of mitochondrial respiration. Our results suggest that acrolein-induced mitochondrial dysfunction may not contribute to endothelial barrier dysfunction. We speculate that detoxification of acrolein by Alda-1 and activation of AMPK may be novel approaches to prevent and treat acrolein-associated acute lung injury, which may occur after smoke inhalation.

Sharps injuries in UK health care: a review of injury rates, viral transmission and potential efficacy of safety devices.

Science.gov (United States)

Elder, Alexander; Paterson, Caron

2006-12-01

To review the literature on sharps injuries and occupational bloodborne virus transmission in health care in the UK and the worldwide evidence for injury prevention of sharps safety devices. Literature review by online database and Internet resource search. Twenty-four relevant publications were identified regarding UK reported sharps injury rates. UK studies showed as much as a 10-fold difference between injuries reported through standard reporting systems (0.78-5.15 per 100 person-years) and rates estimated from retrospective questionnaires of clinical populations (30-284 per 100 person-years). National surveillance data from England, Wales and Northern Ireland gives a rate of 1.43 known hepatitis C virus or human immunodeficiency virus (HIV) transmissions to health care workers per annum. When extrapolated, this suggests an approximate rate of 0.009 such viral transmissions per 1000 hospital beds per annum. Risk of infection from sources with no risk factors is extremely small (less than one in one million for HIV transmission based on Scottish data). Thirty-one studies on the efficacy of sharps safety devices showed evidence of a reduction in injuries, with the greatest reductions achieved by blunt suture needles and safety cannulae. Although injuries remain common, confirmed viral transmission in the UK has been relatively rare. The degree of under-reporting of sharps injuries may be as much as 10-fold. Safety-engineered devices are likely to be effective at injury reduction.

Epidemiology of worldwide spinal cord injury: a literature review

Directory of Open Access Journals (Sweden)

Kang Y

2017-12-01

Full Text Available Yi Kang,1,2,* Han Ding,1,2,* Hengxing Zhou,1,2 Zhijian Wei,1,2 Lu Liu,1,2 Dayu Pan,1,2 Shiqing Feng1,2 1Department of Orthopaedics, Tianjin Medical University General Hospital, 2Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, People’s Republic of China *These authors contributed equally to this work Study design: A literature review of worldwide epidemiology of spinal cord injury (SCI. Objectives: To review the epidemiological indicators of SCI, such as incidence, prevalence, demographic characteristics, etiology, level and severity of injury, complications and mortality. Setting: The Department of Orthopaedics, Tianjin Medical University General Hospital, ­Heping District, Tianjin, People’s Republic of China. Methods: We searched articles published in PubMed, Medline, EMBASE and the Web of ­Science between January 1993 and June 2017 using the key words “spinal cord injury”, “­traumatic spinal cord injury”, “non-traumatic spinal cord injury” and “epidemiology”. The incidence, etiology, prevalence, patient demographics, level and severity of injury, complications and mortality were reviewed from the articles. Results: The epidemiology of SCI has changed. Motor vehicle accidents and falls have become the most common reasons of injury gradually. Incidence of SCI varies by regions or countries, and it has gradually increased with the expansion of human activities. The number of male patients were significantly more than female, the average age of patients with SCI had a tendency to increase gradually. The cervical level of spine was the most common part of injury; there were more number of patients with tetraplegia than patients with paraplegia. Electrolyte disturbances, pulmonary infections, urinary tract infections and bedsores were the four most common complications. Conclusion: We must have a greater

Orthopedic Injuries and Their Treatment in Children During Earthquakes: A Systematic Review.

Science.gov (United States)

Morelli, Ilaria; Sabbadini, Maria Grazia; Bortolin, Michelangelo

2015-10-01

Orthopedic injuries commonly affect children during earthquakes, but reports about them are rare. This setting may lead to different standards of care, but guidelines are still missing in this field. A systematic review was performed to: (1) assess type and body distribution of pediatric earthquake-related injuries, treatment performed, length of stay, and complications; and (2) identify starting points to define standards of care. PubMed database was researched for papers (1999-2014 period) in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Inclusion criteria were: English, French, Spanish, or Italian language and data reported about orthopedic lesions in children (≤18 years old). Reviews, letters, commentaries, editorials, and single case reports were excluded. Two independent reviewers selected articles after abstract and full-text reading. Traumatic injuries caused child hospital admissions ranging from 46.9% to 100.0%; 16% to 53% suffered fractures. Lower limbs mostly were involved. Soft-tissue injuries affected 55% of patients. Debridement and external fixation (EF) were the most frequent surgical treatments. Amputation rates varied from 5% to 11%. This study revealed that field hospitals should be prepared to: (1) treat mainly lower extremities fractures in children; and (2) use especially EF techniques. The presence of orthopedic surgeons familiar with pediatric traumatology should be considered.

Epidemiology of injuries in senior male rugby union sevens: a systematic review.

Science.gov (United States)

Cruz-Ferreira, Antonio; Cruz-Ferreira, Eduardo; Santiago, Luiz; Taborda Barata, Luis

2017-02-01

In 2016 the Rugby Union variant of sevens will enter the official Olympic Programme. Until now, most of injury surveillance studies in Rugby Union focus on elite 15-a-side cohorts, with reported injury incidence rates reaching 96 per 1000 player-match-hours, and mean severity set at 20 days. Sparse data is available regarding rugby sevens. The aim of this study was to systematically review available data regarding the epidemiology of injuries in senior male rugby sevens. Electronic databases (Pubmed, Google Scholar, SCOPUS, Scielo and IndexRMP) were searched in September 2015, complemented by manual searches of bibliographies and relevant "grey literature". Seven prospective cohort original articles addressing injuries in senior male rugby sevens players were included in this review. Overall injury incidence rates in elite rugby sevens tournaments ranged 101.5 to 119.8 per 1000 player-match-hours. Mean severity was greater than 34.1 days. Lower limb and joint/ligament injuries were the most frequent in elite players. The only study on amateur players revealed a lower injury incidence rate (74.7 per 1000 player-match-hours), and a higher proportion of muscle/tendon (37.5 %) injuries. Injury incidence rates in rugby sevens are higher than those reported for the 15-a-side variant, at the same level of competition. Injuries are also more severe, resulting in longer absence periods. This might result from the fact that rugby sevens is played with greater speed, leading to an increase in energy transfers during tackles, more running and turning manoeuvers, that can possibly cause more severe injuries.

The Epidemiology of Injuries in Mixed Martial Arts: A Systematic Review and Meta-analysis.

Science.gov (United States)

Lystad, Reidar P; Gregory, Kobi; Wilson, Juno

2014-01-01

Mixed martial arts (MMA) has experienced a surge in popularity since emerging in the 1990s, but the sport has also faced concomitant criticism from public, political, and medical holds. Notwithstanding the polarized discourse concerning the sport, no systematic review of the injury problems in MMA has been published to date. To systematically review the epidemiologic data on injuries in MMA and to quantitatively estimate injury incidence and risk factor effect sizes. Systematic review and meta-analysis; Level of evidence, 4. Electronic searching of PubMed, Scopus, CINAHL, EMBASE, AMED, and SPORTDiscus databases to identify studies reporting on the epidemiology of injuries in MMA. Random-effects models were used to obtain pooled summary estimates of the injury incidence rate per 1000 athlete-exposures (IIRAE) and rate ratios with 95% confidence intervals (CIs). Heterogeneity was evaluated with the I (2) statistic. A total of 6 studies were eligible for inclusion in this review. The IIRAE summary estimate was found to be 228.7 (95% CI, 110.4-473.5). No studies reported injury severity. The most commonly injured anatomic region was the head (range, 66.8%-78.0%) followed by the wrist/hand (range, 6.0%-12.0%), while the most frequent injury types were laceration (range, 36.7%-59.4%), fracture (range, 7.4%-43.3%), and concussion (range, 3.8%-20.4%). The most notable risk factors pertained to the outcome of bouts. Losers incurred 3 times as many injuries as winners, and fighters in bouts ending with knockout or technical knockout incurred more than 2 times as many injuries as fighters in bouts ending with submission. Notwithstanding the paucity of data, the injury incidence in MMA appears to be greater than in most, if not all, other popular and commonly practiced combat sports. In general, the injury pattern in MMA is very similar to that in professional boxing but unlike that found in other combat sports such as judo and taekwondo. More epidemiologic research is

Anterior cruciate ligament injury/reinjury in alpine ski racing: a narrative review

Science.gov (United States)

Jordan, Matthew J; Aagaard, Per; Herzog, Walter

2017-01-01

The purpose of the present review was to: 1) provide an overview of the current understanding on the epidemiology, etiology, risk factors, and prevention methods for anterior cruciate ligament (ACL) injury in alpine ski racing; and 2) provide an overview of what is known pertaining to ACL reinjury and return to sport after ACL injury in alpine ski racing. Given that most of the scientific studies on ACL injuries in alpine ski racing have been descriptive, and that very few studies contributed higher level scientific evidence, a nonsystematic narrative review was employed. Three scholarly databases were searched for articles on ACL injury or knee injury in alpine ski racing. Studies were classified according to their relevance in relation to epidemiology, etiology, risk factors, and return to sport/reinjury prevention. Alpine ski racers (skiers) were found to be at high risk for knee injuries, and ACL tears were the most frequent diagnosis. Three primary ACL injury mechanism were identified that involved tibial internal rotation and anteriorly directed shear forces from ski equipment and the environment. While trunk muscle strength imbalance and genetics were found to be predictive of ACL injuries in development-level skiers, there was limited scientific data on ACL injury risk factors among elite skiers. Based on expert opinion, research on injury risk factors should focus on equipment design, course settings/speed, and athlete factors (eg, fitness). While skiers seem to make a successful recovery following ACL injury, there may be persistent neuromuscular deficits. Future research efforts should be directed toward prospective studies on ACL injury/reinjury prevention in both male and female skiers and toward the effects of knee injury on long-term health outcomes, such as the early development of osteoarthritis. International collaborations may be necessary to generate sufficient statistical power for ACL injury/reinjury prevention research in alpine ski racing

Vocal Fold Epithelial Barrier in Health and Injury A Research Review

Science.gov (United States)

Levendoski, Elizabeth Erickson; Leydon, Ciara; Thibeault, Susan L.

2015-01-01

Purpose Vocal fold epithelium is composed of layers of individual epithelial cells joined by junctional complexes constituting a unique interface with the external environment. This barrier provides structural stability to the vocal folds and protects underlying connective tissue from injury while being nearly continuously exposed to potentially hazardous insults including environmental or systemic-based irritants such as pollutants and reflux, surgical procedures, and vibratory trauma. Small disruptions in the epithelial barrier may have a large impact on susceptibility to injury and overall vocal health. The purpose of this article is to provide a broad-based review of our current knowledge of the vocal fold epithelial barrier. Methods A comprehensive review of the literature was conducted. Details of the structure of the vocal fold epithelial barrier are presented and evaluated in the context of function in injury and pathology. The importance of the epithelial-associated vocal fold mucus barrier is also introduced. Results/Conclusions Information presented in this review is valuable for clinicians and researchers as it highlights the importance of this understudied portion of the vocal folds to overall vocal health and disease. Prevention and treatment of injury to the epithelial barrier is a significant area awaiting further investigation. PMID:24686981

Quality of life following road traffic injury: A systematic literature review.

Science.gov (United States)

Rissanen, Ritva; Berg, Hans-Yngve; Hasselberg, Marie

2017-11-01

To assess and provide a systematic overview of current knowledge about the relationship between quality of life (QoL) and road traffic injury, and to appraise how QoL is affected by road traffic injury. A systematic review of the literature published since 1990 on QoL after a road traffic injury, including adult and paediatric populations, from three databases (Pubmed, PsychInfo and SafetyLit) was undertaken. The methodological quality was assessed according to the Newcastle-Ottawa Quality Assessment Scale. Thirty articles were included and assessed for quality. The QoL scores of those injured were similar to population norms at the first assessment, followed by a drop at the second assessment. An increase of QoL from the second to third assessment was reported, but participants never reached the population norms at the last follow-up (range six weeks to two years), with an exception of those claiming compensation and those with lower extremity fractures. Age, gender, socioeconomic status, injury severity, injury type and post-traumatic stress disorder were associated with reduced QoL. Available literature regarding QoL among injured in road traffic crashes is heterogeneous with regard to aims and tools used for assessment. Our review confirmed that independent of measure, the overall QoL was significantly reduced after a road traffic injury compared to the general population norms. Persons who are older, of female gender, lower socioeconomic status, diagnosed with post-traumatic stress disorder, with more severe injuries or injuries to the lower limbs are more vulnerable to loss of QoL following road traffic injury compared to other patient groups injured in road traffic crashes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Family function and its relationship to injury severity and psychiatric outcome in children with acquired brain injury: a systematized review.

Science.gov (United States)

Lax Pericall, Maria Teresa; Taylor, Eric

2014-01-01

The psychological and psychiatric outcome of children with acquired brain injury is influenced by many variables. A review was undertaken to clarify the contribution of family function, how it relates to injury severity, and what particular aspects of family function influence psychological outcome in this group. A systematized review of the literature of studies published between 1970 and 2012 from OvidMedline, PsychoInfo, PsycARTICLES, and Cochrane was undertaken focusing on family function, injury severity, and psychiatric outcome. Thirty-six papers met the inclusion criteria. Injury severity was linked to the development of organic personality change. Family function before injury, measured by the Family Assessment Device or the Clinical Rating Scale, had a statistically significant effect on general psychological functioning in six out of eight studies. Family function had a significant effect for oppositional defiant disorder and secondary attention-deficit-hyperactivity disorder. The effects of family function may differ depending on the age of the child and the severity of the injury. Some styles of parenting moderated recovery. After injury, family function was related to the child's contemporaneous psychiatric symptoms. The level of evidence for these papers was 3 or 4 (Oxford Centre for Evidence-based Medicine criteria). Screening for some aspects of family functioning before injury and family function during the rehabilitation phase may identify children at risk of psychiatric disorders. © 2013 Mac Keith Press.

Mitochondrial oxidative stress in human hepatoma cells exposed to stavudine

International Nuclear Information System (INIS)

Velsor, Leonard W.; Kovacevic, Miro; Goldstein, Mark; Leitner, Heather M.; Lewis, William; Day, Brian J.

2004-01-01

The toxicity of nucleoside reverse transcriptase inhibitors (NRTIs) is linked to altered mitochondrial DNA (mtDNA) replication and subsequent disruption of cellular energetics. This manifests clinically as elevated concentrations of lactate in plasma. The mechanism(s) underlying how the changes in mtDNA replication lead to lactic acidosis remains unclear. It is hypothesized that mitochondrial oxidative stress links the changes in mtDNA replication to mitochondrial dysfunction and ensuing NRTIs toxicity. To test this hypothesis, changes in mitochondrial function, mtDNA amplification efficiency, and oxidative stress were assessed in HepG2-cultured human hepatoblasts treated with the NRTI stavudine (2',3'-didehydro-2',3'-deoxythymidine or d4T) for 48 h. d4T produced significant mitochondrial dysfunction with a 1.5-fold increase in cellular lactate to pyruvate ratios. In addition, d4T caused a dose-dependent decrease in mtDNA amplification and a correlative increase in abundance of markers of mitochondrial oxidative stress. Manganese (III) meso-tetrakis (4-benzoic acid) porphyrin, MnTBAP, a catalytic antioxidant, ameliorated or reversed d4T-induced changes in cell injury, energetics, mtDNA amplification, and mitochondrial oxidative stress. In conclusion, d4T treatment elevates mitochondrial reactive oxygen species (ROS), enhances mitochondrial oxidative stress, and contributes mechanistically to NRTI-induced toxicity. These deleterious events may be potentiated in acquired immunodeficiency syndrome (AIDS) by human immunodeficiency virus (HIV) infection itself, coinfection (e.g., viral hepatitis), aging, substance, and alcohol use

Mitochondrial-epigenetic crosstalk in environmental toxicology.

Science.gov (United States)

Weinhouse, Caren

2017-11-01

Crosstalk between the nuclear epigenome and mitochondria, both in normal physiological function and in responses to environmental toxicant exposures, is a developing sub-field of interest in environmental and molecular toxicology. The majority (∼99%) of mitochondrial proteins are encoded in the nuclear genome, so programmed communication among nuclear, cytoplasmic, and mitochondrial compartments is essential for maintaining cellular health. In this review, we will focus on correlative and mechanistic evidence for direct impacts of each system on the other, discuss demonstrated or potential crosstalk in the context of chemical insult, and highlight biological research questions for future study. We will first review the two main signaling systems: nuclear signaling to the mitochondria [anterograde signaling], best described in regulation of oxidative phosphorylation (OXPHOS) and mitochondrial biogenesis in response to environmental signals received by the nucleus, and mitochondrial signals to the nucleus [retrograde signaling]. Both signaling systems can communicate intracellular energy needs or a need to compensate for dysfunction to maintain homeostasis, but both can also relay inappropriate signals in the presence of dysfunction in either system and contribute to adverse health outcomes. We will first review these two signaling systems and highlight known or biologically feasible epigenetic contributions to both, then briefly discuss the emerging field of epigenetic regulation of the mitochondrial genome, and finally discuss putative "crosstalk phenotypes", including biological phenomena, such as caloric restriction, maintenance of stemness, and circadian rhythm, and states of disease or loss of function, such as cancer and aging, in which both the nuclear epigenome and mitochondria are strongly implicated. Copyright © 2017 Elsevier B.V. All rights reserved.

Mitochondrial permeability transition and cell death: the role of cyclophilin D

Directory of Open Access Journals (Sweden)

Sabzali eJavadov

2013-04-01

Full Text Available Mitochondria serve as a powerhouse which provides near 90% of ATP necessary for cell life. However, recent studies provide strong evidence that mitochondria also play a central role in cell death. Irreversible mitochondrial permeability transition (mPT at high conductance in response to oxidative or other cellular stresses is accompanied by formation of pathological and non-specific mPT pores (mPTP in the inner membrane of mitochondria. Mitochondrial PTP can serve as a target to prevent cell death under pathological conditions such as cardiac and brain ischemia/reperfusion injury and diabetes. On the other hand, mPTP can be used as an executioner to specifically induce cell death thus blocking tumorigenesis in cancer diseases. Despite many studies, the molecular identity of the mPTP remains unclear. At present, cyclophilin D (CyP-D represents the only mPTP protein which plays an essential role in pore formation. This review will discuss direct and indirect mechanisms underlying CyP-D interaction with a target protein of the mPTP complex. Understanding of the mechanisms of mPTP formation will be helpful to further develop new pharmacological agents targeting mitochondria-mediated cell death.

Myotoxicity of injections for acute muscle injuries: a systematic review

NARCIS (Netherlands)

Reurink, Gustaaf; Goudswaard, Gert Jan; Moen, Maarten H.; Weir, Adam; Verhaar, Jan A. N.; Tol, Johannes L.

2014-01-01

Injection therapies are widely used for muscle injuries. As there is only limited evidence of their efficacy, physicians should be aware of the potential harmful effects of these injected preparations. The purpose of this review was to systematically review the literature on the myotoxic effects of

Mitochondrial bioenergetics during the initiation of mercuric chloride-induced renal injury. I. Direct effects of in vitro mercuric chloride on renal cortical mitochondrial function

Energy Technology Data Exchange (ETDEWEB)

Weinberg, J.M. (Veterans Administration Medical Center, Ann Arbor, MI); Harding, P.G.; Humes, H.D.

1982-01-01

Increasing data suggest that mitochondrial dysfunction may be an important early component of nephrotoxin-induced changes in renal cell function and viability. This study was designed to obtain more detailed information about the effects on several basic bioenergetic parameters of the direct interaction of Hg/sup 2 +/ with renal cortical mitochondria in vitro as a necessary prelude to studies of mitochondrial functional changes after treatment with mercuric chloride in vivo. Beginning at a threshhold level of 2 nmol of Hg/sup 2 +//mg of mitochondrial protein Hg/sup 2 +/ induced marked stimulation of State 4 respiration, mild inhibition of State 3 respiration, and 2,4-dinitrophenol uncoupled respiration, a striking increase in atractyloside-insensitive ADP uptake and stimulation of both basal- and Mg/sup 2 +/-activated oligomycin-sensitive mitochondrial ATPase activity. These effects of Hg/sup 2 +/ could be prevented and reversed by the sulfhydryl reagent dithioerythritol and by albumin but were not affected by Mg/sup 2 +/. Detailed studies on the addition of HgCl/sub 2/ to the preparation at different stages of the mitochondrial isolation procedure demonstrated that the presence of other proteins decreased mitochondrial Hg/sup 2 +/ binding, that the Hg/sup 2 +/ was not readily washed off the mitochondria by nonprotein-containing solutions, and that prolonged exposure of mitochondria to Hg/sup 2 +/ during the isolation procedure did not markedly alter its functional effects on their reversibility as assessed on the final mitochondrial preparation. These data provide an important basis for critically assessing the changes in function of mitochondria isolated after in vivo treatment with mercuric chloride.

Targeted Modification of Mitochondrial ROS Production Converts High Glucose-Induced Cytotoxicity to Cytoprotection: Effects on Anesthetic Preconditioning.

Science.gov (United States)

Sedlic, Filip; Muravyeva, Maria Y; Sepac, Ana; Sedlic, Marija; Williams, Anna Marie; Yang, Meiying; Bai, Xiaowen; Bosnjak, Zeljko J

2017-01-01

Contradictory reports on the effects of diabetes and hyperglycemia on myocardial infarction range from cytotoxicity to cytoprotection. The study was designed to investigate acute effects of high glucose-driven changes in mitochondrial metabolism and osmolarity on adaptive mechanisms and resistance to oxidative stress of isolated rat cardiomyocytes. We examined the effects of high glucose on several parameters of mitochondrial bioenergetics, including changes in oxygen consumption, mitochondrial membrane potential, and NAD(P)H fluorometry. Effects of high glucose on the endogenous cytoprotective mechanisms elicited by anesthetic preconditioning (APC) and the mediators of cell injury were also tested. These experiments included real-time measurements of reactive oxygen species (ROS) production and mitochondrial permeability transition pore (mPTP) opening in single cells by laser scanning fluorescence confocal microscopy, and cell survival assay. High glucose rapidly enhanced mitochondrial energy metabolism, observed by increase in NAD(P)H fluorescence intensity, oxygen consumption, and mitochondrial membrane potential. This substantially elevated production of ROS, accelerated opening of the mPTP, and decreased survival of cells exposed to oxidative stress. Abrogation of high glucose-induced mitochondrial hyperpolarization with 2,4 dinitrophenol (DNP) significantly, but not completely, attenuated ROS production to a level similar to hyperosmotic mannitol control. DNP treatment reversed high glucose-induced cytotoxicity to cytoprotection. Hyperosmotic mannitol treatment also induced cytoprotection. High glucose abrogated APC-induced mitochondrial depolarization, delay in mPTP opening and cytoprotection. In conclusion, high glucose-induced mitochondrial hyperpolarization abolishes APC and augments cell injury. Attenuation of high glucose-induced ROS production by eliminating mitochondrial hyperpolarization protects cardiomyocytes. J. Cell. Physiol. 232: 216-224, 2017

Deconstructing Mitochondrial Dysfunction in Alzheimer Disease

Directory of Open Access Journals (Sweden)

Vega García-Escudero

2013-01-01

Full Text Available There is mounting evidence showing that mitochondrial damage plays an important role in Alzheimer disease. Increased oxygen species generation and deficient mitochondrial dynamic balance have been suggested to be the reason as well as the consequence of Alzheimer-related pathology. Mitochondrial damage has been related to amyloid-beta or tau pathology or to the presence of specific presenilin-1 mutations. The contribution of these factors to mitochondrial dysfunction is reviewed in this paper. Due to the relevance of mitochondrial alterations in Alzheimer disease, recent works have suggested the therapeutic potential of mitochondrial-targeted antioxidant. On the other hand, autophagy has been demonstrated to play a fundamental role in Alzheimer-related protein stress, and increasing data shows that this pathway is altered in the disease. Moreover, mitochondrial alterations have been related to an insufficient clearance of dysfunctional mitochondria by autophagy. Consequently, different approaches for the removal of damaged mitochondria or to decrease the related oxidative stress in Alzheimer disease have been described. To understand the role of mitochondrial function in Alzheimer disease it is necessary to generate human cellular models which involve living neurons. We have summarized the novel protocols for the generation of neurons by reprogramming or direct transdifferentiation, which offer useful tools to achieve this result.

Does generalized joint hypermobility predict joint injury in sport? A review.

LENUS (Irish Health Repository)

Donaldson, Peter R

2012-02-01

OBJECTIVE: To determine whether persons with generalized joint hypermobility have an increased risk of lower limb joint injury during sport. DATA SOURCES: PubMed, CINAHL, EMBASE, and SportDiscus were searched through February 2009, without language restrictions, using terms related to risk; hip, ankle, and knee injuries; and joint instability. Reference lists of included studies and relevant reviews were searched by hand. STUDY SELECTION: Selection criteria were peer-reviewed studies with a prospective design that used an objective scale to measure generalized joint hypermobility; the participants were engaged in sport activity, and the injury data were quantitative and based on diagnosis by a health professional, were self-reported, or resulted in time lost to athletic participation. The studies were screened by 1 researcher and checked by a second. Study methods were independently assessed by 2 investigators using the 6-point scale for prognostic studies developed by Pengel. Disagreements were resolved through discussion. Of 4841 studies identified, 18 met inclusion criteria. Of these, 8 were included in random-effects meta-analyses. DATA EXTRACTION: The data extracted by 2 reviewers included participant and sport characteristics and details of joint hypermobility and injury measurements. More detailed data for 4 investigations were obtained from the study authors. Where possible, hypermobility was defined as >\\/=4 of 9 points on the British Society of Rheumatology Scale (BSRS). MAIN RESULTS: Lower limb joint injuries (3 studies, 1047 participants) occurred in 14% of participants. Using the BSRS of joint hypermobility, any lower limb injury was not associated with hypermobility [odds ratio (OR), 1.43; 95% confidence interval (CI), 0.56-3.67]. Using the original authors\\' definitions, hypermobility was associated with risk of knee joint injuries (OR, 2.62; 95% CI, 1.04-6.58) in 5 studies. In 4 studies in which the BSRS could be used (1167 participants; incidence

The expanding phenotype of mitochondrial myopathy.

Science.gov (United States)

DiMauro, Salvatore; Gurgel-Giannetti, Juliana

2005-10-01

Our understanding of mitochondrial diseases (defined restrictively as defects in the mitochondrial respiratory chain) continues to progress apace. In this review we provide an update of information regarding disorders that predominantly or exclusively affect skeletal muscle. Most recently described mitochondrial myopathies are due to defects in nuclear DNA, including coenzyme Q10 deficiency, and mutations in genes that control mitochondrial DNA (mtDNA) abundance and structure such as POLG and TK2. Barth syndrome, an X-linked recessive mitochondrial myopathy/cardiopathy, is associated with altered lipid composition of the inner mitochondrial membrane, but a putative secondary impairment of the respiratory chain remains to be documented. Concerning the 'other genome', the role played by mutations in protein encoding genes of mtDNA in causing isolated myopathies has been confirmed. It has also been confirmed that mutations in tRNA genes of mtDNA can cause predominantly myopathic syndromes and - contrary to conventional wisdom - these mutations can be homoplasmic. Defects in the mitochondrial respiratory chain impair energy production and almost invariably involve skeletal muscle, causing exercise intolerance, myalgia, cramps, or fixed weakness, which often affects extraocular muscles and results in droopy eyelids (ptosis) and progressive external ophthalmoplegia.

Current Experience in Testing Mitochondrial Nutrients in Disorders Featuring Oxidative Stress and Mitochondrial Dysfunction: Rational Design of Chemoprevention Trials

OpenAIRE

Giovanni Pagano; Annarita Aiello Talamanca; Giuseppe Castello; Mario D. Cordero; Marco d'Ischia; Maria Nicola Gadaleta; Federico V. Pallardó; Sandra Petrović; Luca Tiano; Adriana Zatterale

2014-01-01

An extensive number of pathologies are associated with mitochondrial dysfunction (MDF) and oxidative stress (OS). Thus, mitochondrial cofactors termed “mitochondrial nutrients” (MN), such as α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and l-carnitine (CARN) (or its derivatives) have been tested in a number of clinical trials, and this review is focused on the use of MN-based clinical trials. The papers reporting on MN-based clinical trials were retrieved in MedLine up to July 2014, and evaluat...

Trampolines revisited: a review of 114 pediatric recreational trampoline injuries.

Science.gov (United States)

Woodward, G A; Furnival, R; Schunk, J E

1992-05-01

A search of the medical literature failed to reveal any articles that discuss pediatric injuries acquired on privately owned recreational trampolines. This study was undertaken to quantify and qualify pediatric injuries from recreational trampoline use. A group of 114 patients who presented to the Emergency Department at Primary Children's Medical Center in Salt Lake City, Utah, with injuries directly related to use of a trampoline are discussed. There was a 1.2:1 male-female ratio. The average age was 8.0 years. Forty-eight percent of the patients were injured on their family's trampoline, with the remainder injured on a friend's, neighbor's, relative's, or gymnasium's equipment. The majority of injuries involved group use of the trampoline and the youngest person in a group was most often the injured participant. Extremity injuries were seen in 55% of the patient and head or neck injuries in 37%. Seventy-five percent of the patients required radiographs, 23% hospitalization, and 17% operative intervention. The history of the trampoline and medical literature discussions concerning injuries and safety are reviewed.

Epidemiology of Figure Skating Injuries: A Review of the Literature.

Science.gov (United States)

Han, Julie S; Geminiani, Ellen T; Micheli, Lyle J

2018-05-01

As the popularity and technical demands of figure skating increase, so will the number of athletes presenting with sport-related problems. Searches were performed across PubMed from 1980 to 2017. The keywords searched were skating, skaters, incidence, and injuries. The search was limited to English-language articles and human participants. Relevant articles were cross-referenced. Clinical review. Level 5. Previous studies suggest an increase in incidence of figure skating injuries from 1982 to 2003. When combining all disciplines of figure skating, there is a similar proportion of acute and overuse injuries. Within disciplines, overuse injuries appear to be more common in singles skating, while acute injuries are more common in pairs skating, ice dancing, and synchronized skating. Lower extremity injuries are more common than upper extremity injuries in all disciplines, and pairs skating accounts for the majority of upper extremity injuries. Ankle sprains are the most common skating injury, and patellar tendinitis is the most common overuse injury across all disciplines. Stress fractures are the most common overuse injury in female singles skaters. The predominance of overuse injuries in singles disciplines reflects their increasing technical difficulty, with more difficult jumps and longer training hours. Partner disciplines are more likely to involve acute injuries and upper extremity injuries due to high-risk throws and lifts. Emphasis should be placed on properly fitting skating boots, intrinsic foot and ankle strengthening, and lower extremity flexibility, which may prevent many of the common lower extremity and back injuries in figure skating.

Sexuality following trauma injury: A literature review

Directory of Open Access Journals (Sweden)

Kylie Marie Connell

2014-04-01

Full Text Available Restoration of the quality of life (QoL of trauma injury survivors is the aim of trauma rehabilitation. It is generally acknowledged that sexuality is an important component of QoL; however, rehabilitation services frequently fall short of including sexuality as a matter of routine. The literature was reviewed to examine the experiences of trauma survivors from three groups: spinal cord injury (SCI, traumatic brain injury (TBI and burns. The focus was on the impact of trauma on the QoL to identify future research directions and to advocate for the inclusion of sexuality as an integral part of rehabilitation. Databases searched were Proquest, Ovid, Cinahl, Medline, PsycInfo and Cochrane Central Register of controlled trials. A total of 36 eligible studies were included: SCI (n = 25, TBI (n = 6, burns (n = 5. Four themes were identified across the three trauma groups that were labeled as physiological impact of trauma on sexuality, cognitive-genital dissociation (CGD, sexual disenfranchisement (SD and sexual rediscovery (SR. Trauma injury has a significant impact on sexuality, which is not routinely addressed within rehabilitation services. Further sexuality research is required among all trauma groups to improve rehabilitation services and in turn QoL outcomes for all trauma survivors.

Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression

Directory of Open Access Journals (Sweden)

Francesco Bellanti

2018-05-01

Full Text Available The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury.

Pharmacological modulation of mitochondrial calcium homeostasis.

Science.gov (United States)

Arduino, Daniela M; Perocchi, Fabiana

2018-01-10

Mitochondria are pivotal organelles in calcium (Ca 2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca 2+ homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases. Efforts have been taken to harness mitochondrial Ca 2+ transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca 2+ homeostasis are currently lacking. New avenues have, however, emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca 2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca 2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progress towards a systems-level pharmacological targeting of mitochondrial Ca 2+ homeostasis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Machine learning approaches to analysing textual injury surveillance data: a systematic review.

Science.gov (United States)

Vallmuur, Kirsten

2015-06-01

To synthesise recent research on the use of machine learning approaches to mining textual injury surveillance data. Systematic review. The electronic databases which were searched included PubMed, Cinahl, Medline, Google Scholar, and Proquest. The bibliography of all relevant articles was examined and associated articles were identified using a snowballing technique. For inclusion, articles were required to meet the following criteria: (a) used a health-related database, (b) focused on injury-related cases, AND used machine learning approaches to analyse textual data. The papers identified through the search were screened resulting in 16 papers selected for review. Articles were reviewed to describe the databases and methodology used, the strength and limitations of different techniques, and quality assurance approaches used. Due to heterogeneity between studies meta-analysis was not performed. Occupational injuries were the focus of half of the machine learning studies and the most common methods described were Bayesian probability or Bayesian network based methods to either predict injury categories or extract common injury scenarios. Models were evaluated through either comparison with gold standard data or content expert evaluation or statistical measures of quality. Machine learning was found to provide high precision and accuracy when predicting a small number of categories, was valuable for visualisation of injury patterns and prediction of future outcomes. However, difficulties related to generalizability, source data quality, complexity of models and integration of content and technical knowledge were discussed. The use of narrative text for injury surveillance has grown in popularity, complexity and quality over recent years. With advances in data mining techniques, increased capacity for analysis of large databases, and involvement of computer scientists in the injury prevention field, along with more comprehensive use and description of quality

Epidemiology of ankle and foot overuse injuries in sports : A systematic review

NARCIS (Netherlands)

Sobhani, S.; Dekker, R.; Postema, K.; Dijkstra, P. U.

2013-01-01

Studies regarding ankle and foot overuse injuries are quite diverse in research methodology, data reporting, and outcomes. The aims of this systematic review were to analyze the methodology of published studies regarding ankle and foot overuse injuries in different sports disciplines and to

Pupillometric evaluation of the melanopsin containing retinal ganglion cells in mitochondrial and non-mitochondrial optic neuropathies

DEFF Research Database (Denmark)

Ba-Ali, Shakoor; Lund-Andersen, Henrik

2017-01-01

of pupillary light reflex is primarily driven by the ipRGCs. Optic neuropathies i.e. Leber hereditary optic neuropathy (LHON), autosomal dominant optic atrophy (ADOA), nonarteritic anterior ischemic optic neuropathy (NAION), glaucoma, optic neuritis and idiopathic intracranial hypertension (IIH) are among...... the diseases, which have been subject to pupillometric studies. The ipRGCs are differentially affected in these various optic neuropathies. In mitochondrial optic neuropathies, the ipRGCs are protected against degeneration, whereas in glaucoma, NAION, optic neuritis and IIH the ipRGCs are damaged. Here, we...... will review the results of pupillometric, histopathological and animal studies evaluating the ipRGCs in mitochondrial and non-mitochondrial optic neuropathies....

A Review of Family Intervention Guidelines for Pediatric Acquired Brain Injuries

Science.gov (United States)

Cole, Wesley R.; Paulos, Stephanie K.; Cole, Carolyn A. S.; Tankard, Carol

2009-01-01

Pediatric acquired brain injury (BI) not only affects the child with the injury, but also greatly impacts their family. Studies suggest there are higher rates of caregiver and sibling psychological distress after a child in the family has sustained a BI. Also, family functioning after BI impacts the child's recovery. In reviewing the literature,…

Mitochondrial toxicity of diclofenac and its metabolites via inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria

DEFF Research Database (Denmark)

Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

2016-01-01

Diclofenac is a widely prescribed NSAID, which by itself and its reactive metabolites (Phase-I and Phase-II) may be involved in serious idiosyncratic hepatotoxicity. Mitochondrial injury is one of the mechanisms of drug induced liver injury (DILI). In the present work, an investigation of the inh......Diclofenac is a widely prescribed NSAID, which by itself and its reactive metabolites (Phase-I and Phase-II) may be involved in serious idiosyncratic hepatotoxicity. Mitochondrial injury is one of the mechanisms of drug induced liver injury (DILI). In the present work, an investigation...... of the inhibitory effects of diclofenac (Dic) and its phase I [4-hydroxy diclofenac (4'-OH-Dic) and 5-hydroxy diclofenac (5-OH-dic)] and Phase-II [diclofenac acyl glucuronide (DicGluA) and diclofenac glutathione thioester (DicSG)] metabolites, on ATP synthesis in rat liver mitochondria was carried out. A mechanism...

Pressure injuries in people with darker skin tones: A literature review.

Science.gov (United States)

Oozageer Gunowa, Neesha; Hutchinson, Marie; Brooke, Joanne; Jackson, Debra

2017-09-08

In this article, we aimed to explore the literature to ascertain what research evidence exists in relation to the identification of pressure injuries in people with dark skin tones. Pressure injuries development has been widely researched and documented; however, much of this work does not address ethnicity or race and assumes Caucasian-ness. Thus, the perceptions of people with dark skin tones and the influence of skin pigmentation on identification and management of pressure injuries is under examined. Literature review. A comprehensive electronic database search was undertaken of PubMed, Cumulative Index for Nursing and Allied Health Literature, Cochrane and British Nursing Index (BNI) between 1990-July 2016. Alongside the electronic data, journals, books, papers from conferences, relevant national and international organisations and reference lists were also used to help source key studies. A search of the literature revealed 11 relevant articles. The foci of studies included the following: risk of sustaining a pressure injuries based on skin tones, identification of pressure injuries amongst people with dark skin tones, pressure injuries and place of care and socio-economic impact on pressure injuries development. Overall, findings indicate that people with darker skin tones are more likely to develop higher stage pressure injuries. Reasons for this are not fully elucidated; however, it may be associated with current skin assessment protocols being less effective for people who have darker skin tones resulting in early damage arising from pressure not being recognised. From the literature reviewed, it can be seen that there is a lack of guidance and evidence, and people with darker skin tones are more likely in comparison with people presenting as Caucasian to develop higher stage pressure injuries. The current literature suggests a need for researchers and clinicians to consider skin tone variances rather than ethnicity when exploring comprehensive skin

Mitochondrial dysfunction in obesity.

Science.gov (United States)

de Mello, Aline Haas; Costa, Ana Beatriz; Engel, Jéssica Della Giustina; Rezin, Gislaine Tezza

2018-01-01

Obesity leads to various changes in the body. Among them, the existing inflammatory process may lead to an increase in the production of reactive oxygen species (ROS) and cause oxidative stress. Oxidative stress, in turn, can trigger mitochondrial changes, which is called mitochondrial dysfunction. Moreover, excess nutrients supply (as it commonly is the case with obesity) can overwhelm the Krebs cycle and the mitochondrial respiratory chain, causing a mitochondrial dysfunction, and lead to a higher ROS formation. This increase in ROS production by the respiratory chain may also cause oxidative stress, which may exacerbate the inflammatory process in obesity. All these intracellular changes can lead to cellular apoptosis. These processes have been described in obesity as occurring mainly in peripheral tissues. However, some studies have already shown that obesity is also associated with changes in the central nervous system (CNS), with alterations in the blood-brain barrier (BBB) and in cerebral structures such as hypothalamus and hippocampus. In this sense, this review presents a general view about mitochondrial dysfunction in obesity, including related alterations, such as inflammation, oxidative stress, and apoptosis, and focusing on the whole organism, covering alterations in peripheral tissues, BBB, and CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

Mitochondrial Energy and Redox Signaling in Plants

Science.gov (United States)

Schwarzländer, Markus

2013-01-01

Abstract Significance: For a plant to grow and develop, energy and appropriate building blocks are a fundamental requirement. Mitochondrial respiration is a vital source for both. The delicate redox processes that make up respiration are affected by the plant's changing environment. Therefore, mitochondrial regulation is critically important to maintain cellular homeostasis. This involves sensing signals from changes in mitochondrial physiology, transducing this information, and mounting tailored responses, by either adjusting mitochondrial and cellular functions directly or reprogramming gene expression. Recent Advances: Retrograde (RTG) signaling, by which mitochondrial signals control nuclear gene expression, has been a field of very active research in recent years. Nevertheless, no mitochondrial RTG-signaling pathway is yet understood in plants. This review summarizes recent advances toward elucidating redox processes and other bioenergetic factors as a part of RTG signaling of plant mitochondria. Critical Issues: Novel insights into mitochondrial physiology and redox-regulation provide a framework of upstream signaling. On the other end, downstream responses to modified mitochondrial function have become available, including transcriptomic data and mitochondrial phenotypes, revealing processes in the plant that are under mitochondrial control. Future Directions: Drawing parallels to chloroplast signaling and mitochondrial signaling in animal systems allows to bridge gaps in the current understanding and to deduce promising directions for future research. It is proposed that targeted usage of new technical approaches, such as quantitative in vivo imaging, will provide novel leverage to the dissection of plant mitochondrial signaling. Antioxid. Redox Signal. 18, 2122–2144. PMID:23234467

Literature review on vehicle travel speeds and pedestrian injuries

Science.gov (United States)

1999-10-01

The relationship between vehicle travel speeds and resulting pedestrian injury was reviewed in the literature and in existing data sets. Results indicated that higher vehicle speeds are strongly associated with both a greater likelihood of pedestrian...

Descriptors Used to Define Running-Related Musculoskeletal Injury: A Systematic Review

NARCIS (Netherlands)

Yamato, T.P.; Saragiotto, B.T.; Hespanhol, L.C.; Yeung, S.S.; Lopes, A.D.

2015-01-01

STUDY DESIGN: Systematic review. OBJECTIVES: To systematically review the used to define running-related musculoskeletal injury and to analyze the implications of different definitions on the results of studies. BACKGROUND: Studies have developed their own definitions of running-related

Outer Mitochondrial Membrane Localization of Apoptosis-Inducing Factor: Mechanistic Implications for Release

Directory of Open Access Journals (Sweden)

Seong-Woon Yu

2009-10-01

Full Text Available Poly(ADP-ribose polymerase-1-dependent cell death (known as parthanatos plays a pivotal role in many clinically important events including ischaemia/reperfusion injury and glutamate excitotoxicity. A recent study by us has shown that uncleaved AIF (apoptosis-inducing factor, but not calpain-hydrolysed truncated-AIF, was rapidly released from the mitochondria during parthanatos, implicating a second pool of AIF that might be present in brain mitochondria contributing to the rapid release. In the present study, a novel AIF pool is revealed in brain mitochondria by multiple biochemical analyses. Approx. 30% of AIF loosely associates with the outer mitochondrial membrane on the cytosolic side, in addition to its main localization in the mitochondrial intermembrane space attached to the inner membrane. Immunogold electron microscopic analysis of mouse brain further supports AIF association with the outer, as well as the inner, mitochondrial membrane in vivo. In line with these observations, approx. 20% of uncleaved AIF rapidly translocates to the nucleus and functionally causes neuronal death upon NMDA (N-methyl-d-aspartate treatment. In the present study we show for the first time a second pool of AIF in brain mitochondria and demonstrate that this pool does not require cleavage and that it contributes to the rapid release of AIF. Moreover, these results suggest that this outer mitochondrial pool of AIF is sufficient to cause cell death during parthanatos. Interfering with the release of this outer mitochondrial pool of AIF during cell injury paradigms that use parthanatos hold particular promise for novel therapies to treat neurological disorders.

Loss of PINK1 increases the heart's vulnerability to ischemia-reperfusion injury.

Directory of Open Access Journals (Sweden)

Hilary K Siddall

Full Text Available Mutations in PTEN inducible kinase-1 (PINK1 induce mitochondrial dysfunction in dopaminergic neurons resulting in an inherited form of Parkinson's disease. Although PINK1 is present in the heart its exact role there is unclear. We hypothesized that PINK1 protects the heart against acute ischemia reperfusion injury (IRI by preventing mitochondrial dysfunction.Over-expressing PINK1 in HL-1 cardiac cells reduced cell death following simulated IRI (29.2±5.2% PINK1 versus 49.0±2.4% control; N = 320 cells/group P5 animals/group; P<0.05. Cardiomyocytes isolated from PINK1-/- hearts had a lower resting mitochondrial membrane potential, had inhibited mitochondrial respiration, generated more oxidative stress during simulated IRI, and underwent rigor contracture more rapidly in response to an uncoupler when compared to PINK1+/+ cells suggesting mitochondrial dysfunction in hearts deficient in PINK1.We show that the loss of PINK1 increases the heart's vulnerability to ischemia-reperfusion injury. This may be due, in part, to increased mitochondrial dysfunction. These findings implicate PINK1 as a novel target for cardioprotection.

Risk factors for hamstring injuries in male soccer players: a systematic review of prospective studies

NARCIS (Netherlands)

Beijsterveldt, A.M.C. van; Port, L.G.L. van de; Vereijken, A.J.; Backx, F.J.C.

2013-01-01

Hamstring injuries are common injuries in soccer players. In view of the high incidence and the serious consequences, identifying risk factors related to hamstring injuries is essential. The aim of this systematic review was therefore to identify risk factors for hamstring injuries in male adult

Mitochondrial dynamics in mammalian health and disease.

Science.gov (United States)

Liesa, Marc; Palacín, Manuel; Zorzano, Antonio

2009-07-01

The meaning of the word mitochondrion (from the Greek mitos, meaning thread, and chondros, grain) illustrates that the heterogeneity of mitochondrial morphology has been known since the first descriptions of this organelle. Such a heterogeneous morphology is explained by the dynamic nature of mitochondria. Mitochondrial dynamics is a concept that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial architecture (morphology and distribution), and connectivity mediated by tethering and fusion/fission events. The relevance of these events in mitochondrial and cell physiology has been partially unraveled after the identification of the genes responsible for mitochondrial fusion and fission. Furthermore, during the last decade, it has been identified that mutations in two mitochondrial fusion genes (MFN2 and OPA1) cause prevalent neurodegenerative diseases (Charcot-Marie Tooth type 2A and Kjer disease/autosomal dominant optic atrophy). In addition, other diseases such as type 2 diabetes or vascular proliferative disorders show impaired MFN2 expression. Altogether, these findings have established mitochondrial dynamics as a consolidated area in cellular physiology. Here we review the most significant findings in the field of mitochondrial dynamics in mammalian cells and their implication in human pathologies.

Acute kidney injury in symptomatic primary Epstein-Barr virus infectious mononucleosis: Systematic review.

Science.gov (United States)

Moretti, Milena; Lava, Sebastiano A G; Zgraggen, Lorenzo; Simonetti, Giacomo D; Kottanattu, Lisa; Bianchetti, Mario G; Milani, Gregorio P

2017-06-01

Textbooks and reviews do not mention the association of symptomatic primary Epstein-Barr virus infectious mononucleosis with acute kidney injury in subjects without immunodeficiency or autoimmunity. Stimulated by our experience with two cases, we performed a review of the literature. The literature documents 38 cases (26 male and 12 female individuals ranging in age from 0.3 to 51, median 18 years) of symptomatic primary Epstein-Barr virus infectious mononucleosis complicated by acute kidney injury: 27 acute interstitial nephritides, 1 jaundice-associated nephropathy, 7 myositides and 3 hemolytic uremic syndromes. Acute kidney injury requiring renal replacement therapy was observed in 18 (47%) cases. Acute kidney injury did not resolve in one patient with acute interstitial nephritis. Two patients died because of systemic complications. The remaining 35 cases fully recovered. In individuals with acute symptomatic Epstein-Barr virus infectious mononucleosis, a relevant kidney injury is rare but the outcome potentially fatal. It results from interstitial nephritis, myositis-associated acute kidney injury, hemolytic uremic syndrome or jaundice-associated nephropathy. Copyright © 2017 Elsevier B.V. All rights reserved.

Immersive virtual reality in traumatic brain injury rehabilitation: A literature review.

Science.gov (United States)

Aida, Jared; Chau, Brian; Dunn, Justin

2018-04-07

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the United States with its sequelae often affecting individuals long after the initial injury. Innovations in virtual reality (VR) technology may offer potential therapy options in the recovery from such injuries. However, there is currently no consensus regarding the efficacy of VR in the setting of TBI rehabilitation. The aim of this review is to evaluate and summarize the current literature regarding immersive VR in the rehabilitation of those with TBI. A comprehensive literature search was conducted utilizing PubMed, Google Scholar, and the Cochrane Review using the search terms "virtual reality," "traumatic brain injury," "brain injury," and "immersive." A total of 11 studies were evaluated. These were primarily of low-level evidence, with the exception of two randomized, controlled trials. 10 of 11 studies demonstrated improvement with VR therapy. VR was most frequently used to address gait or cognitive deficits. While the current literature generally offers support for the use of VR in TBI recovery, there is a paucity of strong evidence to support its widespread use. The increasing availability of immersive VR technology offers the potential for engaging therapy in TBI rehabilitation, but its utility remains uncertain given the limited studies available at this time.

Golf and upper limb injuries: a summary and review of the literature

Directory of Open Access Journals (Sweden)

Pollard Henry P

2005-05-01

Full Text Available Abstract Background Golf is a popular past time that provides exercise with social interaction. However, as with all sports and activities, injury may occur. Many golf-related injuries occur in the upper limb, yet little research on the potential mechanisms of these injuries has been conducted. Objective To review the current literature on golf-related upper limb injuries and report on potential causes of injury as it relates to the golf swing. Discussion An overview of the golf swing is described in terms of its potential to cause the frequently noted injuries. Most injuries occur at impact when the golf club hits the ball. This paper concludes that more research into golf-related upper limb injuries is required to develop a thorough understanding of how injuries occur. Types of research include epidemiology studies, kinematic swing analysis and electromyographic studies of the upper limb during golf. By conducting such research, preventative measures maybe developed to reduce golf related injury.

Inferior Alveolar Nerve Injury after Mandibular Third Molar Extraction: a Literature Review

Directory of Open Access Journals (Sweden)

Rafael Sarikov

2014-12-01

Full Text Available Objectives: The purpose of this study was to systematically review the comprehensive overview of literature data about injury to the inferior alveolar nerve after lower third molar extraction to discover the prevalence of injury, the risk factors, recovery rates, and alternative methods of treatment. Material and Methods: Literature was selected through a search of PubMed electronic databases. Articles from January 2009 to June 2014 were searched. English language articles with a minimum of 6 months patient follow-up and injury analysis by patient’s reporting, radiographic, and neurosensory testing were selected. Results: In total, 84 literature sources were reviewed, and 14 of the most relevant articles that are suitable to the criteria were selected. Articles were analyzed on men and women. The influence of lower third molar extraction (especially impacted on the inferior alveolar nerve was clearly seen. Conclusions: The incidence of injury to the inferior alveolar nerve after lower third molar extraction was about 0.35 - 8.4%. The injury of the inferior alveolar nerve can be predicted by various radiological signs. There are few risk factors that may increase the risk of injury to the nerve such as patients over the age of 24 years old, with horizontal impactions, and extraction by trainee surgeons. Recovery is preferable and permanent injury is very rare.

Injury of the Inferior Alveolar Nerve during Implant Placement: a Literature Review

Directory of Open Access Journals (Sweden)

Gintaras Juodzbalys

2011-01-01

Full Text Available Objectives: The purpose of present article was to review aetiological factors, mechanism, clinical symptoms, and diagnostic methods as well as to create treatment guidelines for the management of inferior alveolar nerve injury during dental implant placement.Material and Methods: Literature was selected through a search of PubMed, Embase and Cochrane electronic databases. The keywords used for search were inferior alveolar nerve injury, inferior alveolar nerve injuries, inferior alveolar nerve injury implant, inferior alveolar nerve damage, inferior alveolar nerve paresthesia and inferior alveolar nerve repair. The search was restricted to English language articles, published from 1972 to November 2010. Additionally, a manual search in the major anatomy, dental implant, periodontal and oral surgery journals and books were performed. The publications there selected by including clinical, human anatomy and physiology studies.Results: In total 136 literature sources were obtained and reviewed. Aetiological factors of inferior alveolar nerve injury, risk factors, mechanism, clinical sensory nerve examination methods, clinical symptoms and treatment were discussed. Guidelines were created to illustrate the methods used to prevent and manage inferior alveolar nerve injury before or after dental implant placement.Conclusions: The damage of inferior alveolar nerve during the dental implant placement can be a serious complication. Clinician should recognise and exclude aetiological factors leading to nerve injury. Proper presurgery planning, timely diagnosis and treatment are the key to avoid nerve sensory disturbances management.

Shoulder injuries attributed to resistance training: a brief review.

Science.gov (United States)

Kolber, Morey J; Beekhuizen, Kristina S; Cheng, Ming-Shun S; Hellman, Madeleine A

2010-06-01

The popularity of resistance training (RT) is evident by the more than 45 million Americans who engage in strength training regularly. Although the health and fitness benefits ascribed to RT are generally agreed upon, participation is not without risk. Acute and chronic injuries attributed to RT have been cited in the epidemiological literature among both competitive and recreational participants. The shoulder complex in particular has been alluded to as one of the most prevalent regions of injury. The purpose of this manuscript is to present an overview of documented shoulder injuries among the RT population and where possible discern mechanisms of injury and risk factors. A literature search was conducted in the PUBMED, CINAHL, SPORTDiscus, and OVID databases to identify relevant articles for inclusion using combinations of key words: resistance training, shoulder, bodybuilding, weightlifting, shoulder injury, and shoulder disorder. The results of the review indicated that up to 36% of documented RT-related injuries and disorders occur at the shoulder complex. Trends that increased the likelihood of injury were identified and inclusive of intrinsic risk factors such as joint and muscle imbalances and extrinsic risk factors, namely, that of improper attention to exercise technique. A majority of the available research was retrospective in nature, consisting of surveys and descriptive epidemiological reports. A paucity of research was available to identify predictive variables leading to injury, suggesting the need for future prospective-based investigations.

Targeting Mitochondrial Dysfunction with L-Alpha Glycerylphosphorylcholine.

Directory of Open Access Journals (Sweden)

Gerda Strifler

Full Text Available We hypothesized that L-alpha-glycerylphosphorylcholine (GPC, a deacylatedphosphatidylcholine derivative, can influence the mitochondrial respiratory activity and in this way, may exert tissue protective effects.Rat liver mitochondria were examined with high-resolution respirometry to analyze the effects of GPC on the electron transport chain in normoxic and anoxic conditions. Besides, Sprague-Dawley rats were subjected to sham operation or standardized liver ischemia-reperfusion (IR, with or without GPC administration. The reduced glutathione (GSH and oxidized glutathione disulfide (GSSG, the tissue myeloperoxidase, xanthine oxidoreductase and NADPH oxidases activities were measured. Tissue malondialdehyde and nitrite/nitrate formation, together with blood superoxide and hydrogen-peroxide production were assessed.GPC increased the efficacy of complex I-linked mitochondrial oxygen consumption, with significantly lower in vitro leak respiration. Mechanistically, liver IR injury was accompanied by deteriorated mitochondrial respiration and enhanced ROS production and, as a consequence, by significantly increased inflammatory enzyme activities. GPC administration decreased the inflammatory activation in line with the reduced oxidative and nitrosative stress markers.GPC, by preserving the mitochondrial complex I function respiration, reduced the biochemical signs of oxidative stress after an IR episode. This suggests that GPC is a mitochondria-targeted compound that indirectly suppresses the activity of major intracellular superoxide-generating enzymes.

Review of musculoskeletal injuries and prevention in the endoscopy practitioner.

Science.gov (United States)

Harvin, Glenn

2014-08-01

Practitioners of endoscopy often experience musculoskeletal pain and injury (most often in the back, neck, shoulders, hands, wrists, and thumbs) that are associated with the minute and repetitive strain that is placed on these areas during endoscopic procedures. This review of the current documentation of endoscopy-related pain and injuries among practitioners finds that such problems are widespread and specific in kind as well as strongly correlated with high procedure volume and procedure duration. Research on the nature and impact of cumulative trauma and overuse syndromes in other professions such as dentistry, pianists, production labor, and athletics is brought to bear on the work of the endoscopist. A more thorough understanding of the nature and prevalence of work-related pain and injury sustained by endoscopists should inform further development of ergonomic practices and equipment design. This article reviews current recommendations for ergonomic design in the endoscopy procedure space and finds that reported compliance with those recommendations is quite low. Strategies for the management of the risk of musculoskeletal injuries related to the practice of endoscopy include compliance with currently recommended ergonomic practices, education of trainees in ergonomic technique when practicing endoscopy, and research toward the modification and development of more ergonomic endoscopes and procedure spaces.

Injuries in runners; a systematic review on risk factors and sex differences

NARCIS (Netherlands)

Worp, M.P. van der; Haaf, D.S. Ten; Cingel, R. van; Wijer, A. de; Nijhuis-Van der Sanden, M.W.G.; Staal, J.B.

2015-01-01

BACKGROUND: The popularity of running continues to increase, which means that the incidence of running-related injuries will probably also continue to increase. Little is known about risk factors for running injuries and whether they are sex-specific. OBJECTIVES: The aim of this study was to review

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants.

Science.gov (United States)

Ten, Vadim S

2017-02-01

At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units-alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise.

Insulin Resistance and Mitochondrial Dysfunction.

Science.gov (United States)

Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

2017-01-01

Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.

Serum uric acid and acute kidney injury: A mini review

Directory of Open Access Journals (Sweden)

Kai Hahn

2017-09-01

Full Text Available Acute kidney injury causes great morbidity and mortality in both the community and hospital settings. Understanding the etiological factors and the pathophysiological principles resulting in acute kidney injury is essential in prompting appropriate therapies. Recently hyperuricemia has been recognized as a potentially modifiable risk factor for acute kidney injury, including that associated with cardiovascular surgery, radiocontrast administration, rhabdomyolysis, and associated with heat stress. This review discussed the evidence that repeated episodes of acute kidney injury from heat stress and dehydration may also underlie the pathogenesis of the chronic kidney disease epidemic that is occurring in Central America (Mesoamerican nephropathy. Potential mechanisms for how uric acid might contribute to acute kidney injury are also discussed, including systemic effects on renal microvasculature and hemodynamics, and local crystalline and noncrystalline effects on the renal tubules. Pilot clinical trials also show potential benefits of lowering uric acid on acute kidney injury associated with a variety of insults. In summary, there is mounting evidence that hyperuricemia may have a significant role in the development of acute kidney injury. Prospective, placebo controlled, randomized trials are needed to determine the potential benefit of uric acid lowering therapy on kidney and cardio-metabolic diseases.

E3 Ligase Subunit Fbxo15 and PINK1 Kinase Regulate Cardiolipin Synthase 1 Stability and Mitochondrial Function in Pneumonia

Directory of Open Access Journals (Sweden)

Bill B. Chen

2014-04-01

Full Text Available Acute lung injury (ALI is linked to mitochondrial injury, resulting in impaired cellular oxygen utilization; however, it is unknown how these events are linked on the molecular level. Cardiolipin, a mitochondrial-specific lipid, is generated by cardiolipin synthase (CLS1. Here, we show that S. aureus activates a ubiquitin E3 ligase component, Fbxo15, that is sufficient to mediate proteasomal degradation of CLS1 in epithelia, resulting in decreased cardiolipin availability and disrupted mitochondrial function. CLS1 is destabilized by the phosphatase and tensin homolog (PTEN-induced putative kinase 1 (PINK1, which binds CLS1 to phosphorylate and regulates CLS1 disposal. Like Fbxo15, PINK1 interacts with and regulates levels of CLS1 through a mechanism dependent upon Thr219. S. aureus infection upregulates this Fbxo15-PINK1 pathway to impair mitochondrial integrity, and Pink1 knockout mice are less prone to S. aureus-induced ALI. Thus, ALI-associated disruption of cellular bioenergetics involves bioeffectors that utilize a phosphodegron to elicit ubiquitin-mediated disposal of a key mitochondrial enzyme.

Cow-related trauma: a 10-year review of injuries admitted to a single institution.

LENUS (Irish Health Repository)

Murphy, Colin G

2012-02-01

INTRODUCTION: Bovine-related injuries to farmers are common in rural communities. Many injuries are significant requiring hospital admission and surgery. We reviewed all cattle-related injuries admitted to a regional trauma centre over 10 years and detail the nature of the injuries. METHOD: A retrospective review was undertaken, using hospital inpatient coding system (HIPE) to identify patients admitted following cow-related trauma for the last 10 years. From retrieved charts mechanism of injury was identified, demographics recorded and Injury Severity Score (ISS) and Trauma Injury Severity Score (TRISS) calculated based on the injuries sustained. RESULTS: 47 patients were identified, with a median age of 53 years. 4 injuries occurred in children, and 12 in patients over 65 years old. Three-quarters of those injured were male. Kicking was the most common mechanism of injury (n=21), but charge\\/head-butt injuries and trampling injuries were associated with more serious injury scores. 72% of patients were admitted under Orthopaedics as their primary care team, 25% under General Surgeons, with one patient admitted medically. Mean ISS score was 6.9 (range 1-50). 41 operative interventions were performed on 30 patients during their admission. 6.3% of patients required admission to Intensive Care with a mean length of stay of 12.3 days (range 2-21 days). There was no mortality. CONCLUSION: Cow-related trauma is a common among farming communities and is a potentially serious mechanism of injury that appears to be under-reported in a hospital context. Bovine-related head-butt and trampling injuries should be considered akin to high-velocity trauma.

The Role of Therapeutic Drugs on Acquired Mitochondrial Toxicity.

Science.gov (United States)

Morén, Constanza; Juárez-Flores, Diana Luz; Cardellach, Francesc; Garrabou, Glòria

2016-01-01

Certain therapeutic drugs used in medical practice may trigger mitochondrial toxicity leading to a wide range of clinical symptoms including deafness, neuropathy, myopathy, hyperlactatemia, lactic acidosis, pancreatitis and lipodystrophy, among others, which could even compromise the life of the patient. The aim of this work is to review the potential mitochondrial toxicity derived from drugs used in health care, including anesthetics, antiepileptics, neuroleptics, antidepressants, antivirals, antibiotics, antifungals, antimalarics, antineoplastics, antidiabetics, hypolipemiants, antiarrhythmics, anti-inflammatories and nitric oxide. We herein have reviewed data from experimental and clinical studies to document the molecular mitochondrial basis, potential biomarkers and putative clinical symptoms associated to secondary effects of drugs. One hundred and forty-five articles were selected and the information was organized by means of the primary target to which pharmacologic drugs were directed. Adverse toxic events were classified depending on the mitochondrial offtarget effect and whether they had been demonstrated in the experimental or clinical setting. Since treatment of acquired mitochondriopathies remains supportive and therapeutic interventions cannot be avoided, information of molecular and clinical consequences of toxic exposure becomes fundamental to assess riskbenefit imbalance of treatment prescription. Additionally, there is a crucial need to develop less mitochondrial toxic compounds, novel biomarkers to follow up mitochondrial toxicity (or implement those already proposed) and new approaches to prevent or revert unintended mitochondrial damage.

Anterior cruciate ligament injury/reinjury in alpine ski racing: a narrative review

Directory of Open Access Journals (Sweden)

Jordan MJ

2017-03-01

Full Text Available Matthew J Jordan,1 Per Aagaard,2 Walter Herzog1 1Human Performance Laboratory, The University of Calgary, Calgary, AB, Canada; 2Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster (SMRC, University of Southern Denmark, Odense M, Denmark Abstract: The purpose of the present review was to: 1 provide an overview of the current understanding on the epidemiology, etiology, risk factors, and prevention methods for anterior cruciate ligament (ACL injury in alpine ski racing; and 2 provide an overview of what is known pertaining to ACL reinjury and return to sport after ACL injury in alpine ski racing. Given that most of the scientific studies on ACL injuries in alpine ski racing have been descriptive, and that very few studies contributed higher level scientific evidence, a nonsystematic narrative review was employed. Three scholarly databases were searched for articles on ACL injury or knee injury in alpine ski racing. Studies were classified according to their relevance in relation to epidemiology, etiology, risk factors, and return to sport/reinjury prevention. Alpine ski racers (skiers were found to be at high risk for knee injuries, and ACL tears were the most frequent diagnosis. Three primary ACL injury mechanism were identified that involved tibial internal rotation and anteriorly directed shear forces from ski equipment and the environment. While trunk muscle strength imbalance and genetics were found to be predictive of ACL injuries in development-level skiers, there was limited scientific data on ACL injury risk factors among elite skiers. Based on expert opinion, research on injury risk factors should focus on equipment design, course settings/speed, and athlete factors (eg, fitness. While skiers seem to make a successful recovery following ACL injury, there may be persistent neuromuscular deficits. Future research efforts should be directed toward prospective studies on ACL injury/reinjury prevention in both

Therapeutic interventions for acute hamstring injuries: A systematic review

NARCIS (Netherlands)

G. Reurink (Gustaaf); G.J. Goudswaard (Gert Jan); J.L. Tol (Johannes); J.A.N. Verhaar (Jan); A. Weir (Adam); M.H. Moen (Maaike)

2012-01-01

textabstractBackground Despite the high rate of hamstring injuries, there is no consensus on their management, with a large number of different interventions being used. Recently several new injection therapies have been introduced. Objective To systematically review the literature on the

MPV17-related mitochondrial DNA maintenance defect: New cases and review of clinical, biochemical, and molecular aspects.

Science.gov (United States)

El-Hattab, Ayman W; Wang, Julia; Dai, Hongzheng; Almannai, Mohammed; Staufner, Christian; Alfadhel, Majid; Gambello, Michael J; Prasun, Pankaj; Raza, Saleem; Lyons, Hernando J; Afqi, Manal; Saleh, Mohammed A M; Faqeih, Eissa A; Alzaidan, Hamad I; Alshenqiti, Abduljabbar; Flore, Leigh Anne; Hertecant, Jozef; Sacharow, Stephanie; Barbouth, Deborah S; Murayama, Kei; Shah, Amit A; Lin, Henry C; Wong, Lee-Jun C

2018-04-01

Mitochondrial DNA (mtDNA) maintenance defects are a group of diseases caused by deficiency of proteins involved in mtDNA synthesis, mitochondrial nucleotide supply, or mitochondrial dynamics. One of the mtDNA maintenance proteins is MPV17, which is a mitochondrial inner membrane protein involved in importing deoxynucleotides into the mitochondria. In 2006, pathogenic variants in MPV17 were first reported to cause infantile-onset hepatocerebral mtDNA depletion syndrome and Navajo neurohepatopathy. To date, 75 individuals with MPV17-related mtDNA maintenance defect have been reported with 39 different MPV17 pathogenic variants. In this report, we present an additional 25 affected individuals with nine novel MPV17 pathogenic variants. We summarize the clinical features of all 100 affected individuals and review the total 48 MPV17 pathogenic variants. The vast majority of affected individuals presented with an early-onset encephalohepatopathic disease characterized by hepatic and neurological manifestations, failure to thrive, lactic acidemia, and mtDNA depletion detected mainly in liver tissue. Rarely, MPV17 deficiency can cause a late-onset neuromyopathic disease characterized by myopathy and peripheral neuropathy with no or minimal liver involvement. Approximately half of the MPV17 pathogenic variants are missense. A genotype with biallelic missense variants, in particular homozygous p.R50Q, p.P98L, and p.R41Q, can carry a relatively better prognosis. © 2017 Wiley Periodicals, Inc.

Interactive HIV-1 Tat and morphine-induced synaptodendritic injury is triggered through focal disruptions in Na⁺ influx, mitochondrial instability, and Ca²⁺ overload.

Science.gov (United States)

Fitting, Sylvia; Knapp, Pamela E; Zou, Shiping; Marks, William D; Bowers, M Scott; Akbarali, Hamid I; Hauser, Kurt F

2014-09-17

Synaptodendritic injury is thought to underlie HIV-associated neurocognitive disorders and contributes to exaggerated inflammation and cognitive impairment seen in opioid abusers with HIV-1. To examine events triggering combined transactivator of transcription (Tat)- and morphine-induced synaptodendritic injury systematically, striatal neuron imaging studies were conducted in vitro. These studies demonstrated nearly identical pathologic increases in dendritic varicosities as seen in Tat transgenic mice in vivo. Tat caused significant focal increases in intracellular sodium ([Na(+)]i) and calcium ([Ca(2+)]i) in dendrites that were accompanied by the emergence of dendritic varicosities. These effects were largely, but not entirely, attenuated by the NMDA and AMPA receptor antagonists MK-801 and CNQX, respectively. Concurrent morphine treatment accelerated Tat-induced focal varicosities, which were accompanied by localized increases in [Ca(2+)]i and exaggerated instability in mitochondrial inner membrane potential. Importantly, morphine's effects were prevented by the μ-opioid receptor antagonist CTAP and were not observed in neurons cultured from μ-opioid receptor knock-out mice. Combined Tat- and morphine-induced initial losses in ion homeostasis and increases in [Ca(2+)]i were attenuated by the ryanodine receptor inhibitor ryanodine, as well as pyruvate. In summary, Tat induced increases in [Na(+)]i, mitochondrial instability, excessive Ca(2+) influx through glutamatergic receptors, and swelling along dendrites. Morphine, acting via μ-opioid receptors, exacerbates these excitotoxic Tat effects at the same subcellular locations by mobilizing additional [Ca(2+)]i and by further disrupting [Ca(2+)]i homeostasis. We hypothesize that the spatiotemporal relationship of μ-opioid and aberrant AMPA/NMDA glutamate receptor signaling is critical in defining the location and degree to which opiates exacerbate the synaptodendritic injury commonly observed in neuro

A Multicenter Review of Superior Laryngeal Nerve Injury Following Anterior Cervical Spine Surgery.

Science.gov (United States)

Tempel, Zachary J; Smith, Justin S; Shaffrey, Christopher; Arnold, Paul M; Fehlings, Michael G; Mroz, Thomas E; Riew, K Daniel; Kanter, Adam S

2017-04-01

A retrospective multicenter case-series study; case report and review of the literature. The anatomy and function of the superior laryngeal nerve (SLN) are well described; however, the consequences of SLN injury remain variable and poorly defined. The prevalence of SLN injury as a consequence of cervical spine surgery is difficult to discern as its clinical manifestations are often inconstant and frequently of a subclinical degree. A multicenter study was performed to better delineate the risk factors, prevalence, and outcomes of SLN injury. A retrospective multicenter case-series study involving 21 high-volume surgical centers from the AO Spine North America Clinical Research Network. Medical records for 17 625 patients who received subaxial cervical spine surgery from 2005 to 2011 were reviewed to identify occurrence of 21 predefined treatment complications. Descriptive statistics were provided for baseline patient characteristics. A retrospective review of the neurosurgical literature on SLN injury was also performed. A total of 8887 patients who underwent anterior cervical spine surgery at the participating institutions were screened, and 1 case of SLN palsy was identified. The prevalence ranged from 0% to 1.25% across all centers. The patient identified underwent a C4 corpectomy. The SLN injury was identified after the patient demonstrated difficulty swallowing postoperatively. He underwent placement of a percutaneous gastrostomy tube and his SLN palsy resolved by 6 weeks. This multicenter study demonstrates that identification of SLN injury occurs very infrequently. Symptomatic SLN injury is an exceedingly rare complication of anterior cervical spine surgery. The SLN is particularly vulnerable when exposing the more rostral levels of the cervical spine. Careful dissection and retraction of the longus coli may decrease the risk of SLN injury during anterior cervical surgery.

Videogame-Related Illness and Injury: A Review of the Literature and Predictions for Pokémon GO!

Science.gov (United States)

Pourmand, Ali; Lombardi, Kevin; Kuhl, Evan; O'Connell, Francis

2017-02-01

Reports of videogame-related illness and injury soon emerged in the literature with the inception of videogame systems and subsequent development of novel gaming platforms and technologies. In an effort to better detail the impacts of these phenomena and provide recommendations for injury prevention as it relates to Pokémon Go and the larger world of augmented reality games, we conducted an extensive systems-based review of past trends in videogame-related illness and injury from the literature. A literature review using PubMed, Medline, and PsycInfo databases with search terms "Pokémon GO," "videogame injuries," "augmented reality injuries," and "Nintendo Injury" was performed. The search was limited to the English language, and the Boolean were used to combine the search terms. The literature search yielded 359 peer-reviewed articles, 44 of which met the study criteria and included in the review. Seventeen additional popular press reports detailing injuries related to Pokémon Go were also incorporated. Videogame-related injuries and illness include both physical trauma as well as psychological and behavioral disorder with unique patterns of injury and illness linked to specific gaming platforms. As videogames become increasingly advanced and immersive, they expose players to unique and often more serious injury and illness. Augmented reality games, such as Pokémon GO, are the next step in the evolution of this trend and likely portend a future in which many pathologic processes may become increasingly common.

Therapeutic interventions for acute hamstring injuries: a systematic review

NARCIS (Netherlands)

Reurink, Gustaaf; Goudswaard, Gert Jan; Tol, Johannes L.; Verhaar, Jan A. N.; Weir, Adam; Moen, Maarten H.

2012-01-01

Despite the high rate of hamstring injuries, there is no consensus on their management, with a large number of different interventions being used. Recently several new injection therapies have been introduced. To systematically review the literature on the effectiveness of therapeutic interventions

The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

Directory of Open Access Journals (Sweden)

Yajin Liao

2017-02-01

Full Text Available The mitochondrial calcium uniporter (MCU—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP; however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders.

Mitochondrial morphology transitions and functions: implications for retrograde signaling?

Science.gov (United States)

Picard, Martin; Shirihai, Orian S.; Gentil, Benoit J.

2013-01-01

In response to cellular and environmental stresses, mitochondria undergo morphology transitions regulated by dynamic processes of membrane fusion and fission. These events of mitochondrial dynamics are central regulators of cellular activity, but the mechanisms linking mitochondrial shape to cell function remain unclear. One possibility evaluated in this review is that mitochondrial morphological transitions (from elongated to fragmented, and vice-versa) directly modify canonical aspects of the organelle's function, including susceptibility to mitochondrial permeability transition, respiratory properties of the electron transport chain, and reactive oxygen species production. Because outputs derived from mitochondrial metabolism are linked to defined cellular signaling pathways, fusion/fission morphology transitions could regulate mitochondrial function and retrograde signaling. This is hypothesized to provide a dynamic interface between the cell, its genome, and the fluctuating metabolic environment. PMID:23364527

Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes

International Nuclear Information System (INIS)

Liu, Cong; Sekine, Shuichi; Ito, Kousei

2016-01-01

Evidence that mitochondrial dysfunction plays a central role in drug-induced liver injury is rapidly accumulating. In contrast to physiological conditions, in which almost all adenosine triphosphate (ATP) in hepatocytes is generated in mitochondria via aerobic respiration, the high glucose content and limited oxygen supply of conventional culture systems force primary hepatocytes to generate most ATP via cytosolic glycolysis. Thus, such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, and are not suitable to identify drugs with mitochondrial liabilities. In this study, primary rat hepatocytes were cultured in galactose-based medium, instead of the conventional glucose-based medium, and in hyperoxia to improve the reliance of energy generation on aerobic respiration. Activation of mitochondria was verified by diminished cellular lactate release and increased oxygen consumption. These conditions improved sensitivity to the mitochondrial complex I inhibitor rotenone. Since oxidative stress is also a general cause of mitochondrial impairment, cells were exposed to test compounds in the presence of transferrin to increase the generation of reactive oxygen species via increased uptake of iron. Finally, 14 compounds with reported mitochondrial liabilities were tested to validate this new drug-induced mitochondrial toxicity assay. Overall, the culture of primary rat hepatocytes in galactose, hyperoxia and transferrin is a useful model for the identification of mitochondrial dysfunction-related drug-induced hepatotoxicity. - Highlights: • Drug-induced mitochondrial toxicity was evaluated using primary rat hepatocytes. • Galactose and hyperoxia could activate OXPHOS in primary rat hepatocytes. • Cells with enhanced OXPHOS exhibit improved sensitivity to mitochondrial toxins. • Transferrin potentiate mitochondrial toxicity via increased ROS production.

Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes

Energy Technology Data Exchange (ETDEWEB)

Liu, Cong; Sekine, Shuichi, E-mail: ssekine@faculty.chiba-u.jp; Ito, Kousei

2016-07-01

Evidence that mitochondrial dysfunction plays a central role in drug-induced liver injury is rapidly accumulating. In contrast to physiological conditions, in which almost all adenosine triphosphate (ATP) in hepatocytes is generated in mitochondria via aerobic respiration, the high glucose content and limited oxygen supply of conventional culture systems force primary hepatocytes to generate most ATP via cytosolic glycolysis. Thus, such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, and are not suitable to identify drugs with mitochondrial liabilities. In this study, primary rat hepatocytes were cultured in galactose-based medium, instead of the conventional glucose-based medium, and in hyperoxia to improve the reliance of energy generation on aerobic respiration. Activation of mitochondria was verified by diminished cellular lactate release and increased oxygen consumption. These conditions improved sensitivity to the mitochondrial complex I inhibitor rotenone. Since oxidative stress is also a general cause of mitochondrial impairment, cells were exposed to test compounds in the presence of transferrin to increase the generation of reactive oxygen species via increased uptake of iron. Finally, 14 compounds with reported mitochondrial liabilities were tested to validate this new drug-induced mitochondrial toxicity assay. Overall, the culture of primary rat hepatocytes in galactose, hyperoxia and transferrin is a useful model for the identification of mitochondrial dysfunction-related drug-induced hepatotoxicity. - Highlights: • Drug-induced mitochondrial toxicity was evaluated using primary rat hepatocytes. • Galactose and hyperoxia could activate OXPHOS in primary rat hepatocytes. • Cells with enhanced OXPHOS exhibit improved sensitivity to mitochondrial toxins. • Transferrin potentiate mitochondrial toxicity via increased ROS production.

The "sequence of prevention" for musculoskeletal injuries among adult recreational footballers: A systematic review of the scientific literature.

Science.gov (United States)

Kilic, Ozgur; Kemler, Ellen; Gouttebarge, Vincent

2018-02-02

To gather epidemiological information related to all steps of Van Mechelen's "sequence of prevention" for musculoskeletal injuries among adult recreational football players. A systematic review of the scientific literature was conducted in Medline via Pubmed. Therefore, two highly sensitive search strategies based on three groups of keywords (and related search terms) were used. In total, 33 relevant original studies were included in our systematic review. The results of our systematic review showed that the incidence of musculoskeletal injuries among recreational adult football players ranged from 9.6 to 15.8 injuries per 1000 exposure hours. These injuries are especially located in the ankle, knee, groin and hamstring, being associated with previous injury and match exposure. The FIFA11 + injury prevention programme and the Nordic Hamstring Exercise (NHE) were found to be effective for the reduction or prevention of musculoskeletal injuries among adult recreational football players. Our systematic review showed that musculoskeletal injuries are common among recreational adult football players, while effective preventive programmes are available. Further studies should focus on the identification and understanding of the key factors responsible for the optimal adoption, implementation and maintenance of these measures. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mitochondrial Dysfunction: Different Routes to Alzheimer’s Disease Therapy

Directory of Open Access Journals (Sweden)

Pasquale Picone

2014-01-01

Full Text Available Mitochondria are dynamic ATP-generating organelle which contribute to many cellular functions including bioenergetics processes, intracellular calcium regulation, alteration of reduction-oxidation potential of cells, free radical scavenging, and activation of caspase mediated cell death. Mitochondrial functions can be negatively affected by amyloid β peptide (Aβ, an important component in Alzheimer’s disease (AD pathogenesis, and Aβ can interact with mitochondria and cause mitochondrial dysfunction. One of the most accepted hypotheses for AD onset implicates that mitochondrial dysfunction and oxidative stress are one of the primary events in the insurgence of the pathology. Here, we examine structural and functional mitochondrial changes in presence of Aβ. In particular we review data concerning Aβ import into mitochondrion and its involvement in mitochondrial oxidative stress, bioenergetics, biogenesis, trafficking, mitochondrial permeability transition pore (mPTP formation, and mitochondrial protein interaction. Moreover, the development of AD therapy targeting mitochondria is also discussed.

77 FR 28392 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Science.gov (United States)

2012-05-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Alcohol-related Motor Vehicle Injury Research, FOA CE12-006, initial review. In...

Reporting Multiple Individual Injuries in Studies of Team Ball Sports: A Systematic Review of Current Practice

OpenAIRE

Fortington, Lauren V; van der Worp, Henk; van den Akker-Scheek, Inge; Finch, Caroline F

2017-01-01

Background To identify and prioritise targets for injury prevention efforts, injury incidence studies are widely reported. The accuracy and consistency in calculation and reporting of injury incidence is crucial. Many individuals experience more than one injury but multiple injuries are not consistently reported in sport injury incidence studies. Objective The aim of this systematic review was to evaluate current practice of how multiple injuries within individuals have been defined and repor...

Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats.

Directory of Open Access Journals (Sweden)

Jun Li

Full Text Available BACKGROUND AND PURPOSE: Mitochondrial dysfunction has been implicated in the cell death observed after cerebral ischemia, and several mechanisms for this dysfunction have been proposed. Reperfusion after transient cerebral ischemia may cause continued and even more severe damage to the brain. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. The purpose of this study was to observe the features of mitochondrial dysfunction in isolated mitochondria during the reperfusion period following focal cerebral ischemia. METHODS: Male Wistar rats were subjected to focal cerebral ischemia. Mitochondria were isolated using Percoll density gradient centrifugation. The isolated mitochondria were fixed for electron microscopic examination; calcium-induced mitochondrial swelling was quantified using spectrophotometry. Cyclophilin D was detected by Western blotting. Fluorescent probes were used to selectively stain mitochondria to measure their membrane potential and to measure reactive oxidative species production using flow cytometric analysis. RESULTS: Signs of damage were observed in the mitochondrial morphology after exposure to reperfusion. The mitochondrial swelling induced by Ca(2+ increased gradually with the increasing calcium concentration, and this tendency was exacerbated as the reperfusion time was extended. Cyclophilin D protein expression peaked after 24 hours of reperfusion. The mitochondrial membrane potential was decreased significantly during the reperfusion period, with the greatest decrease observed after 24 hours of reperfusion. The surge in mitochondrial reactive oxidative species occurred after 2 hours of reperfusion and was maintained at a high level during the reperfusion period. CONCLUSIONS: Reperfusion following focal cerebral ischemia induced significant mitochondrial morphological damage and Ca(2+-induced mitochondrial swelling. The mechanism of this swelling may be mediated by

Iatrogenic splenic injury: review of the literature and medico-legal issues

Directory of Open Access Journals (Sweden)

Feola Alessandro

2016-01-01

Full Text Available Iatrogenic splenic injury is a recognized complication in abdominal surgery. The aim of this paper is to understand the medico-legal issues of iatrogenic splenic injuries. We performed a literature review on PubMed and Scopus using iatrogenic splenic or spleen injury and iatrogenic splenic rupture as keywords. Iatrogenic splenic injury cases were identified. Most cases were related to colonoscopy, but we also identified cases related to upper gastrointestinal procedures, colonic surgery, ERCP, left nephrectomy and/or adrenalectomy, percutaneous nephrolithotomy, vascular operations involving the abdominal aorta, gynecological operation, left lung biopsy, chest drain, very rarely spinal surgery and even cardiopulmonary resuscitation. There are several surgical procedures that can lead to a splenic injury. However, from a medico-legal point of view, it is important to assess whether the cause can be attributed to a technical error of the operator rather than being an unpredictable and unpreventable complication. It is important for the medico-legal expert to have great knowledge on iatrogenic splenic injuries because it is important to evaluate every step of the first procedure performed, how a splenic injury is produced, and whether the correct treatment for the splenic injury was administered in a judgment.

Lateral ankle injury. Literature review and report of two cases.

Science.gov (United States)

Pollard, Henry; Sim, Patrick; McHardy, Andrew

2002-07-01

Injury to the ankle joint is the most common peripheral joint injury. The sports that most commonly produce high ankle injury rates in their participating athletes include: basketball, netball, and the various codes of football. To provide an up to date understanding of manual therapy relevant to lateral ligament injury of the ankle. A discussion of the types of ligament injury and common complicating factors that present with lateral ankle pain is presented along with a review of relevant anatomy, assessment and treatment. Also included is a discussion of the efficacy of manual therapy in the treatment of ankle sprain. A detailed knowledge of the anatomy of the ankle as well as the early recognition of factors that may delay the rate of healing are important considerations when developing a management plan for inversion sprains of the ankle. This area appears to be under-researched however it was found that movement therapy and its various forms appear to be the most efficient and most effective method of treating uncomplicated ankle injury. Future investigations should involve a study to determine the effect chiropractic treatment (manipulation) may have on the injured ankle.

Incidence, aetiology and prevention of musculoskeletal injuries in volleyball: A systematic review of the literature.

Science.gov (United States)

Kilic, O; Maas, M; Verhagen, E; Zwerver, J; Gouttebarge, V

2017-07-01

Currently, there is no overview of the incidence and (volleyball-specific) risk factors of musculoskeletal injuries among volleyball players, nor any insight into the effect of preventive measures on the incidence of injuries in volleyball. This study aimed to review systematically the scientific evidence on the incidence, prevalence, aetiology and preventive measures of volleyball injuries. To this end, a highly sensitive search strategy was built based on two groups of keywords (and their synonyms). Two electronic databases were searched, namely Medline (biomedical literature) via Pubmed, and SPORTDiscus (sports and sports medicine literature) via EBSCOhost. The results showed that ankle, knee and shoulder injuries are the most common injuries sustained while playing volleyball. Results are presented separately for acute and overuse injuries, as well as for contact and non-contact injuries. Measures to prevent musculoskeletal injuries, anterior knee injuries and ankle injuries were identified in the scientific literature. These preventive measures were found to have a significant effect on decreasing the occurrence of volleyball injuries (for instance on ankle injuries with a reduction from 0.9 to 0.5 injuries per 1000 player hours). Our systematic review showed that musculoskeletal injuries are common among volleyball players, while effective preventive measures remain scarce. Further epidemiological studies should focus on other specific injuries besides knee and ankle injuries, and should also report their prevalence and not only the incidence. Additionally, high-quality studies on the aetiology and prevention of shoulder injuries are lacking and should be a focus of future studies.

Improvement of mitochondrial function and dynamics by the metabolic enhancer piracetam.

Science.gov (United States)

Stockburger, Carola; Kurz, Christopher; Koch, Konrad A; Eckert, Schamim H; Leuner, Kristina; Müller, Walter E

2013-10-01

The metabolic enhancer piracetam is used in many countries to treat cognitive impairment in aging, brain injuries, as well as dementia such as AD (Alzheimer's disease). As a specific feature of piracetam, beneficial effects are usually associated with mitochondrial dysfunction. In previous studies we were able to show that piracetam enhanced ATP production, mitochondrial membrane potential as well as neurite outgrowth in cell and animal models for aging and AD. To investigate further the effects of piracetam on mitochondrial function, especially mitochondrial fission and fusion events, we decided to assess mitochondrial morphology. Human neuroblastoma cells were treated with the drug under normal conditions and under conditions imitating aging and the occurrence of ROS (reactive oxygen species) as well as in stably transfected cells with the human wild-type APP (amyloid precursor protein) gene. This AD model is characterized by expressing only 2-fold more human Aβ (amyloid β-peptide) compared with control cells and therefore representing very early stages of AD when Aβ levels gradually increase over decades. Interestingly, these cells exhibit an impaired mitochondrial function and morphology under baseline conditions. Piracetam is able to restore this impairment and shifts mitochondrial morphology back to elongated forms, whereas there is no effect in control cells. After addition of a complex I inhibitor, mitochondrial morphology is distinctly shifted to punctate forms in both cell lines. Under these conditions piracetam is able to ameliorate morphology in cells suffering from the mild Aβ load, as well as mitochondrial dynamics in control cells.

Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic.

Science.gov (United States)

Ortega-Domínguez, Bibiana; Aparicio-Trejo, Omar Emiliano; García-Arroyo, Fernando E; León-Contreras, Juan Carlos; Tapia, Edilia; Molina-Jijón, Eduardo; Hernández-Pando, Rogelio; Sánchez-Lozada, Laura Gabriela; Barrera-Oviedo, Diana; Pedraza-Chaverri, José

2017-09-01

Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model. It was found that curcumin prevents cisplatin-induced: (a) AKI and (b) alterations in the following mitochondrial parameters: bioenergetics, ultrastructure, hydrogen peroxide production and dynamic. In fact, curcumin prevented the increase of mitochondrial fission 1 protein (FIS1), the decrease of optic atrophy 1 protein (OPA1) and the decrease of NAD + -dependent deacetylase sirtuin-3 (SIRT3), a mitochondrial dynamic regulator as well as the increase in the mitophagy associated proteins parkin and phosphatase and tensin homologue (PTEN)-induced putative kinase protein 1 (PINK1). In conclusion, the protective effect of curcumin in cisplatin-induced AKI was associated with the prevention of the alterations in mitochondrial bioenergetics, ultrastructure, redox balance, dynamic, and SIRT3 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Amateur boxing and risk of chronic traumatic brain injury: systematic review of observational studies.

Science.gov (United States)

Loosemore, Mike; Knowles, Charles H; Whyte, Greg P

2007-10-20

To evaluate the risk of chronic traumatic brain injury from amateur boxing. Secondary research performed by combination of sport physicians and clinical academics. DESIGN, DATA SOURCES, AND METHODS: Systematic review of observational studies in which chronic traumatic brain injury was defined as any abnormality on clinical neurological examination, psychometric testing, neuroimaging studies, and electroencephalography. Studies were identified through database (1950 to date) and bibliographic searches without language restrictions. Two reviewers extracted study characteristics, quality, and data, with adherence to a protocol developed from a widely recommended method for systematic review of observational studies (MOOSE). 36 papers had relevant extractable data (from a detailed evaluation of 93 studies of 943 identified from the initial search). Quality of evidence was generally poor. The best quality studies were those with a cohort design and those that used psychometric tests. These yielded the most negative results: only four of 17 (24%) better quality studies found any indication of chronic traumatic brain injury in a minority of boxers studied. There is no strong evidence to associate chronic traumatic brain injury with amateur boxing.

Isoflurane anesthesia initiated at the onset of reperfusion attenuates oxidative and hypoxic-ischemic brain injury.

Directory of Open Access Journals (Sweden)

Sergey A Sosunov

Full Text Available This study demonstrates that in mice subjected to hypoxia-ischemia (HI brain injury isoflurane anesthesia initiated upon reperfusion limits a release of mitochondrial oxidative radicals by inhibiting a recovery of complex-I dependent mitochondrial respiration. This significantly attenuates an oxidative stress and reduces the extent of HI brain injury. Neonatal mice were subjected to HI, and at the initiation of reperfusion were exposed to isoflurane with or without mechanical ventilation. At the end of HI and isoflurane exposure cerebral mitochondrial respiration, H2O2 emission rates were measured followed by an assessment of cerebral oxidative damage and infarct volumes. At 8 weeks after HI navigational memory and brain atrophy were assessed. In vitro, direct effect of isoflurane on mitochondrial H2O2 emission was compared to that of complex-I inhibitor, rotenone. Compared to controls, 15 minutes of isoflurane anesthesia inhibited recovery of the compex I-dependent mitochondrial respiration and decreased H2O2 production in mitochondria supported with succinate. This was associated with reduced oxidative brain injury, superior navigational memory and decreased cerebral atrophy compared to the vehicle-treated HI-mice. Extended isoflurane anesthesia was associated with sluggish recovery of cerebral blood flow (CBF and the neuroprotection was lost. However, when isoflurane anesthesia was supported with mechanical ventilation the CBF recovery improved, the event associated with further reduction of infarct volume compared to HI-mice exposed to isoflurane without respiratory support. Thus, in neonatal mice brief isoflurane anesthesia initiated at the onset of reperfusion limits mitochondrial release of oxidative radicals and attenuates an oxidative stress. This novel mechanism contributes to neuroprotective action of isoflurane. The use of mechanical ventilation during isoflurane anesthesia counterbalances negative effect of isoflurane anesthesia on

Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease

Directory of Open Access Journals (Sweden)

Isaac G Onyango

2018-01-01

Full Text Available Alzheimer's disease (AD is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.

Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

DEFF Research Database (Denmark)

Larsen, Steen; Díez-Sánchez, Carmen; Rabøl, Rasmus

2014-01-01

and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30......% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present....

17β-Estradiol prevents cell death and mitochondrial dysfunction by an estrogen receptor-dependent mechanism in astrocytes after oxygen-glucose deprivation/reperfusion.

Science.gov (United States)

Guo, Jiabin; Duckles, Sue P; Weiss, John H; Li, Xuejun; Krause, Diana N

17β-Estradiol (E2) has been shown to protect against ischemic brain injury, yet its targets and the mechanisms are unclear. E2 may exert multiple regulatory actions on astrocytes that may greatly contribute to its ability to protect the brain. Mitochondria are recognized as playing central roles in the development of injury during ischemia. Increasing evidence indicates that mitochondrial mechanisms are critically involved in E2-mediated protection. In this study, the effects of E2 and the role of mitochondria were evaluated in primary cultures of astrocytes subjected to an ischemia-like condition of oxygen-glucose deprivation (OGD)/reperfusion. We showed that E2 treatment significantly protects against OGD/reperfusion-induced cell death as determined by cell viability, apoptosis, and lactate dehydrogenase leakage. The protective effects of E2 on astrocytic survival were blocked by an estrogen receptor (ER) antagonist (ICI-182,780) and were mimicked by an ER agonist selective for ERα (PPT), but not by an ER agonist selective for ERβ (DPN). OGD/reperfusion provoked mitochondrial dysfunction as manifested by an increase in cellular reactive oxygen species production, loss of mitochondrial membrane potential, and depletion of ATP. E2 pretreatment significantly inhibited OGD/reperfusion-induced mitochondrial dysfunction, and this effect was also blocked by ICI-182,780. Therefore, we conclude that E2 provides direct protection to astrocytes from ischemic injury by an ER-dependent mechanism, highlighting an important role for ERα. Estrogen protects against mitochondrial dysfunction at the early phase of ischemic injury. However, overall implications for protection against brain ischemia and its complex sequelae await further exploration. Copyright © 2012 Elsevier Inc. All rights reserved.

Guarding the precious smile: incidence and prevention of injury in sports: a review.

Science.gov (United States)

Dhillon, Bikramjit Singh; Sood, Nikhil; Sood, Niti; Sah, Nupur; Arora, Dhruv; Mahendra, Ashish

2014-07-01

The paper provides a review about the orofacial injuries sustained during sports and the options available to the athletes for their prevention. It was done with a purpose to determine three different aspects incidence of dental injury during sporting activities, role of mouthguards in preventing sports injury, types of mouthguards and their properties. From this review, it is clear that sports carry a considerable risk of injury, this is not only true for the contact sports such as rugby or kickboxing, but also for seemingly less dangerous sports such as football. Amongst the different types of mouthguards, the most acceptable and safe ones are the custom-fabricated mouthguards, in particular the pressure-laminated ones. In general, mouthguard usage is less than the dental profession would recommend. As much of progress has been made in this area, need for the use of mouthguard needs to be emphasized and promoted by the dental profession.

Return to Play After Hamstring Injuries: A Qualitative Systematic Review of Definitions and Criteria.

Science.gov (United States)

van der Horst, Nick; van de Hoef, Sander; Reurink, Gustaaf; Huisstede, Bionka; Backx, Frank

2016-06-01

More than half of the recurrent hamstring injuries occur within the first month after return-to-play (RTP). Although there are numerous studies on RTP, comparisons are hampered by the numerous definitions of RTP used. Moreover, there is no consensus on the criteria used to determine when a person can start playing again. These criteria need to be critically evaluated, in an attempt to reduce recurrence rates and optimize RTP. To carry out a systematic review of the literature on (1) definitions of RTP used in hamstring research and (2) criteria for RTP after hamstring injuries. Systematic review. Seven databases (PubMed, EMBASE/MEDLINE, CINAHL, PEDro, Cochrane, SPORTDiscus, Scopus) were searched for articles that provided a definition of, or criteria for, RTP after hamstring injury. There were no limitations on the methodological design or quality of articles. Content analysis was used to record and analyze definitions and criteria for RTP after hamstring injury. Twenty-five papers fulfilled inclusion criteria, of which 13 provided a definition of RTP and 23 described criteria to support the RTP decision. "Reaching the athlete's pre-injury level" and "being able to perform full sport activities" were the primary content categories used to define RTP. "Absence of pain", "similar strength", "similar flexibility", "medical staff clearance", and "functional performance" were core themes to describe criteria to support the RTP decision after hamstring injury. Only half of the included studies provided some definition of RTP after hamstring injury, of which reaching the athlete's pre-injury level and being able to perform full sport activities were the most important. A wide variety of criteria are used to support the RTP decision, none of which have been validated. More research is needed to reach a consensus on the definition of RTP and to provide validated RTP criteria to facilitate hamstring injury management and reduce hamstring injury recurrence. PROSPERO

Unintentional injury prevention and the role of occupational therapy in the Solomon Islands: an integrative review.

Science.gov (United States)

Daufanamae, Barbara U; Franklin, Richard C; Eagers, Jackie

2016-01-01

Unintentional injuries (injuries for which there is no evidence of a predetermined intent) are one of the leading causes of death worldwide, particularly in low- and middle-income countries (LMICs). Although evidence demonstrates unintentional injuries are preventable it is a public health challenge for many LMICs such as the Solomon Islands. Occupational therapists are well placed to contribute to injury prevention, as they have specialised skills to analyse the accessibility and safety of the environments within which people conduct their daily occupations. While the role of occupational therapy in unintentional injury prevention is well known in high-income countries, it is unfamiliar in LMICs, especially in the Solomon Islands. This integrative review aimed to explore the incidence of common unintentional injuries, and the burden in the Solomon Islands; and explore the potential role of occupational therapy in unintentional injury prevention in the Solomon Islands, based on current activities in LMICs. Articles were reviewed from six databases (Medline, CINAHL, OTDBase, OT Seeker, Scopus and PsychInfo). Five articles met the inclusion criteria for the first objective and 15 articles met the inclusion criteria for the second objective. These articles were thematically analysed where themes and codes associated with the research objectives were extracted and analysed. Unintentional injuries in the Solomon Islands reported in the literature included ocular trauma, falls from fruit trees and coconut palms, and road traffic crashes. Burden of injury reported was mostly associated with loss of productivity. Occupational therapists undertook rehabilitative, biomechanical, neurodevelopmental and educational roles in LMIC, focusing on tertiary and secondary injury prevention. This integrative review suggests that there is limited information regarding injury in the Solomon Islands. However, evidence is available in LMICs to suggest that occupational therapy services can

Occupational injury among migrant workers in China: a systematic review

Science.gov (United States)

Fitzgerald, Simon; Chen, Xin; Qu, Hui; Sheff, Mira Grice

2017-01-01

Objectives This review considers the state of occupational injury surveillance and prevention among migrant workers in China and suggests areas of focus for future research on the topic. Methods Bibliographic databases were searched for qualitative and quantitative studies on surveillance of and interventions to prevent occupational injury among migrant workers in mainland China. Additional abstracts were identified from the citations of relevant articles from the database search. Studies fitting the inclusion criteria were evaluated, and findings were extracted and summarised. Results The search uncovered 726 studies in the English-language databases searched, and 3109 in the Chinese database. This article analyses a total of 19 research articles that fit the inclusion criteria with qualitative or quantitative data on occupational injury surveillance and prevention of migrant workers in China. Despite evidence of the vulnerability of migrant workers in the workplace, there is little systematic surveillance of occupational injury and few evaluated interventions. Conclusions Migrant workers account for a disproportionate burden of occupational injury morbidity and mortality in China. However, data are inconsistent and inadequate to detail injury incidence or to evaluate interventions. The following are suggestions to decrease injury incidence among migrants: strengthen the national system of occupational injury surveillance; focus surveillance and interventions on high-risk occupations employing migrants such as construction, manufacturing and small mining operations; improve occupational safety training and access to appropriate safety equipment; evaluate recent changes in occupational health and safety and evaluate outcome of multi-party interventions to reduce occupational injury among migrant workers. PMID:23710065

Musculoskeletal injuries and pain in dancers: a systematic review update.

Science.gov (United States)

Jacobs, Craig L; Hincapié, Cesar A; Cassidy, J David

2012-01-01

The objective of this study was to assemble and synthesize the best available literature from 2004 to 2008 on musculoskeletal injury and pain in dancers. MEDLINE and CINAHL were the primary sources of data. Indexed terms such as dance, dancer, dancing, athletic injuries, occupational injuries, sprains and strains, musculoskeletal diseases, bone density, menstruation disturbances, and eating disorders were used to search the databases. Citations were screened for relevance using a priori criteria, and relevant studies were critically reviewed for scientific merit by the best-evidence synthesis method. After screening, 19 articles were found to be scientifically admissible. Data from accepted studies were abstracted into evidence tables relating to: prevalence and associated factors; incidence and risk factors; intervention; and injury characteristics and prognosis of musculoskeletal injury and pain in dancers. Principal findings included: a high prevalence and incidence of lower extremity, hip and back injuries; preliminary evidence that psychosocial and psychological issues such as stress and coping strategies affect injury frequency and duration; history of a previous lateral ankle sprain is associated with an increased risk of ankle sprain in the contralateral ankle in dance students; fatigue may play a role in ACL injury in dancers; acute hamstring strains in dancers affect tendon more than muscle tissue, often resulting in prolonged absence from dance. It is concluded that, while there are positive developments in the literature on the epidemiology, diagnosis, prognosis, treatment, and prevention of MSK injuries and pain in dancers, much room for improvement remains. Suggestions for future research are offered.

Redox Regulation of Mitochondrial Function

Science.gov (United States)

Handy, Diane E.

2012-01-01

Abstract Redox-dependent processes influence most cellular functions, such as differentiation, proliferation, and apoptosis. Mitochondria are at the center of these processes, as mitochondria both generate reactive oxygen species (ROS) that drive redox-sensitive events and respond to ROS-mediated changes in the cellular redox state. In this review, we examine the regulation of cellular ROS, their modes of production and removal, and the redox-sensitive targets that are modified by their flux. In particular, we focus on the actions of redox-sensitive targets that alter mitochondrial function and the role of these redox modifications on metabolism, mitochondrial biogenesis, receptor-mediated signaling, and apoptotic pathways. We also consider the role of mitochondria in modulating these pathways, and discuss how redox-dependent events may contribute to pathobiology by altering mitochondrial function. Antioxid. Redox Signal. 16, 1323–1367. PMID:22146081

Mitochondrial Myopathy: A Rare Cause of Early-Onset Vocal Fold Atrophy

Science.gov (United States)

Kelly, Elizabeth A.; Bock, Jonathan M.; Peltier, Amanda C.; Oh, Shin J.; Garrett, C. Gaelyn

2014-01-01

Objectives We present the second published case of laryngeal involvement in mitochondrial myopathy. Methods A patient with laryngeal involvement of mitochondrial myopathy is presented, together with a literature review. Results A 41-year-old man presented with progressive breathy dysphonia. His brother had mitochondrial myopathy. Biopsy of the biceps muscle demonstrated cytochrome C oxidase–negative ragged blue fibers confirming mitochondrial myopathy. Videostroboscopy showed marked vocal fold atrophy, but subsequent injection laryngoplasty did not significantly improve the patient’s voice, despite improved postoperative glottic closure. Conclusions Mitochondrial myopathy should be considered in the differential diagnosis of severe early-onset vocal fold atrophy. PMID:23577570

Liver Injury from Herbal, Dietary, and Weight Loss Supplements: a Review

Science.gov (United States)

Zheng, Elizabeth X.; Navarro, Victor J.

2015-01-01

Herbal and dietary supplement usage has increased steadily over the past several years in the United States. Among the non-bodybuilding herbal and dietary supplements, weight loss supplements were among the most common type of HDS implicated in liver injury. While drug induced liver injury is rare, its consequences are significant and on the rise. The purpose of this review is to highlight case reports of weight loss products such as Hydroxycut and OxyElite Pro as one form of HDS that have hepatotoxic potential and to characterize its clinical effects as well as pattern of liver injury. We also propose future strategies in the identification and study of potentially hepatotoxic compounds in an effort to outline a diagnostic approach for identifying any drug induced liver injury. PMID:26357638

Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection

OpenAIRE

Mukherjee, Uma A.; Ong, Sang-Bing; Ong, Sang-Ging; Hausenloy, Derek J.

2015-01-01

Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia/reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotect...

Elastic Bandaging for Orthopedic- and Sports-Injury Prevention and Rehabilitation: A Systematic Review.

Science.gov (United States)

Fousekis, Konstantinos; Billis, Evdokia; Matzaroglou, Charalampos; Mylonas, Konstantinos; Koutsojannis, Constantinos; Tsepis, Elias

2017-05-01

Elastic bandages are commonly used in sports to treat and prevent sport injuries. To conduct a systematic review assessing the effectiveness of elastic bandaging in orthopedic- and sports-injury prevention and rehabilitation. The researchers searched the electronic databases MEDLINE, CINAHL, SPORTDiscus, EMBASE, and Physiotherapy Evidence Database (PEDro) with keywords elastic bandaging in combination, respectively, with first aid, sports injuries, orthopedic injuries, and sports injuries prevention and rehabilitation. Research studies were selected based on the use of the term elastic bandaging in the abstract. Final selection was made by applying inclusion and exclusion criteria to the full text. Studies were included if they were peer-reviewed clinical trials written in English on the effects of elastic bandaging for orthopedic-injury prevention and rehabilitation. Twelve studies met the criteria and were included in the final analysis. Data collected included number of participants, condition being treated, treatment used, control group, outcome measures, and results. Studies were critically analyzed using the PEDro scale. The studies in this review fell into 2 categories: studies in athletes (n = 2) and nonathletes (n = 10). All included trials had moderate to high quality, scoring ≥5 on the PEDro scale. The PEDro scores for the studies in athletes and nonathletes ranged from 5 to 6 out of 10 and from 5 to 8 out of 10, respectively. The quality of studies was mixed, ranging from higher- to moderate-quality methodological clinical trials. Overall, elastic bandaging can assist proprioceptive function of knee and ankle joint. Because of the moderate methodological quality and insufficient number of clinical trials, further effects of elastic bandaging could not be confirmed.

Lower Urinary Tract Injuries Following Blunt Trauma: A Review of Contemporary Management

Science.gov (United States)

Kong, Jennifer P. L; Bultitude, Matthew F; Royce, Peter; Gruen, Russell L; Cato, Alex; Corcoran, Niall M

2011-01-01

Lower urinary tract trauma, although relatively uncommon in blunt trauma, can lead to significant morbidity when diagnosed late or left untreated; urologists may only encounter a handful of these injuries in their career. This article reviews the literature and reports on the management of these injuries, highlighting the issues facing clinicians in this subspecialty. Also presented is a structured review detailing the mechanisms, classification, diagnosis, management, and complications of blunt trauma to the bladder and urethra. The prognosis for bladder rupture is excellent when treated. Significant intraperitoneal rupture or involvement of the bladder neck mandates surgical repair, whereas smaller extraperitoneal lacerations may be managed with catheterization alone. With the push for management of trauma patients in larger centers, urologists in these hospitals are seeing increasing numbers of lower urinary tract injuries. Prospective analysis may be achieved in these centers to address the current lack of Level 1 evidence. PMID:22114545

The impact of pediatric traumatic brain injury (TBI) on family functioning: a systematic review.

Science.gov (United States)

Rashid, Marghalara; Goez, Helly R; Mabood, Neelam; Damanhoury, Samah; Yager, Jerome Y; Joyce, Anthony S; Newton, Amanda S

2014-01-01

To explore the impact moderate to severe traumatic brain injury (TBI) in a child has on family functioning. The search was conducted using 9 bibliographic databases for articles published between 1980 and 2013. Two reviewers independently screened for inclusion and assessed study quality. Two reviewers extracted study data and a third checked for completeness and accuracy. Findings are presented by three domains: injury-related burden and stress, family adaptability, and family cohesion. Nine observational studies were included. Across the studies, differences between study groups for family functioning varied, but there was a trend for more dysfunction in families whose child had a severe TBI as compared to families whose child had a moderate TBI or orthopedic injury. In three studies, injury-associated burden was persistent post-injury and was highest in families whose child had a severe TBI followed by families with a child who had a moderate TBI. One study found fathers reported more family dysfunction caused by their child's injury compared to mothers. Two studies found that mothers' adaptability depended on social support and stress levels while fathers' adaptability was independent of these factors and injury severity. Moderate to severe TBI has a significant, long-standing impact on family functioning. Factors associated with family adaptability vary by parental role.

Mitochondrial Drugs for Alzheimer Disease

Directory of Open Access Journals (Sweden)

Xiongwei Zhu

2009-12-01

Full Text Available Therapeutic strategies for Alzheimer disease (AD have yet to offer a diseasemodifying effect to stop the debilitating progression of neurodegeneration and cognitive decline. Rather, treatments thus far are limited to agents that slow disease progression without halting it, and although much work towards a cure is underway, a greater understanding of disease etiology is certainly necessary for any such achievement. Mitochondria, as the centers of cellular metabolic activity and the primary generators of reactive oxidative species in the cell, received particular attention especially given that mitochondrial defects are known to contribute to cellular damage. Furthermore, as oxidative stress has come to the forefront of AD as a causal theory, and as mitochondrial damage is known to precede much of the hallmark pathologies of AD, it seems increasingly apparent that this metabolic organelle is ultimately responsible for much, if not all of disease pathogenesis. In this review, we review the role of neuronal mitochondria in the pathogenesis of AD and critically assess treatment strategies that utilize this upstream access point as a method for disease prevention. We suspect that, with a revived focus on mitochondrial repair and protection, an effective and realistic therapeutic agent can be successfully developed.

Exercise-Based Interventions for Injury Prevention in Tackle Collision Ball Sports: A Systematic Review.

Science.gov (United States)

Sewry, Nicola; Verhagen, Evert; Lambert, Mike; van Mechelen, Willem; Viljoen, Wayne; Readhead, Clint; Brown, James

2017-09-01

The injury burden in collision sports is relatively high compared to other team sports. Therefore, participants in these sports would benefit by having effective injury prevention programs. Exercise-based interventions have successfully reduced injuries in soccer, but evidence on exercise-based interventions in tackle collision sports is limited. The objective of this review is to systematically examine the evidence of exercise-based intervention programs reducing injuries in tackle collision sports. PubMed, EBSCOHost, and Web of Science were searched for articles published between January 1995 and December 2015. The methodological quality was assessed using an adapted Cochrane Bone Joint and Muscle Trauma Group quality assessment tool. The inclusion criteria were (1) (randomized) control trials and observational studies; (2) sporting codes: American, Australian and Gaelic Football, rugby union, and rugby league; (3) participants of any age or sex; (4) exercise-based, prehabilitative intervention; and (5) primary outcome was injury rate or incidence (injury risk). The exclusion criteria were (1) unavailability of full-text; and (2) article unavailable in English. Nine studies with a total of 3517 participants were included in this review. Seven of these studies showed a significant decrease in injury risk. These studies included three sporting codes and various age groups, making it difficult to make inferences. The two highest methodological quality studies found no effect of an exercise-based intervention on injury risk. There is evidence that exercise-based injury preventions can be beneficial in reducing injury risk in collision sports, but more studies of high methodological quality are required.

Injury and biomechanical perspectives on the rugby scrum:a review of the literature

OpenAIRE

Trewartha, Grant; Preatoni, Ezio; England, Michael E.; Stokes, Keith A.

2015-01-01

As a collision sport, rugby union has a relatively high overall injury incidence, with most injuries being associated with contact events. Historically, the set scrum has been a focus of the sports medicine community due to the perceived risk of catastrophic spinal injury during scrummaging. The contemporary rugby union scrum is a highly dynamic activity but to this point has not been well characterised mechanically. In this review, we synthesise the available research literature relating to ...

Mitochondrial Damage-Associated Molecular Patterns: From Inflammatory Signaling to Human Diseases

Directory of Open Access Journals (Sweden)

Serge Grazioli

2018-05-01

Full Text Available Over the recent years, much has been unraveled about the pro-inflammatory properties of various mitochondrial molecules once they are leaving the mitochondrial compartment. On entering the cytoplasm or the extracellular space, mitochondrial DAMPs (also known as mitochondrial alarmins can become pro-inflammatory and initiate innate and adaptive immune responses by activating cell surface and intracellular receptors. Current evidence indicates that uncontrolled and excessive release of mitochondrial DAMPs is associated with severity, has prognosis value in human diseases, and contributes to the dysregulated process observed in numerous inflammatory and autoimmune conditions, as well as in ischemic heart disease and cancer. Herein, we review that the expanding research field of mitochondrial DAMPs in innate immune responses and the current knowledge on the association between mitochondrial DAMPs and human diseases.

The mitochondrial toxicity of cysteine-S-conjugates: Studies with pentachlorobutadienyl-L-cysteine

International Nuclear Information System (INIS)

Wallin, A.

1990-01-01

Nephrotoxic cysteine conjugates, arising from mercapturate biosynthesis, can perturb the mitochondrial membrane potential and calcium homeostasis in renal epithelial cells. Activation of these cysteine conjugates to reactive species by mitochondrial β-lyases results in covalent binding and mitochondrial damage. PCBC and related cysteine conjugates inhibit ADP-stimulated respiration in mitochondria respiring on alpha-ketoglutrate/malate and succinate indicating that both dehydrogenases may be targets. The respiratory inhibition is blocked by aminooxyacetic acid, an inhibitor of the β-lyase. Hence, metabolic activation is required implying that covalent binding of reactive intermediates may be important to the mitochondrial injury. Binding of 35 S-fragments has been found for 5 conjugates with varying degrees of mitochondrial toxicity. PCBC is more lipophilic and has a higher affinity for cellular membranes than other cysteine conjugates. PCBC rapidly depolarizes the inner membrane potential resulting in an inhibition of mitochondrial oxidative phosphorylation and calcium upon sequestration. Consequently, mitochondria and renal epithelial cells exposed to PCBC show a sudden release of calcium upon exposure to PCBC which is followed by a later increase in state 4 respiration leading to an inhibition of oxidative phosphorylation. The primary effect of other cysteine conjugates is an inhibition of the dehydrogenases, thus inhibiting state 3 respiration

Polychlorinated Biphenyls Induce Mitochondrial Dysfunction in SH-SY5Y Neuroblastoma Cells.

Directory of Open Access Journals (Sweden)

Stefania Cocco

Full Text Available Chronic exposure to polychlorinated biphenyls (PCBs, ubiquitous environmental contaminants, can adversely affect the development and function of the nervous system. Here we evaluated the effect of PCB exposure on mitochondrial function using the PCB mixture Aroclor-1254 (A1254 in SH-SY5Y neuroblastoma cells. A 6-hour exposure to A1254 (5 μg/ml reduced cellular ATP production by 45%±7, and mitochondrial membrane potential, detected by TMRE, by 49%±7. Consistently, A1254 significantly decreased oxidative phosphorylation and aerobic glycolysis measured by extracellular flux analyzer. Furthermore, the activity of mitochondrial protein complexes I, II, and IV, but not V (ATPase, measured by BN-PAGE technique, was significantly reduced after 6-hour exposure to A1254. The addition of pyruvic acid during exposure to A1254 significantly prevent A1254-induced cell injury, restoring resting mitochondrial membrane potential, ATP levels, oxidative phosphorylation and aerobic glycolysis. Furthermore, pyruvic acid significantly preserved the activity of mitochondrial complexes I, II and IV and increased basal activity of complex V. Collectively, the present results indicate that the neurotoxicity of A1254 depends on the impairment of oxidative phosphorylation, aerobic glycolysis, and mitochondrial complexes I, II, and IV activity and it was counteracted by pyruvic acid.

Sleep disorders associated with primary mitochondrial diseases.

Science.gov (United States)

Ramezani, Ryan J; Stacpoole, Peter W

2014-11-15

Primary mitochondrial diseases are caused by heritable or spontaneous mutations in nuclear DNA or mitochondrial DNA. Such pathological mutations are relatively common in humans and may lead to neurological and neuromuscular complication that could compromise normal sleep behavior. To gain insight into the potential impact of primary mitochondrial disease and sleep pathology, we reviewed the relevant English language literature in which abnormal sleep was reported in association with a mitochondrial disease. We examined publication reported in Web of Science and PubMed from February 1976 through January 2014, and identified 54 patients with a proven or suspected primary mitochondrial disorder who were evaluated for sleep disturbances. Both nuclear DNA and mitochondrial DNA mutations were associated with abnormal sleep patterns. Most subjects who underwent polysomnography had central sleep apnea, and only 5 patients had obstructive sleep apnea. Twenty-four patients showed decreased ventilatory drive in response to hypoxia and/ or hyperapnea that was not considered due to weakness of the intrinsic muscles of respiration. Sleep pathology may be an underreported complication of primary mitochondrial diseases. The probable underlying mechanism is cellular energy failure causing both central neurological and peripheral neuromuscular degenerative changes that commonly present as central sleep apnea and poor ventilatory response to hyperapnea. Increased recognition of the genetics and clinical manifestations of mitochondrial diseases by sleep researchers and clinicians is important in the evaluation and treatment of all patients with sleep disturbances. Prospective population-based studies are required to determine the true prevalence of mitochondrial energy failure in subjects with sleep disorders, and conversely, of individuals with primary mitochondrial diseases and sleep pathology. © 2014 American Academy of Sleep Medicine.

Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries.

Science.gov (United States)

Rutkai, Ibolya; Dutta, Somhrita; Katakam, Prasad V; Busija, David W

2015-11-01

Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using N(ω)-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I-V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury. Copyright © 2015 the American Physiological Society.

Systematic review of military motor vehicle crash-related injuries.

Science.gov (United States)

Krahl, Pamela L; Jankosky, Christopher J; Thomas, Richard J; Hooper, Tomoko I

2010-01-01

Motor vehicle crashes account for nearly one third of U.S. military fatalities annually. The objective of this review is to summarize the published evidence on injuries due specifically to military motor vehicle (MMV) crashes. A search of 18 electronic databases identified English language publications addressing MMV crash-related injuries between 1970 and 2006 that were available to the general public. Documents limited in distribution to military or government personnel were not evaluated. Relevant articles were categorized by study design. The search identified only 13 studies related specifically to MMV crashes. Most were case reports or case series (n=8); only one could be classified as an intervention study. Nine of the studies were based solely on data from service-specific military safety centers. Few studies exist on injuries resulting from crashes of military motor vehicles. Epidemiologic studies that assess injury rates, type, severity, and risk factors are needed, followed by studies to evaluate targeted interventions and prevention strategies. Interventions currently underway should be evaluated for effectiveness, and those proven effective in the civilian community, such as graduated driver licensing, should be considered for implementation and evaluation in military populations. Published by Elsevier Inc.

Autistic disorder in 2 children with mitochondrial disorders.

Science.gov (United States)

Tsao, Chang-Yong; Mendell, Jerry R

2007-09-01

Autistic disorder is a heterogeneous disorder. The majority of the cases are idiopathic, and only a small number of the autistic children have associated secondary diagnosis. This article reports 2 children with mitochondrial disorders associated with autistic disorder fulfilling the diagnostic criteria of the American Psychiatric Association Manual of Psychiatric Diseases, 4th edition, and briefly reviews the literature on autistic disorder associated with mitochondrial disorders.

Mitochondrial Dysfunction in Lysosomal Storage Disorders

Directory of Open Access Journals (Sweden)

Mario de la Mata

2016-10-01

Full Text Available Lysosomal storage diseases (LSDs describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS, where neuronal dysfunction or loss results in progressive neurodegeneration and premature death. Many LSDs exhibit signs of mitochondrial dysfunction, which include mitochondrial morphological changes, decreased mitochondrial membrane potential (ΔΨm, diminished ATP production and increased generation of reactive oxygen species (ROS. Furthermore, reduced autophagic flux may lead to the persistence of dysfunctional mitochondria. Gaucher disease (GD, the LSD with the highest prevalence, is caused by mutations in the GBA1 gene that results in defective and insufficient activity of the enzyme β-glucocerebrosidase (GCase. Decreased catalytic activity and/or instability of GCase leads to accumulation of glucosylceramide (GlcCer and glucosylsphingosine (GlcSph in the lysosomes of macrophage cells and visceral organs. Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs.

Vildagliptin reduces cardiac ischemic-reperfusion injury in obese orchiectomized rats.

Science.gov (United States)

Pongkan, Wanpitak; Pintana, Hiranya; Jaiwongkam, Thidarat; Kredphoo, Sasiwan; Sivasinprasasn, Sivaporn; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2016-10-01

Obesity and testosterone deprivation are associated with coronary artery disease. Testosterone and vildagliptin (dipeptidyl peptidase-4 inhibitors) exert cardioprotection during ischemic-reperfusion (I/R) injury. However, the effect of these drugs on I/R heart in a testosterone-deprived, obese, insulin-resistant model is unclear. This study investigated the effects of testosterone and vildagliptin on cardiac function, arrhythmias and the infarct size in I/R heart of testosterone-deprived rats with obese insulin resistance. Orchiectomized (O) or sham operated (S) male Wistar rats were divided into 2 groups to receive normal diet (ND) or high-fat diet (HFD) for 12 weeks. Orchiectomized rats in each diet were divided to receive testosterone (2 mg/kg), vildagliptin (3 mg/kg) or the vehicle daily for 4 weeks. Then, I/R was performed by a 30-min left anterior descending coronary artery ligation, followed by a 120-min reperfusion. LV function, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. HFD groups developed insulin resistance at week 12. At week 16, cardiac function was impaired in NDO, HFO and HFS rats, but was restored in all testosterone- and vildagliptin-treated rats. During I/R injury, arrhythmia scores, infarct size and cardiac mitochondrial dysfunction were prominently increased in NDO, HFO and HFS rats, compared with those in NDS rats. Treatment with either testosterone or vildagliptin similarly attenuated these impairments during I/R injury. These finding suggest that both testosterone replacement and vildagliptin share similar efficacy for cardioprotection during I/R injury by decreasing the infarct size and attenuating cardiac mitochondrial dysfunction caused by I/R injury in testosterone-deprived rats with obese insulin resistance. © 2016 Society for Endocrinology.

Diagnostic Approach in Infants and Children with Mitochondrial Diseases

Directory of Open Access Journals (Sweden)

Ching-Shiang Chi

2015-02-01

The purpose of this study is to review the molecular classification scheme and associated phenotypes in infants and children with mitochondrial diseases, in addition to providing an overview of the basic biochemical reactions and genetic characteristics in the mitochondrion, clinical manifestations, and diagnostic methods. A diagnostic algorithm for identifying mitochondrial disorders in pediatric neurology patients is proposed.

Chaperone-protease networks in mitochondrial protein homeostasis.

Science.gov (United States)

Voos, Wolfgang

2013-02-01

As essential organelles, mitochondria are intimately integrated into the metabolism of a eukaryotic cell. The maintenance of the functional integrity of the mitochondrial proteome, also termed protein homeostasis, is facing many challenges both under normal and pathological conditions. First, since mitochondria are derived from bacterial ancestor cells, the proteins in this endosymbiotic organelle have a mixed origin. Only a few proteins are encoded on the mitochondrial genome, most genes for mitochondrial proteins reside in the nuclear genome of the host cell. This distribution requires a complex biogenesis of mitochondrial proteins, which are mostly synthesized in the cytosol and need to be imported into the organelle. Mitochondrial protein biogenesis usually therefore comprises complex folding and assembly processes to reach an enzymatically active state. In addition, specific protein quality control (PQC) processes avoid an accumulation of damaged or surplus polypeptides. Mitochondrial protein homeostasis is based on endogenous enzymatic components comprising a diverse set of chaperones and proteases that form an interconnected functional network. This review describes the different types of mitochondrial proteins with chaperone functions and covers the current knowledge of their roles in protein biogenesis, folding, proteolytic removal and prevention of aggregation, the principal reactions of protein homeostasis. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. Copyright © 2012 Elsevier B.V. All rights reserved.

Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction

Directory of Open Access Journals (Sweden)

Antonio eZorzano

2015-06-01

Full Text Available Mitochondrial dynamics is a term that encompasses the movement of mitochondria along the cytoskeleton, regulation of their architecture, and connectivity mediated by tethering and fusion/fission. The importance of these events in cell physiology and pathology has been partially unraveled with the identification of the genes responsible for the catalysis of mitochondrial fusion and fission. Mutations in two mitochondrial fusion genes (MFN2 and OPA1 cause neurodegenerative diseases, namely Charcot-Marie Tooth type 2A and autosomal dominant optic atrophy. Alterations in mitochondrial dynamics may be involved in the pathophysiology of prevalent neurodegenerative conditions. Moreover, impairment of the activity of mitochondrial fusion proteins dysregulates the function of hypothalamic neurons, leading to alterations in food intake and in energy homeostasis. Here we review selected findings in the field of mitochondrial dynamics and their relevance for neurodegeneration and hypothalamic dysfunction.

A systematic review of peer mentoring interventions for people with traumatic brain injury.

Science.gov (United States)

Morris, Richard Pg; Fletcher-Smith, Joanna C; Radford, Kathryn A

2017-08-01

This systematic review sought evidence concerning the effectiveness of peer mentoring for people with traumatic brain injury. Fourteen electronic databases were searched, including PsycINFO, MEDLINE, CINAHL, EMBASE and the Cochrane Library, from inception to September 21 2016. Ten grey literature databases, PROSPERO, two trials registers, reference lists and author citations were also searched. Studies which employed a model of one-to-one peer mentoring between traumatic brain injury survivors were included. Two reviewers independently screened all titles and abstracts before screening full texts of shortlisted studies. A third reviewer resolved disagreements. Two reviewers independently extracted data and assessed studies for quality and risk of bias. The search returned 753 records, including one identified through hand searching. 495 records remained after removal of duplicates and 459 were excluded after screening. Full texts were assessed for the remaining 36 studies and six met the inclusion criteria. All were conducted in the United States between 1996 and 2012 and employed a variety of designs including two randomised controlled trials. A total of 288 people with traumatic brain injury participated in the studies. No significant improvements in social activity level or social network size were found, but significant improvements were shown in areas including behavioural control, mood, coping and quality of life. There is limited evidence for the effectiveness of peer mentoring after traumatic brain injury. The available evidence comes from small-scale studies, of variable quality, without detailed information on the content of sessions or the 'active ingredient' of the interventions.

Epidemiology of Injuries in Women Playing Competitive Team Bat-or-Stick Sports: A Systematic Review and a Meta-Analysis.

Science.gov (United States)

Panagodage Perera, Nirmala Kanthi; Joseph, Corey; Kemp, Joanne Lyn; Finch, Caroline Frances

2018-03-01

Team bat-or-stick sports, including cricket, softball and hockey, are popular among women. However, little is known about the injury profile in this population. The aim was to describe the incidence, nature and anatomical location of injuries in bat-or-stick sports played by women in a competitive league. This review was prospectively registered (PROSPERO CRD42015026715). CINAHL, MEDLINE, PsycINFO, PubMed, SPORTDiscus were systematically searched from January 2000 to September 2016, inclusive. Peer-reviewed original research articles reporting the incidence, nature and anatomical location of injuries sustained by women aged 18 + years in competitive bat-or-stick sports were included. Two meta-analyses based on injury incidence proportions (injury IP) and injury rates per 1000 person-days of athletic exposure (AE) were performed. A total of 37 studies satisfied the inclusion criteria, and five had low risk of bias. The weighted injury IP was 0.42 [95% confidence interval (CI) 0.39-0.45]. The weighted injury rate was 6.12 (95% CI 6.05-6.18) overall, and greater in games [15.79 (95% CI 15.65-15.93)] than in practice [3.07 (95% CI 2.99-3.15)]. The ankle was the most commonly injured anatomical location, followed by the hand (including wrist and fingers), knee and head. Soft tissue and ligament injuries were most common types of injuries. Injury prevention in women's sports is a novel and emerging field of research interest. This review highlights that injury incidence is high among female bat-or-stick players, but little information is known about direct causal mechanisms. This review clearly establishes the need for enhancements to injury data collection. Without this information, it will not be possible to develop evidence-based injury prevention interventions.

Systematic review of self-reported prognosis in adults after mild traumatic brain injury

DEFF Research Database (Denmark)

Cassidy, John David; Cancelliere, Carol; Carroll, Linda J

2014-01-01

accepted and form our evidence base of prognostic studies. Of these, 23 addressed self-reported outcomes in adults, including 2 of the 3 original ICoMP research studies. These studies show that common postconcussion symptoms are not specific to MTBI/concussion and occur after other injuries as well. Poor...... recovery after MTBI is associated with poorer premorbid mental and physical health status and with more injury-related stress. Most recover over 1 year, but persistent symptoms are more likely in those with more acute symptoms and more emotional stress. CONCLUSIONS: Common subjective symptoms after MTBI......OBJECTIVE: To update the mild traumatic brain injury (MTBI) prognosis review published by the World Health Organization Task Force in 2004. DATA SOURCES: MEDLINE, PsycINFO, Embase, CINAHL, and SPORTDiscus were searched from 2001 to 2012. We included published, peer-reviewed studies with more than...

Interventions to prevent softball related injuries: a review of the literature

Science.gov (United States)

Pollack, K; Canham-Chervak, M; Gazal-Carvalho, C; Jones, B; Baker, S

2005-01-01

Objectives: To examine the published evidence on interventions to prevent softball related injuries among adults, and to encourage more epidemiologic research as a foundation for future softball injury prevention efforts. Methods: The authors reviewed literature identified from six electronic databases for studies on softball related injuries. The search was limited to studies written in the English language, published between 1970 and 2002, and involving adult populations. Research was excluded that evaluated baseball ("hard ball") related injuries or was aimed at injury treatment. Identified studies were categorized by study design. Intervention/prevention papers were evaluated further and described in detail. Results: The search strategy identified 39 studies specifically related to softball. Most studies were case reports/case series (n = 13) or descriptive studies (n = 11); only four were analytic or intervention/prevention studies. Studies collected data in a variety of ways, often without denominator data to permit calculation of injury rates. Studies also did not differentiate between slow or fast pitch softball activities and most did not mention the type of softball that was used. Conclusions: Surprisingly few studies exist on interventions to reduce injuries during softball, one of the most popular recreational sports in the US. Of the existing literature, much attention has been on sliding related injuries, which comprise only a segment of softball injuries. Basic epidemiologic studies describing the nature, severity, and risk factors for softball injuries in a variety of populations are needed, followed by additional intervention evaluation studies aimed at modifiable risk factors. PMID:16203835

Chemotherapeutic Drugs and Mitochondrial Dysfunction: Focus on Doxorubicin, Trastuzumab, and Sunitinib

Directory of Open Access Journals (Sweden)

Stefania Gorini

2018-01-01

Full Text Available Many cancer therapies produce toxic side effects whose molecular mechanisms await full elucidation. The most feared and studied side effect of chemotherapeutic drugs is cardiotoxicity. Also, skeletal muscle physiology impairment has been recorded after many chemotherapeutical treatments. However, only doxorubicin has been extensively studied for its side effects on skeletal muscle. Chemotherapeutic-induced adverse side effects are, in many cases, mediated by mitochondrial damage. In particular, trastuzumab and sunitinib toxicity is mainly associated with mitochondria impairment and is mostly reversible. Vice versa, doxorubicin-induced toxicity not only includes mitochondria damage but can also lead to a more robust and extensive cell injury which is often irreversible and lethal. Drugs interfering with mitochondrial functionality determine the depletion of ATP reservoirs and lead to subsequent reversible contractile dysfunction. Mitochondrial damage includes the impairment of the respiratory chain and the loss of mitochondrial membrane potential with subsequent disruption of cellular energetic. In a context of increased stress, AMPK has a key role in maintaining energy homeostasis, and inhibition of the AMPK pathway is one of the proposed mechanisms possibly mediating mitochondrial toxicity due to chemotherapeutics. Therapies targeting and protecting cell metabolism and energy management might be useful tools in protecting muscular tissues against the toxicity induced by chemotherapeutic drugs.

Mitochondrial dysfunction in the neuro-degenerative and cardio-degenerative disease, Friedreich's ataxia.

Science.gov (United States)

Chiang, Shannon; Kalinowski, Danuta S; Jansson, Patric J; Richardson, Des R; Huang, Michael L-H

2017-08-04

Mitochondrial homeostasis is essential for maintaining healthy cellular function and survival. The detrimental involvement of mitochondrial dysfunction in neuro-degenerative diseases has recently been highlighted in human conditions, such as Parkinson's, Alzheimer's and Huntington's disease. Friedreich's ataxia (FA) is another neuro-degenerative, but also cardio-degenerative condition, where mitochondrial dysfunction plays a crucial role in disease progression. Deficient expression of the mitochondrial protein, frataxin, is the primary cause of FA, which leads to adverse alterations in whole cell and mitochondrial iron metabolism. Dys-regulation of iron metabolism in these compartments, results in the accumulation of inorganic iron deposits in the mitochondrial matrix that is thought to potentiate oxidative damage observed in FA. Therefore, the maintenance of mitochondrial homeostasis is crucial in the progression of neuro-degenerative conditions, particularly in FA. In this review, vital mitochondrial homeostatic processes and their roles in FA pathogenesis will be discussed. These include mitochondrial iron processing, mitochondrial dynamics (fusion and fission processes), mitophagy, mitochondrial biogenesis, mitochondrial energy production and calcium metabolism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevention of anterior cruciate ligament injuries in sports. Part I: systematic review of risk factors in male athletes.

Science.gov (United States)

Alentorn-Geli, Eduard; Mendiguchía, Jurdan; Samuelsson, Kristian; Musahl, Volker; Karlsson, Jon; Cugat, Ramon; Myer, Gregory D

2014-01-01

The purpose of this study was to report a comprehensive literature review on the risk factors for anterior cruciate ligament (ACL) injuries in male athletes. All abstracts were read and articles of potential interest were reviewed in detail to determine on inclusion status for systematic review. Information regarding risk factors for ACL injuries in male athletes was extracted from all included studies in systematic fashion and classified as environmental, anatomical, hormonal, neuromuscular, or biomechanical. Data extraction involved general characteristics of the included studies (type of study, characteristics of the sample, type of sport), methodological aspects (for quality assessment), and the principal results for each type of risk factor. The principal findings of this systematic review related to the risk factors for ACL injury in male athletes are: (1) most of the evidence is related to environmental and anatomical risk factors; (2) dry weather conditions may increase the risk of non-contact ACL injuries in male athletes; (3) artificial turf may increase the risk of non-contact ACL injuries in male athletes; (4) higher posterior tibial slope of the lateral tibial plateau may increase the risk of non-contact ACL injuries in male athletes. Anterior cruciate ligament injury in male athletes likely has a multi-factorial aetiology. There is a lack of evidence regarding neuromuscular and biomechanical risk factors for ACL injury in male athletes. Future research in male populations is warranted to provide adequate prevention strategies aimed to decrease the risk of this serious injury in these populations.

Altering pyrroloquinoline quinone nutritional status modulates mitochondrial, lipid, and energy metabolism in rats.

Directory of Open Access Journals (Sweden)

Kathryn Bauerly

Full Text Available We have reported that pyrroloquinoline quinone (PQQ improves reproduction, neonatal development, and mitochondrial function in animals by mechanisms that involve mitochondrial related cell signaling pathways. To extend these observations, the influence of PQQ on energy and lipid relationships and apparent protection against ischemia reperfusion injury are described herein. Sprague-Dawley rats were fed a nutritionally complete diet with PQQ added at either 0 (PQQ- or 2 mg PQQ/Kg diet (PQQ+. Measurements included: 1 serum glucose and insulin, 2 total energy expenditure per metabolic body size (Wt(3/4, 3 respiratory quotients (in the fed and fasted states, 4 changes in plasma lipids, 5 the relative mitochondrial amount in liver and heart, and 6 indices related to cardiac ischemia. For the latter, rats (PQQ- or PQQ+ were subjected to left anterior descending occlusions followed by 2 h of reperfusion to determine PQQ's influence on infarct size and myocardial tissue levels of malondialdehyde, an indicator of lipid peroxidation. Although no striking differences in serum glucose, insulin, and free fatty acid levels were observed, energy expenditure was lower in PQQ- vs. PQQ+ rats and energy expenditure (fed state was correlated with the hepatic mitochondrial content. Elevations in plasma di- and triacylglyceride and β-hydroxybutryic acid concentrations were also observed in PQQ- rats vs. PQQ+ rats. Moreover, PQQ administration (i.p. at 4.5 mg/kg BW for 3 days resulted in a greater than 2-fold decrease in plasma triglycerides during a 6-hour fast than saline administration in a rat model of type 2 diabetes. Cardiac injury resulting from ischemia/reperfusion was more pronounced in PQQ- rats than in PQQ+ rats. Collectively, these data demonstrate that PQQ deficiency impacts a number of parameters related to normal mitochondrial function.

Elamipretide (SS-31 Ameliorates Isoflurane-Induced Long-Term Impairments of Mitochondrial Morphogenesis and Cognition in Developing Rats

Directory of Open Access Journals (Sweden)

Jian-Jun Yang

2017-04-01

Full Text Available Mitochondria are supposed to be involved in the early pathogenesis of general anesthesia (GA-induced neurotoxicity and long-term cognitive deficits in developing brains. However, effective pharmacologic agents targeted on mitochondria during GA exposure are lacking. This study explores the protective effects of mitochondrion-targeted antioxidant elamipretide (SS-31 on mitochondrial morphogenesis and cognition in developing rats exposed to isoflurane. Rat pups at postnatal day (PND 7 were exposed to 1.5% isoflurane for 6 h following intraperitoneal administration of elamipretide or vehicle with 30 min interval. The hippocampus was immediately removed for biochemical assays. Histopathological studies were conducted at PND 21, and behavioral tests were performed at PND 40 or 60. We found that early exposure to isoflurane caused remarkable reactive oxygen species (ROS accumulation, mitochondrial deformation and neuronal apoptosis in hippocampus. The injury occurrence ultimately gave rise to long-term cognitive deficits in developing rats. Interestingly, pretreatment with elamipretide not only provided protective effect against oxidative stress and mitochondrial damages, but also attenuated isoflurane-induced cognitive deficits. Our data support the notion that mitochondrial damage is an early and long lasting event of GA-induced injury and suggest that elamipretide might have clinically therapeutic benefits for pediatric patients undertaking GA.

Laryngeal Trauma Following an Inhalation Injury: A Review and Case Report.

Science.gov (United States)

Hogg, Gemma; Goswamy, Jay; Khwaja, Sadie; Khwaja, Nadeem

2017-05-01

The primary concern when managing a patient with inhalation injury is security of the airway. Airflow may be impeded by both edema of the upper airway and reduction of oxygen delivery to the lower respiratory tract. Although there has been much discussion regarding management of the latter, the focus of this article is the management of the former. This review aimed to determine the optimum management in burn victims with upper airway inhalation injury as an attempt to prevent laryngeal trauma leading to long-term voice disorders and upper airway dyspnea. We describe the case of a 57-year-old woman with significant inhalation injury and discuss the natural progression of her injuries and the laryngeal controversies surrounding her care. We conclude with advice on the optimal management of this condition based on our experience, combined with current best evidence. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

A systematic review of prognostic factors for return to work following work-related traumatic hand injury.

Science.gov (United States)

Shi, Qiyun; Sinden, Kathryn; MacDermid, Joy C; Walton, David; Grewal, Ruby

2014-01-01

Systematic review. Traumatic hand injuries are frequent cause of work related injuries and can result in prolonged durations of time loss from work. To systematically review available evidence to determine which prognostic factors predict return-to-work (RTW) following work-related traumatic hand injuries. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO from 1980 to September 2013 and reference lists of articles. Studies investigating any prognostic factors of RTW after traumatic hand injury were included. Two reviewers performed study selection, assessment of methodological quality and data extraction independently of each other. Identified factors were grouped into conceptual prognostic factor categories. We assessed 8 studies, which addressed 11 potential prognostic factors (i.e., sociodemographic factors, occupation, work compensation status, treatment related factors, impairment severity, location of injury, etc.). The quality of the studies was low to moderate. Across all included studies, RTW (original or modified work) occurred in over 60% of individuals by 6 months. There was consistent low-moderate quality evidence that individuals with more severe impairments and lower pre-injury income were less likely to RTW, and low-moderate quality evidence that age, gender and level of education had no impact on RTW. Evidence on other commonly cited prognostic factors were limited in the literature. Impairment severity and lower pre-injury income showed a consistent association with RTW following occupational hand injury, while other factors demonstrated no or variable effects across studies. Additional high-quality studies are warranted toward improving our understanding of the complex factors that mediate RTW following a traumatic work-related hand injury. 2a. Copyright © 2014 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage.

Science.gov (United States)

Kim, Seok-Jo; Cheresh, Paul; Jablonski, Renea P; Morales-Nebreda, Luisa; Cheng, Yuan; Hogan, Erin; Yeldandi, Anjana; Chi, Monica; Piseaux, Raul; Ridge, Karen; Michael Hart, C; Chandel, Navdeep; Scott Budinger, G R; Kamp, David W

2016-12-01

Alveolar epithelial cell (AEC) injury and mitochondrial dysfunction are important in the development of lung fibrosis. Our group has shown that in the asbestos exposed lung, the generation of mitochondrial reactive oxygen species (ROS) in AEC mediate mitochondrial DNA (mtDNA) damage and apoptosis which are necessary for lung fibrosis. These data suggest that mitochondrial-targeted antioxidants should ameliorate asbestos-induced lung. To determine whether transgenic mice that express mitochondrial-targeted catalase (MCAT) have reduced lung fibrosis following exposure to asbestos or bleomycin and, if so, whether this occurs in association with reduced AEC mtDNA damage and apoptosis. Crocidolite asbestos (100µg/50µL), TiO 2 (negative control), bleomycin (0.025 units/50µL), or PBS was instilled intratracheally in 8-10 week-old wild-type (WT - C57Bl/6J) or MCAT mice. The lungs were harvested at 21d. Lung fibrosis was quantified by collagen levels (Sircol) and lung fibrosis scores. AEC apoptosis was assessed by cleaved caspase-3 (CC-3)/Surfactant protein C (SFTPC) immunohistochemistry (IHC) and semi-quantitative analysis. AEC (primary AT2 cells from WT and MCAT mice and MLE-12 cells) mtDNA damage was assessed by a quantitative PCR-based assay, apoptosis was assessed by DNA fragmentation, and ROS production was assessed by a Mito-Sox assay. Compared to WT, crocidolite-exposed MCAT mice exhibit reduced pulmonary fibrosis as measured by lung collagen levels and lung fibrosis score. The protective effects in MCAT mice were accompanied by reduced AEC mtDNA damage and apoptosis. Similar findings were noted following bleomycin exposure. Euk-134, a mitochondrial SOD/catalase mimetic, attenuated MLE-12 cell DNA damage and apoptosis. Finally, compared to WT, asbestos-induced MCAT AT2 cell ROS production was reduced. Our finding that MCAT mice have reduced pulmonary fibrosis, AEC mtDNA damage and apoptosis following exposure to asbestos or bleomycin suggests an important role

A Systematic Review of Non-Invasive Pharmacologic Neuroprotective Treatments for Acute Spinal Cord Injury

Science.gov (United States)

Okon, Elena; Hillyer, Jessica; Mann, Cody; Baptiste, Darryl; Weaver, Lynne C.; Fehlings, Michael G.; Tetzlaff, Wolfram

2011-01-01

Abstract An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically review the available pre-clinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we review treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications, or are available in a form that could be administered to humans. These include: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in-vivo animal model was utilized to assess the efficacy of the therapy in a traumatic SCI paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the pre-clinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation. PMID:20146558

What types of unintentional injuries kill our children? Do infants die of the same types of injuries? A systematic review

Directory of Open Access Journals (Sweden)

Janete Honda Imamura

Full Text Available The objective of this study was to review mortality from external causes (accidental injury in children and adolescents in systematically selected journals. This was a systematic review of the literature on mortality from accidental injury in children and adolescents. We searched the Pubrvled, Latin-American and Caribbean Health Sciences and Excerpta Medica databases for articles published between July of 2001 and June of 2011. National data from official agencies, retrieved by manual searches, were also reviewed. We reviewed 15 journal articles, the 2011 edition of a National Safety Council publication and 2010 statistical data from the Brazilian National Ministry of Health Mortality Database. Most published data were related to high-income countries. Mortality from accidental injury was highest among children less than 1 year of age. Accidental threats to breathing (non-drowning threats constituted the leading cause of death among this age group in the published articles. Across the pediatric age group in the surveyed studies, traffic accidents were the leading cause of death, followed by accidental drowning and submersion. Traffic accidents constitute the leading external cause of accidental death among children in the countries understudy. However, infants were vulnerable to external causes, particularly to accidental non-drowning threats to breathing, and this age group had the highest mortality rates for external causes. Actions to reduce such events are suggested. Further studies investigating the occurrence of accidental deaths in low-income countries are needed to improve the understanding of these preventable events.

Autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury induced by albumin overload.

Science.gov (United States)

Tan, Jin; Wang, Miaohong; Song, Shuling; Miao, Yuyang; Zhang, Qiang

2018-01-10

Proteinuria (albuminuria) is an important cause of aggravating tubulointerstitial injury. Previous studies have shown that autophagy activation can alleviate renal tubular epithelial cell injury caused by urinary protein, but the mechanism is not clear. Here, we investigated the role of clearance of damaged mitochondria in this protective effect. We found that albumin overload induces a significant increase in turnover of LC3-II and decrease in p62 protein level in renal proximal tubular (HK-2) cells in vitro. Albumin overload also induces an increase in mitochondrial damage. ALC, a mitochondrial torpent, alleviates mitochondrial damage induced by albumin overload and also decreases autophagy, while mitochondrial damage revulsant CCCP further increases autophagy. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the amount of damaged mitochondria and the level of apoptosis induced by albumin overload. In contrast, blocking autophagy with chloroquine exerted an opposite effect. Taken together, our results indicated autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury caused by albumin overload. This further confirms previous research that autophagy activation is an adaptive response in renal tubular epithelial cells after urinary protein overload.

Medical-attention injuries in community Australian football: a review of 30 years of surveillance data from treatment sources.

Science.gov (United States)

Ekegren, Christina L; Gabbe, Belinda J; Finch, Caroline F

2015-03-01

In recent reports, Australian football has outranked other team sports in the frequency of hospitalizations and emergency department (ED) presentations. Understanding the profile of these and other "medical-attention" injuries is vital for developing preventive strategies that can reduce health costs. The objective of this review was to describe the frequency and profile of Australian football injuries presenting for medical attention. A systematic search was carried out to identify peer-reviewed articles and reports presenting original data about Australian football injuries from treatment sources (hospitals, EDs, and health-care clinics). Data extracted included injury frequency and rate, body region, and nature and mechanism of injury. Following literature search and review, 12 publications were included. In most studies, Australian football contributed the greatest number of injuries out of any sport or recreation activity. Hospitals and EDs reported a higher proportion of upper limb than lower limb injuries, whereas the opposite was true for sports medicine clinics. In hospitals, fractures and dislocations were most prevalent out of all injuries. In EDs and clinics, sprains/strains were most common in adults and superficial injuries were predominant in children. Most injuries resulted from contact with other players or falling. The upper limb was the most commonly injured body region for Australian football presentations to hospitals and EDs. Strategies to prevent upper limb injuries could reduce associated public health costs. However, to understand the full extent of the injury problem in football, treatment source surveillance systems should be supplemented with other datasets, including community club-based collections.

Neuromuscular Control Deficits and the Risk of Subsequent Injury after a Concussion: A Scoping Review.

Science.gov (United States)

Howell, David R; Lynall, Robert C; Buckley, Thomas A; Herman, Daniel C

2018-05-01

An emerging area of research has identified that an increased risk of musculoskeletal injury may exist upon returning to sports after a sport-related concussion. The mechanisms underlying this recently discovered phenomenon, however, remain unknown. One theorized reason for this increased injury risk includes residual neuromuscular control deficits that remain impaired despite clinical recovery. Thus, the objectives of this review were: (1) to summarize the literature examining the relationship between concussion and risk of subsequent injury and (2) to summarize the literature for one mechanism with a theorized association with this increased injury risk, i.e., neuromuscular control deficits observed during gait after concussion under dual-task conditions. Two separate reviews were conducted consistent with both specified objectives. Studies published before 9 December, 2016 were identified using PubMed, Web of Science, and Academic Search Premier (EBSCOhost). Inclusion for the objective 1 search included dependent variables of quantitative measurements of musculoskeletal injury after concussion. Inclusion criteria for the objective 2 search included dependent variables pertaining to gait, dynamic balance control, and dual-task function. A total of 32 studies were included in the two reviews (objective 1 n = 10, objective 2 n = 22). According to a variety of study designs, athletes appear to have an increased risk of sustaining a musculoskeletal injury following a concussion. Furthermore, dual-task neuromuscular control deficits may continue to exist after patients report resolution of concussion symptoms, or perform normally on other clinical concussion tests. Therefore, musculoskeletal injury risk appears to increase following a concussion and persistent motor system and attentional deficits also seem to exist after a concussion. While not yet experimentally tested, these motor system and attentional deficits may contribute to the risk of sustaining a

Lebetin 2, a Snake Venom-Derived Natriuretic Peptide, Attenuates Acute Myocardial Ischemic Injury through the Modulation of Mitochondrial Permeability Transition Pore at the Time of Reperfusion.

Directory of Open Access Journals (Sweden)

Bochra Tourki

Full Text Available Cardiac ischemia is one of the leading causes of death worldwide. It is now well established that natriuretic peptides can attenuate the development of irreversible ischemic injury during myocardial infarction. Lebetin 2 (L2 is a new discovered peptide isolated from Macrovipera lebetina venom with structural similarity to B-type natriuretic peptide (BNP. Our objectives were to define the acute cardioprotective actions of L2 in isolated Langendorff-perfused rat hearts after regional or global ischemia-reperfusion (IR. We studied infarct size, left ventricular contractile recovery, survival protein kinases and mitochondrial permeability transition pore (mPTP opening in injured myocardium. L2 dosage was determined by preliminary experiments at its ability to induce cyclic guanosine monophosphate (cGMP release without changing hemodynamic effects in normoxic hearts. L2 was found to be as effective as BNP in reducing infarct size after the induction of either regional or global IR. Both peptides equally improved contractile recovery after regional IR, but only L2 increased coronary flow and reduced severe contractile dysfunction after global ischemia. Cardioprotection afforded by L2 was abolished after isatin or 5-hydroxydecanote pretreatment suggesting the involvement of natriuretic peptide receptors and mitochondrial KATP (mitoKATP channels in the L2-induced effects. L2 also increased survival protein expression in the reperfused myocardium as evidenced by phosphorylation of signaling pathways PKCε/ERK/GSK3β and PI3K/Akt/eNOS. IR induced mitochondrial pore opening, but this effect was markedly prevented by L2 treatment. These data show that L2 has strong cardioprotective effect in acute ischemia through stimulation of natriuretic peptide receptors. These beneficial effects are mediated, at least in part, by mitoKATP channel opening and downstream activated survival kinases, thus delaying mPTP opening and improving IR-induced mitochondrial

Experiences of giving and receiving care in traumatic brain injury: An integrative review.

Science.gov (United States)

Kivunja, Stephen; River, Jo; Gullick, Janice

2018-04-01

To synthesise the literature on the experiences of giving or receiving care for traumatic brain injury for people with traumatic brain injury, their family members and nurses in hospital and rehabilitation settings. Traumatic brain injury represents a major source of physical, social and economic burden. In the hospital setting, people with traumatic brain injury feel excluded from decision-making processes and perceive impatient care. Families describe inadequate information and support for psychological distress. Nurses find the care of people with traumatic brain injury challenging particularly when experiencing heavy workloads. To date, a contemporary synthesis of the literature on people with traumatic brain injury, family and nurse experiences of traumatic brain injury care has not been conducted. Integrative literature review. A systematic search strategy guided by the PRISMA statement was conducted in CINAHL, PubMed, Proquest, EMBASE and Google Scholar. Whittemore and Knafl's (Journal of Advanced Nursing, 52, 2005, 546) integrative review framework guided data reduction, data display, data comparison and conclusion verification. Across the three participant categories (people with traumatic brain injury/family members/nurses) and sixteen subcategories, six cross-cutting themes emerged: seeking personhood, navigating challenging behaviour, valuing skills and competence, struggling with changed family responsibilities, maintaining productive partnerships and reflecting on workplace culture. Traumatic brain injury creates changes in physical, cognitive and emotional function that challenge known ways of being in the world for people. This alters relationship dynamics within families and requires a specific skill set among nurses. Recommendations include the following: (i) formal inclusion of people with traumatic brain injury and families in care planning, (ii) routine risk screening for falls and challenging behaviour to ensure that controls are based on

Selective replacement of mitochondrial DNA increases the cardioprotective effect of chronic continuous hypoxia in spontaneously hypertensive rats

Czech Academy of Sciences Publication Activity Database

Neckář, Jan; Svatoňová, Anna; Weissová, Romana; Drahota, Zdeněk; Zajíčková, Pavlína; Brabcová, I.; Kolář, D.; Alánová, Petra; Vašinová, Jana; Šilhavý, Jan; Hlaváčková, Markéta; Tauchmannová, Kateřina; Milerová, Marie; Ošťádal, Bohuslav; Červenka, L.; Žurmanová, J.; Kalous, M.; Nováková, Olga; Novotný, J.; Pravenec, Michal; Kolář, František

2017-01-01

Roč. 131, č. 9 (2017), s. 865-881 ISSN 0143-5221 R&D Projects: GA ČR(CZ) GA13-10267S; GA ČR(CZ) GB14-36804G; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 Keywords : chronic hypoxia * heart * hypertension * ischaemia–reperfusion injury * mitochondrial genome * mitochondrial permeability transition pore Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Physiology (including cytology) Impact factor: 4.936, year: 2016

Mitochondrial metabolism and the control of vascular smooth muscle cell proliferation

Directory of Open Access Journals (Sweden)

Mario eChiong

2014-12-01

Full Text Available Differentiation and dedifferentiation of vascular smooth muscle cells (VSMCs are essential processes of vascular development. VSMCs have biosynthetic, proliferative and contractile roles in the vessel wall. Alterations in the differentiated state of the VSMCs play a critical role in the pathogenesis of a variety of cardiovascular diseases, including atherosclerosis, hypertension and vascular stenosis. This review provides an overview of the current state of knowledge of molecular mechanisms involved in the control of VSMC proliferation, with particular focus on mitochondrial metabolism. Mitochondrial activity can be controlled by regulating mitochondrial dynamics, i.e. mitochondrial fusion and fission, and by regulating mitochondrial calcium handling through the interaction with the endoplasmic reticulum (ER. Alterations in both VSMC proliferation and mitochondrial function can be triggered by dysregulation of mitofusin-2, a small GTPase associated with mitochondrial fusion and mitochondrial-ER interaction. Several lines of evidence highlight the relevance of mitochondrial metabolism in the control of VSMC proliferation, indicating a new area to be explored in the treatment of vascular diseases.

The impact of pre-injury anticoagulation therapy in the older adult patient experiencing a traumatic brain injury: A systematic review.

Science.gov (United States)

Smith, Karen; Weeks, Susan

2012-01-01

The objective of this systematic review is to synthesize the best available evidence on the impact of pre-injury anticoagulation therapy in the older adult patient who experiences a traumatic brain injury. Trauma in the elderly remains one of the most challenging problems for healthcare providers in the 21 century. The most recent United States (U.S.) census estimates that by the year 2020 more than 52 million Americans will be age 65 years or older, and one million of those will live to be over 100 years of age. In the older adult population, classified as age 65 years or greater, the two leading causes of injury were reported as motor vehicle crashes (MVC) and falls. We have become increasingly aware of the unique physiologic changes in this population that make them more susceptible to succumb to traumatic injuries than their younger counterparts. This is especially true in the anticoagulated patient with a traumatic brain injury.Traumatic brain injury (TBI) is defined as an injury occurring when an external force traumatizes the brain. It may also be known as an intracranial or head injury. TBI is classified depending on the mechanism of injury (blunt or penetrating), severity, and location of the assault. Damage to the brain, skull, and/or scalp transpires. TBI is the leading cause of death and disability in the U.S, and persons of all ages, races, ethnicities, and incomes are affected. In the past five to ten years, trauma services have recorded an increase in major trauma admissions of patients age 65 years and older. In review of the literature to date, it is recognized that outcomes following moderate to severe TBI in older adults are poor, with high rates of significant disability and mortality reported. A recent Australian study reported that 28% of older adults died in the hospital following a TBI and in Finland adults aged 75 years and older had the highest rates of TBI related hospitalizations and death. According to a systematic review of European

Social and ethical issues in mitochondrial donation.

Science.gov (United States)

Dimond, Rebecca

2015-09-01

The UK is at the forefront of mitochondrial science and is currently the only country in the world to legalize germ-line technologies involving mitochondrial donation. However, concerns have been raised about genetic modification and the 'slippery slope' to designer babies. This review uses academic articles, newspaper reports and public documents. Mitochondrial donation offers women with mitochondrial disease an opportunity to have healthy, genetically related children. Key areas of disagreement include safety, the creation of three-parent babies, impact on identity, implications for society, definitions of genetic modification and reproductive choice. The UK government legalized the techniques in March 2015. Scientific and medical communities across the world followed the developments with interest. It is expected that the first cohort of 'three parent' babies will be born in the UK in 2016. Their health and progress will be closely monitored. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Neuropathic pain prevalence following spinal cord injury: A systematic review and meta-analysis.

Science.gov (United States)

Burke, D; Fullen, B M; Stokes, D; Lennon, O

2017-01-01

Following spinal cord injury (SCI), chronic pain is a common secondary complication with neuropathic pain (NP) cited as one of the most distressing and debilitating conditions leading to poor quality of life, depression and sleep disturbances. Neuropathic pain presenting at or below the level of injury is largely refractory to current pharmacological and physical treatments. No consensus on the prevalence of NP post SCI currently exists, hence this systematic review was undertaken. The review comprised three phases: a methodological assessment of databases [PubMed, Embase, Web of Knowledge, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library and Physiotherapy Evidence Database (PEDro)] identifying potential papers and screening for inclusion criteria by two independent reviewers; data extraction; and finally rating of internal validity and strength of the evidence, using a published valid and reliable scale. Meta-analysis estimated pooled point prevalence rates using a random effects model. In total, 17 studies involving 2529 patients were included in the review. Overall point prevalence rates for NP were established at 53% (38.58-67.47); 19% (13.26-26.39) for at-level NP and 27% (19.89-34.61) for below-level NP, with high heterogeneity noted (I 2  = 84-93%). Prevalence rates for NP following SCI are high. Future studies should include established definitions, classification systems and assessment tools for NP at defined time points post SCI to follow the trajectory of this problem across the lifespan and include indices of sleep, mood and interference to allow for appropriate, optimal and timely NP management for each patient. WHAT DOES THIS REVIEW ADD?: This is the first systematic review and meta-analysis to record pooled point prevalence of neuropathic pain post spinal cord injury at 53%. Additional pooled analysis shows that neuropathic pain is more common below the level of lesion, in patients with tetraplegia, older patients

Identification of the effects of peripheral nerves injury on the muscle control - A review

Science.gov (United States)

Cabaj, Anna; Zmyslowski, Wojciech

2011-01-01

Impairment of motor function following peripheral nerve injury is a serious clinical problem. Generally nerve injury leads to erroneous control of muscle activity that results in gait and voluntary movement abnormalities followed by muscle atrophy. This article presents a review of studies on the effects of peripheral nerve injury on the motor system performed on animal models. We focused our attention on the results that are fundamental for better understanding of the degenerative and regenerative processes induced by nerve injury as well as of the mechanisms of structural changes in neuronal networks controlling movement. Quoted results are also important for clinical applications because they allow to develop new diagnostic and therapeutic techniques that can be used after nerve injury inducing motor deficits. However, till now no efficient therapy inducing satisfactory recovery was found. There is still a need to continue an advanced basic research directed to develop effective therapies. Thus the aim of this review is to compare the results of recent studies performed on various animal models in order to propose new methods for identification of mechanisms responsible for muscle deficits and propose targets for new pharmacological therapies.

A Review of Dysphagia Presentation and Intervention Following Traumatic Spinal Injury: An Understudied Population.

Science.gov (United States)

Valenzano, Teresa J; Waito, Ashley A; Steele, Catriona M

2016-10-01

Dysphagia is reported to be a common secondary complication for individuals with traumatic spinal injuries. Different etiologies of traumatic spinal injuries may lead to different profiles of swallowing impairment. We conducted a systematic review to determine the characteristics of dysphagia after traumatic spinal injury and to describe interventions currently used to improve swallowing function in this population. A comprehensive multiengine literature search identified 137 articles of which five were judged to be relevant. These underwent review for study quality, rating for level of evidence, and data extraction. The literature describing dysphagia after traumatic spinal injury was comprised predominantly of low-level evidence and single case reports. Aspiration, pharyngeal residue, and decreased/absent hyolaryngeal elevation were found to be common characteristics of dysphagia in this population. The most commonly used swallowing interventions included tube feeding, compensatory swallowing strategies, and steroids/antibiotics. Improvement in swallowing function following swallowing intervention was reported in all studies; however, there was no control for spontaneous recovery. The results demonstrate a need for high-quality research to profile the pathophysiology of dysphagia after traumatic spinal injury and controlled studies to demonstrate the efficacy of swallowing interventions in this population.

Mitochondrial oxidative function and type 2 diabetes

DEFF Research Database (Denmark)

Rabøl, Rasmus; Boushel, Robert; Dela, Flemming

2006-01-01

The cause of insulin resistance and type 2 diabetes is unknown. The major part of insulin-mediated glucose disposal takes place in the skeletal muscle, and increased amounts of intramyocellular lipid has been associated with insulin resistance and linked to decreased activity of mitochondrial...... oxidative phosphorylation. This review will cover the present knowledge and literature on the topics of the activity of oxidative enzymes and the electron transport chain (ETC) in skeletal muscle of patients with type 2 diabetes. Different methods of studying mitochondrial function are described, including...... biochemical measurements of oxidative enzyme and electron transport activity, isolation of mitochondria for measurements of respiration, and ATP production and indirect measurements of ATP production using nuclear magnetic resonance (NMR) - spectroscopy. Biochemical markers of mitochondrial content are also...

Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.

Science.gov (United States)

He, J; Cooper, H M; Reyes, A; Di Re, M; Sembongi, H; Litwin, T R; Gao, J; Neuman, K C; Fearnley, I M; Spinazzola, A; Walker, J E; Holt, I J

2012-07-01

Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.

Clinical evidence of inflammation driving secondary brain injury: A systematic review

Science.gov (United States)

Hinson, Holly E.; Rowell, Susan; Schreiber, Martin

2015-01-01

Background Despite advances in both prevention and treatment, traumatic brain injury (TBI) remains one of the most burdensome diseases; 2% of the US population currently lives with disabilities resulting from TBI. Recent advances in the understanding of inflammation and its impact on the pathophysiology of trauma have increased the interest in inflammation as a possible mediator in TBI outcome. Objectives The goal of this systematic review is to address the question: “What is the evidence in humans that inflammation is linked to secondary brain injury?” As the experimental evidence has been well described elsewhere, this review will focus on the clinical evidence for inflammation as a mechanism of secondary brain injury. Data Sources Medline database (1996-Week 1 June 2014), Pubmed and Google Scholar databases were queried for relevant studies. Study Eligibility Criteria Studies were eligible if participants were adults and/or children who sustained moderate or severe TBI in the acute phase of injury, published in English. Studies published in the last decade (since 2004) were preferentially included. Trials could be observational or interventional in nature. Appraisal and Synthesis Methods To address the quality of the studies retrieved, we applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria to assess the limitations of the included studies. Results Trauma initiates local central nervous system as well as systemic immune activation. Numerous observational studies describe elevation of pro-inflammatory cytokines that are associated with important clinical variables including neurologic outcome and mortality. A small number of clinical trials have included immunomodulating strategies, but no intervention to date has proven effective in improving outcomes after TBI. Limitations Inclusion of studies not initially retrieved by the search terms may have biased our results. Additionally, some reports may have been

Prospects for therapeutic mitochondrial transplantation.

Science.gov (United States)

Gollihue, Jenna L; Rabchevsky, Alexander G

2017-07-01

Mitochondrial dysfunction has been implicated in a multitude of diseases and pathological conditions- the organelles that are essential for life can also be major players in contributing to cell death and disease. Because mitochondria are so well established in our existence, being present in all cell types except for red blood cells and having the responsibility of providing most of our energy needs for survival, then dysfunctional mitochondria can elicit devastating cellular pathologies that can be widespread across the entire organism. As such, the field of "mitochondrial medicine" is emerging in which disease states are being targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. New and compelling research investigating novel techniques for mitochondrial transplantation to replace damaged or dysfunctional mitochondria with exogenous healthy mitochondria has shown promising results, including tissue sparing accompanied by increased energy production and decreased oxidative damage. Various experimental techniques have been attempted and each has been challenged to accomplish successful transplantation. The purpose of this review is to present the history of mitochondrial transplantation, the different techniques used for both in vitro and in vivo delivery, along with caveats and pitfalls that have been discovered along the way. Results from such pioneering studies are promising and could be the next big wave of "mitochondrial medicine" once technical hurdles are overcome. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Dog bite injuries in children – a review of data from a South African ...

African Journals Online (AJOL)

Background and objective. Dog bites are a major cause of preventable traumatic injury in the paediatric population. We aimed to determine the epidemiology of dog bite injuries in a group of South African children with a view to developing potential preventive strategies. Design, setting, subjects. A retrospective review was ...

Three-dimensional analysis of somatic mitochondrial dynamics in fission-deficient injured motor neurons using FIB/SEM.

Science.gov (United States)

Tamada, Hiromi; Kiryu-Seo, Sumiko; Hosokawa, Hiroki; Ohta, Keisuke; Ishihara, Naotada; Nomura, Masatoshi; Mihara, Katsuyoshi; Nakamura, Kei-Ichiro; Kiyama, Hiroshi

2017-08-01

Mitochondria undergo morphological changes through fusion and fission for their quality control, which are vital for neuronal function. In this study, we examined three-dimensional morphologies of mitochondria in motor neurons under normal, nerve injured, and nerve injured plus fission-impaired conditions using the focused ion beam/scanning electron microscopy (FIB/SEM), because the FIB/SEM technology is a powerful tool to demonstrate both 3D images of whole organelle and the intra-organellar structure simultaneously. Crossing of dynamin-related protein 1 (Drp1) gene-floxed mice with neuronal injury-specific Cre driver mice, Atf3:BAC Tg mice, allowed for Drp1 ablation specifically in injured neurons. FIB/SEM analysis demonstrated that somatic mitochondrial morphologies in motor neurons were not altered before or after nerve injury. However, the fission impairment resulted in prominent somatic mitochondrial enlargement, which initially induced complex morphologies with round regions and long tubular processes, subsequently causing a decrease in the number of processes and further enlargement of the round regions, which eventually resulted in big spheroidal mitochondria without processes. The abnormal mitochondria exhibited several degradative morphologies: local or total cristae collapse, vacuolization, and mitophagy. These suggest that mitochondrial fission is crucial for maintaining mitochondrial integrity in injured motor neurons, and multiple forms of mitochondria degradation may accelerate neuronal degradation. © 2017 Wiley Periodicals, Inc.

How Do People Stop Non-Suicidal Self-Injury? A Systematic Review.

Science.gov (United States)

Mummé, Tess Alexandra; Mildred, Helen; Knight, Tess

2017-07-03

The current paper reviews extant quantitative and qualitative literature into how Non-Suicidal Self-Injury cessation occurs, and individuals' experiences of stopping. Specific search criteria utilizing a PRISMA format were used across 5 databases, which resulted in 454 papers being identified. After utilizing exclusion criteria and then review, nine of the 454 papers identified were retained for extensive synthesis and critique. Results from 8 of the identified papers indicated that both intra and inter personal factors can influence self-injury cessation. These include: family support, self-esteem, emotional regulation, and professional help. Only 1 paper articulated a cessation process, describing it as a procedural event of developing interpersonal strength, then implementing alternative coping strategies. Limitations and implications of the studies are reported, concluding that further research is warranted to inform effective prevention and treatment strategies to ameliorate this growing public health concern.

Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells

OpenAIRE

Kim, Ji-Seok; Kim, Boa; Lee, Hojun; Thakkar, Sunny; Babbitt, Dianne M.; Eguchi, Satoru; Brown, Michael D.; Park, Joon-Young

2015-01-01

This study assesses effects of aerobic exercise training on the release of microparticles from endothelial cells and corroborates these findings using an in vitro experimental exercise stimulant, laminar shear stress. Furthermore, this study demonstrated that shear stress-induced mitochondrial biogenesis mediates these effects against endothelial cell activation and injury.

Mitochondrial miRNA (MitomiR): a new player in cardiovascular health.

Science.gov (United States)

Srinivasan, Hemalatha; Das, Samarjit

2015-10-01

Cardiovascular disease is one of the major causes of human morbidity and mortality in the world. MicroRNAs (miRNAs) are small RNAs that regulate gene expression and are known to be involved in the pathogenesis of heart diseases, but the translocation phenomenon and the mode of action in mitochondria are largely unknown. Recent mitochondrial proteome analysis unveiled at least 2000 proteins, of which only 13 are made by the mitochondrial genome. There are numerous studies demonstrating the translocation of proteins into the mitochondria and also translocation of ribosomal RNA (viz., 5S rRNA) into mitochondria. Recent studies have suggested that miRNAs contain sequence elements that affect their subcellular localization, particularly nuclear localization. If there are sequence elements that direct miRNAs to the nucleus, it is also possible that similar sequence elements exist to direct miRNAs to the mitochondria. In this review we have summarized most of the miRNAs that have been shown to play an important role in mitochondrial function, either by regulating mitochondrial genes or by regulating nuclear genes that are known to influence mitochondrial function. While the focus of this review is cardiovascular diseases, we also illustrate the role of mitochondrial miRNA (MitomiR) in the initiation and progression of various diseases, including cardiovascular diseases, metabolic diseases, and cancer. Our goal here is to summarize the miRNAs that are localized to the mitochondrial fraction of cells, and how these miRNAs modulate cardiovascular health.

Mitochondrial protein adducts formation and mitochondrial dysfunction during N-acetyl-m-aminophenol (AMAP)-induced hepatotoxicity in primary human hepatocytes

International Nuclear Information System (INIS)

Xie, Yuchao; McGill, Mitchell R.; Du, Kuo; Dorko, Kenneth; Kumer, Sean C.; Schmitt, Timothy M.; Ding, Wen-Xing; Jaeschke, Hartmut

2015-01-01

3′-Hydroxyacetanilide or N-acetyl-meta-aminophenol (AMAP) is generally regarded as a non-hepatotoxic analog of acetaminophen (APAP). Previous studies demonstrated the absence of toxicity after AMAP in mice, hamsters, primary mouse hepatocytes and several cell lines. In contrast, experiments with liver slices suggested that it may be toxic to human hepatocytes; however, the mechanism of toxicity is unclear. To explore this, we treated primary human hepatocytes (PHH) with AMAP or APAP for up to 48 h and measured several parameters to assess metabolism and injury. Although less toxic than APAP, AMAP dose-dependently triggered cell death in PHH as indicated by alanine aminotransferase (ALT) release and propidium iodide (PI) staining. Similar to APAP, AMAP also significantly depleted glutathione (GSH) in PHH and caused mitochondrial damage as indicated by glutamate dehydrogenase (GDH) release and the JC-1 assay. However, unlike APAP, AMAP treatment did not cause relevant c-jun-N-terminal kinase (JNK) activation in the cytosol or phospho-JNK translocation to mitochondria. To compare, AMAP toxicity was assessed in primary mouse hepatocytes (PMH). No cytotoxicity was observed as indicated by the lack of lactate dehydrogenase release and no PI staining. Furthermore, there was no GSH depletion or mitochondrial dysfunction after AMAP treatment in PMH. Immunoblotting for arylated proteins suggested that AMAP treatment caused extensive mitochondrial protein adduct formation in PHH but not in PMH. In conclusion, AMAP is hepatotoxic in PHH and the mechanism involves the formation of mitochondrial protein adducts and mitochondrial dysfunction. - Highlights: • AMAP induces cell death in primary human hepatocytes (PHH). • AMAP does not cause cell death in primary mouse hepatocytes (PMH). • AMAP leads to mitochondria dysfunction in PHH but not PMH. • Protein adduct formation and dysfunction in mitochondria correlate with toxicity.

Mitochondrial protein adducts formation and mitochondrial dysfunction during N-acetyl-m-aminophenol (AMAP)-induced hepatotoxicity in primary human hepatocytes

Energy Technology Data Exchange (ETDEWEB)

Xie, Yuchao; McGill, Mitchell R.; Du, Kuo; Dorko, Kenneth [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Kumer, Sean C.; Schmitt, Timothy M. [Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Ding, Wen-Xing [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States)

2015-12-01

3′-Hydroxyacetanilide or N-acetyl-meta-aminophenol (AMAP) is generally regarded as a non-hepatotoxic analog of acetaminophen (APAP). Previous studies demonstrated the absence of toxicity after AMAP in mice, hamsters, primary mouse hepatocytes and several cell lines. In contrast, experiments with liver slices suggested that it may be toxic to human hepatocytes; however, the mechanism of toxicity is unclear. To explore this, we treated primary human hepatocytes (PHH) with AMAP or APAP for up to 48 h and measured several parameters to assess metabolism and injury. Although less toxic than APAP, AMAP dose-dependently triggered cell death in PHH as indicated by alanine aminotransferase (ALT) release and propidium iodide (PI) staining. Similar to APAP, AMAP also significantly depleted glutathione (GSH) in PHH and caused mitochondrial damage as indicated by glutamate dehydrogenase (GDH) release and the JC-1 assay. However, unlike APAP, AMAP treatment did not cause relevant c-jun-N-terminal kinase (JNK) activation in the cytosol or phospho-JNK translocation to mitochondria. To compare, AMAP toxicity was assessed in primary mouse hepatocytes (PMH). No cytotoxicity was observed as indicated by the lack of lactate dehydrogenase release and no PI staining. Furthermore, there was no GSH depletion or mitochondrial dysfunction after AMAP treatment in PMH. Immunoblotting for arylated proteins suggested that AMAP treatment caused extensive mitochondrial protein adduct formation in PHH but not in PMH. In conclusion, AMAP is hepatotoxic in PHH and the mechanism involves the formation of mitochondrial protein adducts and mitochondrial dysfunction. - Highlights: • AMAP induces cell death in primary human hepatocytes (PHH). • AMAP does not cause cell death in primary mouse hepatocytes (PMH). • AMAP leads to mitochondria dysfunction in PHH but not PMH. • Protein adduct formation and dysfunction in mitochondria correlate with toxicity.

Nuclear-Encoded Mitochondrial mRNAs: A Powerful Force in Axonal Growth and Development.

Science.gov (United States)

Gale, Jenna R; Aschrafi, Armaz; Gioio, Anthony E; Kaplan, Barry B

2018-04-01

Axons, their growth cones, and synaptic nerve terminals are neuronal subcompartments that have high energetic needs. As such, they are enriched in mitochondria, which supply the ATP necessary to meet these demands. To date, a heterogeneous population of nuclear-encoded mitochondrial mRNAs has been identified in distal axons and growth cones. Accumulating evidence suggests that the local translation of these mRNAs is required for mitochondrial maintenance and axonal viability. Here, we review evidence that suggests a critical role for axonal translation of nuclear-encoded mitochondrial mRNAs in axonal growth and development. Additionally, we explore the role that site-specific translation at the mitochondria itself may play in this process. Finally, we briefly review the clinical implications of dysregulation of local translation of mitochondrial-related mRNAs in neurodevelopmental disorders.

Incidence, aetiology and prevention of musculoskeletal injuries in volleyball : A systematic review of the literature

NARCIS (Netherlands)

Kilic, O.; Maas, M.; Verhagen, E.; Zwerver, J.; Gouttebarge, V.

2017-01-01

Currently, there is no overview of the incidence and (volleyball-specific) risk factors of musculoskeletal injuries among volleyball players, nor any insight into the effect of preventive measures on the incidence of injuries in volleyball. This study aimed to review systematically the scientific

Incidence, aetiology and prevention of musculoskeletal injuries in volleyball: A systematic review of the literature

NARCIS (Netherlands)

Kilic, O.; Maas, M.; Verhagen, E.; Zwerver, J.; Gouttebarge, V.

2017-01-01

Currently, there is no overview of the incidence and (volleyball-specific) risk factors of musculoskeletal injuries among volleyball players, nor any insight into the effect of preventive measures on the incidence of injuries in volleyball. This study aimed to review systematically the scientific

Autism in the Son of a Woman with Mitochondrial Myopathy and Dysautonomia: A Case Report.

Science.gov (United States)

Brown, Bradley D; Rais, Theodore

2015-01-01

The relationship between autism spectrum disorders and mitochondrial dysfunction, including mitochondrial myopathies and other mitochondrial diseases, is an area of ongoing research. All autism spectrum disorders are known to be heritable, via genetic and/or epigenetic mechanisms, but specific modes of inheritance are not well characterized. Nevertheless, autism spectrum disorders have been linked to many specific genes associated with mitochondrial function, especially to genes involved in mitochondrial tRNA and the electron transport chain, both particularly vulnerable to point mutations, and clinical research also supports a relationship between the two pathologies. Although only a small minority of patients with autism have a mitochondrial disease, many patients with mitochondrial myopathies have autism spectrum disorder symptoms, and these symptoms may be the presenting symptoms, which presents a diagnostic challenge for clinicians. The authors report the case of a 15-year-old boy with a history of autism spectrum disorder and neurocardiogenic syncope, admitted to the inpatient unit for self-injury, whose young mother, age 35, was discovered to suffer from mitochondrial myopathy, dysautonomia, neurocardiogenic syncope, Ehler-Danlos syndrome, and other uncommon multisystem pathologies likely related to mitochondrial dysfunction. This case illustrates the need for a high index of suspicion for mitochondrial disease in patients with autism, as they have two orders of magnitude greater risk for such diseases than the general population. The literature shows that mitochondrial disease is underdiagnosed in autism spectrum disorder patients and should not be viewed as a "zebra" (i.e., an obscure diagnosis that is made when a more common explanation is more likely).

Biogenesis of mitochondrial carrier proteins: molecular mechanisms of import into mitochondria.

Science.gov (United States)

Ferramosca, Alessandra; Zara, Vincenzo

2013-03-01

Mitochondrial metabolite carriers are hydrophobic proteins which catalyze the flux of several charged or hydrophilic substrates across the inner membrane of mitochondria. These proteins, like most mitochondrial proteins, are nuclear encoded and after their synthesis in the cytosol are transported into the inner mitochondrial membrane. Most metabolite carriers, differently from other nuclear encoded mitochondrial proteins, are synthesized without a cleavable presequence and contain several, poorly characterized, internal targeting signals. However, an interesting aspect is the presence of a positively charged N-terminal presequence in a limited number of mitochondrial metabolite carriers. Over the last few years the molecular mechanisms of import of metabolite carrier proteins into mitochondria have been thoroughly investigated. This review summarizes the present knowledge and discusses recent advances on the import and sorting of mitochondrial metabolite carriers. Copyright © 2012 Elsevier B.V. All rights reserved.

Psychological interventions used to reduce sports injuries: a systematic review of real-world effectiveness.

Science.gov (United States)

Gledhill, Adam; Forsdyke, Dale; Murray, Eliot

2018-02-20

To systematically review studies examining the role of psychological interventions in injury prevention. The primary research question was: What is the real-world effectiveness of psychological intervention in preventing sports injuries? Mixed methods systematic review with best evidence synthesis. CINAHL, MEDLINE, PsycARTICLES, PsycINFO, SPORTDiscus, Science Direct and PubMed. Randomised controlled trials (RCT), non-RCTs that included a comparison group, before and after study designs and qualitative methods. Studies were required to outline specific unimodal or multimodal psychological interventions used in relation to injury prevention in the real-world setting. Studies were independently appraised with the Mixed Methods Appraisal Tool. Thirteen papers (incorporating 14 studies) met the eligibility criteria, of which 93% (13/14) reported a decrease in injury rates (effect size range=0.2-1.21). There was an overall moderate risk of bias in reporting (52%). There is a dominance of stress management-based interventions in literature due to the prominence of the model of stress and athletic injury within the area. Psychological interventions demonstrate small (0.2) to large (1.21) effects on sports injury rates. The research area demonstrates a cumulative moderate risk in reporting bias (52%). CRD42016035879. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Protection against oxidant-induced apoptosis by mitochondrial thioredoxin in SH-SY5Y neuroblastoma cells

International Nuclear Information System (INIS)

Chen Yan; Yu Min; Jones, Dean P.; Greenamyre, J. Timothy; Cai Jiyang

2006-01-01

Mitochondrial oxidative stress plays important roles in aging and age-related degenerative disorders. The newly identified mitochondrial thioredoxin (mtTrx; Trx2) is a key component of the mitochondrial antioxidant system which is responsible for the clearance of reactive intermediates and repairs proteins with oxidative damage. Here, we show that in cultured SH-SY5Y human neuroblastoma 1cells, overexpression of mtTrx inhibited apoptosis and loss of mitochondrial membrane potential induced by a chemical oxidant, tert-butylhydroperoxide (tBH). The effects of calcium ionophore (Br-A23187) were not affected by mtTrx, suggesting the protection was specific against oxidative injury. The mitochondrial glutathione pool was oxidized by tBH, and this oxidation was not inhibited by increased mtTrx. Consequently, the antioxidant function of mtTrx is not redundant, but rather in addition, to that of GSH. Mutations of Cys90 and Cys93 to serines rendered mtTrx ineffective in protection against tBH-induced cytoxicity. These data indicate that mtTrx controls the mitochondrial redox status independently of GSH and is a key component of the defensive mechanism against oxidative stress in cultured neuronal cells

The effect of aging on mitochondrial proteins in germinating soybean embryonic axes

International Nuclear Information System (INIS)

Furman, K.C.

1988-01-01

Aging-induced deterioration is a major problem associated with seed storage. Impairment of mitochondrial function is one of the first effects of aging. The composition and synthesis of nuclear and mito-coded mitochondrial proteins from soybean (Glycine max. L. Merr.) embryonic axes were studied to elucidate the cause of impaired respiratory development during germination of aged seeds. Axes excised from high vigor (HV) seeds and aged or low vigor (LV) seeds were protected from imbibition injury and germinated for various times, or excised from developing seeds, and then radiolabeled for one hour in [ 35 S]methionine. Mitochondria were then isolated and total mitochondrial protein was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), followed by quantitative staining and fluorography of labeled polypeptides. Alternatively, an original two-dimensional native-to-denaturing gel electrophoretic technique was used to analyze native protein associations and to purify a 23 kD polypeptide

Methods of analysis of physical activity among persons with spinal cord injury: A review

OpenAIRE

Jarmila Štěpánová; Martin Kudláček; Mirka Bednaříková

2016-01-01

Background: A spinal cord injury is one of the most devastating acquired physical disabilities. People with spinal cord injury are usually in a productive age, often interested in sports and physical activity. Therefore it is essential to support the development of monitoring of the quality and quantity of physical activity of people with spinal cord injury. Objective: The aim of this study was to perform systematic review of international studies from the period 2004-2014 with the aim to fin...

Incidence of Traumatic Brain Injury Across the Full Disease Spectrum: A Population-Based Medical Record Review Study

Science.gov (United States)

Leibson, Cynthia L.; Brown, Allen W.; Ransom, Jeanine E.; Diehl, Nancy N.; Perkins, Patricia K.; Mandrekar, Jay; Malec, James F.

2012-01-01

Background Extremely few objective estimates of traumatic brain injury incidence include all ages, both sexes, all injury mechanisms, and the full spectrum from very mild to fatal events. Methods We used unique Rochester Epidemiology Project medical records-linkage resources, including highly sensitive and specific diagnostic coding, to identify all Olmsted County, MN, residents with diagnoses suggestive of traumatic brain injury regardless of age, setting, insurance, or injury mechanism. Provider-linked medical records for a 16% random sample were reviewed for confirmation as definite, probable, possible (symptomatic), or no traumatic brain injury. We estimated incidence per 100,000 person-years for 1987–2000 and compared these record-review rates with rates obtained using Centers for Disease Control and Prevention (CDC) data-systems approach. For the latter, we identified all Olmsted County residents with any CDC-specified diagnosis codes recorded on hospital/emergency department administrative claims or death certificates 1987–2000. Results Of sampled individuals, 1257 met record-review criteria for incident traumatic brain injury; 56% were ages 16–64 years, 56% were male, 53% were symptomatic. Mechanism, sex, and diagnostic certainty differed by age. The incidence rate per 100,000 person-years was 558 (95% confidence interval = 528–590) versus 341 (331–350) using the CDC data system approach. The CDC approach captured only 40% of record-review cases. Seventy-four percent of missing cases presented to hospital/emergency department; none had CDC-specified codes assigned on hospital/emergency department administrative claims or death certificates; 66% were symptomatic. Conclusions Capture of symptomatic traumatic brain injuries requires a wider range of diagnosis codes, plus sampling strategies to avoid high rates of false-positive events. PMID:21968774

SMG-1 kinase attenuates mitochondrial ROS production but not cell respiration deficits during hyperoxia.

Science.gov (United States)

Resseguie, Emily A; Brookes, Paul S; O'Reilly, Michael A

Supplemental oxygen (hyperoxia) used to treat individuals in respiratory distress causes cell injury by enhancing the production of toxic reactive oxygen species (ROS) and inhibiting mitochondrial respiration. The suppressor of morphogenesis of genitalia (SMG-1) kinase is activated during hyperoxia and promotes cell survival by phosphorylating the tumor suppressor p53 on serine 15. Here, we investigate whether SMG-1 and p53 blunt this vicious cycle of progressive ROS production and decline in mitochondrial respiration seen during hyperoxia. Human lung adenocarcinoma A549 and H1299 or colon carcinoma HCT116 cells were depleted of SMG-1, UPF-1, or p53 using RNA interference, and then exposed to room air (21% oxygen) or hyperoxia (95% oxygen). Immunoblotting was used to evaluate protein expression; a Seahorse Bioanalyzer was used to assess cellular respiration; and flow cytometry was used to evaluate fluorescence intensity of cells stained with mitochondrial or redox sensitive dyes. Hyperoxia increased mitochondrial and cytoplasmic ROS and suppressed mitochondrial respiration without changing mitochondrial mass or membrane potential. Depletion of SMG-1 or its cofactor, UPF1, significantly enhanced hyperoxia-induced mitochondrial but not cytosolic ROS abundance. They did not affect mitochondrial mass, membrane potential, or hyperoxia-induced deficits in mitochondrial respiration. Genetic depletion of p53 in A549 cells and ablation of the p53 gene in H1299 or HCT116 cells revealed that SMG-1 influences mitochondrial ROS through activation of p53. Our findings show that hyperoxia does not promote a vicious cycle of progressive mitochondrial ROS and dysfunction because SMG-1-p53 signaling attenuates production of mitochondrial ROS without preserving respiration. This suggests antioxidant therapies that blunt ROS production during hyperoxia may not suffice to restore cellular respiration.

Risk factors for musculoskeletal injury in preprofessional dancers: a systematic review.

Science.gov (United States)

Kenny, Sarah J; Whittaker, Jackie L; Emery, Carolyn A

2016-08-01

Preprofessional dancers partake in rigorous training and have high injury prevalence. Attempts to identify risk factors for dance injuries have focused on a diversity of intrinsic and extrinsic factors. To identify and evaluate the evidence examining risk factors for musculoskeletal injury in preprofessional ballet and modern dancers. Fifteen electronic databases were systematically searched to October 2015. Studies selected met a priori inclusion criteria and investigated musculoskeletal injury risk factors in preprofessional (elite adolescent, student, young adult) ballet and modern dancers. Two reviewers independently assessed the quality and level of evidence using the Downs and Black (DB) criteria and a modified Oxford Centre of Evidence-Based Medicine 2009 model, respectively. Of 1364 potentially relevant studies, 47 were included and scored. Inconsistent injury definition and methodology precluded meta-analysis. The most common modifiable risk factors investigated were anthropometrics (ie, body mass index, adiposity), joint range of motion (ie, lower extremity), dance exposure (ie, years training, exposure hours) and age. The median DB score across studies was 8/33 (range 2-16). The majority of studies were classified as level 3 evidence and few considered risk factor inter-relationships. There is some level 2 evidence that previous injury and poor psychological coping skills are associated with increased injury risk. Because of the lack of high-quality studies, consensus regarding risk factors for musculoskeletal injury in preprofessional dancers remains difficult. There is a need for injury definition consensus and high-quality prospective studies examining the multifactorial relationship between risk factors and injury in preprofessional dance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Peripheral neuropathy associated with mitochondrial disease in children.

Science.gov (United States)

Menezes, Manoj P; Ouvrier, Robert A

2012-05-01

Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

CoMIC, the hidden dynamics of mitochondrial inner compartments.

Science.gov (United States)

Cho, Bongki; Sun, Woong

2017-12-01

Mitochondria have evolutionarily, functionally and structurally distinct outer- (OMM) and inner-membranes (IMM). Thus, mitochondrial morphology is controlled by independent but coordinated activity of fission and fusion of the OMM and IMM. Constriction and division of the OMM are mediated by endocytosis-like machineries, which include dynamin-related protein 1 with additional cytosolic vesicle scissoring machineries such as actin filament and Dynamin 2. However, structural alteration of the IMM during mitochondrial division has been poorly understood. Recently, we found that the IMM and the inner compartments undergo transient and reversible constriction prior to the OMM division, which we termed CoMIC, Constriction of Mitochondrial Inner Compartment. In this short review, we further discuss the evolutionary perspective and the regulatory mechanism of CoMIC during mitochondrial division. [BMB Reports 2017; 50(12): 597-598].

Pediatric Lower Extremity Lawn Mower Injuries and Reconstruction: Retrospective 10-Year Review at a Level 1 Trauma Center.

Science.gov (United States)

Branch, Leslie G; Crantford, John C; Thompson, James T; Tannan, Shruti C

2017-11-01

From 2004 to 2013, there were 9341 lawn mower injuries in children under 20 years old. The incidence of lawn mower injuries in children has not decreased since 1990 despite implementation of various different prevention strategies. In this report, the authors review the results of pediatric lawn mower-related lower-extremity injuries treated at a tertiary care referral center as well as review the overall literature. A retrospective review was performed at a level 1 trauma center over a 10-year period (2005-2015). Patients younger than 18 years who presented to the emergency room with lower extremity lawn mower injuries were included. Of the 27 patients with lower-extremity lawn mower injuries during this period, the mean age at injury was 5.5 years and Injury Severity Score was 7.2. Most (85%) patients were boys and the predominant type of mower causing injury was a riding lawn mower (96%). Injury occurred in patients who were bystanders in 78%, passengers in 11%, and operators in 11%. Mean length of stay was 12.2 days, and mean time to reconstruction was 7.9 days. Mean number of surgical procedures per patient was 4.1. Amputations occurred in 15 (56%) cases with the most common level of amputation being distal to the metatarsophalangeal joint (67%). Reconstructive procedures ranged from direct closure (41%) to free tissue transfer (7%). Major complications included infection (7%), wound dehiscence (11%), and delayed wound healing (15%). Mean follow up was 23.6 months and 100% of the patients were ambulatory after injury. The subgroup of patients with the most severe injuries, highest number of amputations, and need for overall surgical procedures were patients aged 2 to 5 years. A review of the literature also showed consistent findings. This study demonstrates the danger and morbidity that lawn mowers present to the pediatric population, particularly children aged 2 to 5 years. Every rung of the so-called reconstructive ladder is used in caring for these

Hydralazine inhibits compression and acrolein-mediated injuries in ex vivo spinal cord.

Science.gov (United States)

Hamann, Kristin; Nehrt, Genevieve; Ouyang, Hui; Duerstock, Brad; Shi, Riyi

2008-02-01

We have previously shown that acrolein, a lipid peroxidation byproduct, is significantly increased following spinal cord injury in vivo, and that exposure to neuronal cells results in oxidative stress, mitochondrial dysfunction, increased membrane permeability, impaired axonal conductivity, and eventually cell death. Acrolein thus may be a key player in the pathogenesis of spinal cord injury, where lipid peroxidation is known to be involved. The current study demonstrates that the acrolein scavenger hydralazine protects against not only acrolein-mediated injury, but also compression in guinea pig spinal cord ex vivo. Specifically, hydralazine (500 mumol/L to 1 mmol/L) can significantly alleviate acrolein (100-500 mumol/L)-induced superoxide production, glutathione depletion, mitochondrial dysfunction, loss of membrane integrity, and reduced compound action potential conduction. Additionally, 500 mumol/L hydralazine significantly attenuated compression-mediated membrane disruptions at 2 and 3 h following injury. This was consistent with our findings that acrolein-lys adducts were increased following compression injury ex vivo, an effect that was prevented by hydralazine treatment. These findings provide further evidence for the role of acrolein in spinal cord injury, and suggest that acrolein-scavenging drugs such as hydralazine may represent a novel therapy to effectively reduce oxidative stress in disorders such as spinal cord injury and neurodegenerative diseases, where oxidative stress is known to play a role.

Sport psychology education for sport injury rehabilitation professionals: a systematic review.

Science.gov (United States)

Heaney, Caroline A; Walker, Natalie C; Green, Alison J K; Rostron, Claire L

2015-02-01

Sport psychology education has been shown to have a positive impact on the practice of sport injury rehabilitation professionals (SIRPs). The purpose of this paper is to review recommendations relating to such education. The paper presents a review of existing literature relating to the content and mode of delivery for a sport psychology education programme for SIRPs. The review seeks to address four questions: (1) What topic areas do researchers suggest should be integrated into the sport psychology education of SIRPs? (2) What topic areas are currently being recommended by professional bodies? (3) What are the findings of research examining the impact of sport psychology education on SIRPs? and (4) What do researchers recommend to be the most appropriate mode of delivery for sport psychology education for SIRPs? The findings of the review suggest that in order to maximise adherence amongst already qualified SIRPs sport psychology education should be delivered in a flexible short duration package. Additionally three broad areas that sport psychology education should cover emerged: (1) understanding of the psychological impact of injury, (2) interventions and psychological skills/techniques, and (3) referral and professional boundaries. This has important implications for the future training of SIRPs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Renal transplantation induces mitochondrial uncoupling, increased kidney oxygen consumption, and decreased kidney oxygen tension

NARCIS (Netherlands)

Papazova, Diana A.; Friederich-Persson, Malou; Joles, Jaap A.; Verhaar, Marianne C.

2015-01-01

Hypoxia is an acknowledged pathway to renal injury and ischemia-reperfusion (I/R) and is known to reduce renal oxygen tension (PO2). We hypothesized that renal I/R increases oxidative damage and induces mitochondrial uncoupling, resulting in increased oxygen consumption and hence kidney

Sport-related structural brain injury associated with arachnoid cysts: a systematic review and quantitative analysis.

Science.gov (United States)

Zuckerman, Scott L; Prather, Colin T; Yengo-Kahn, Aaron M; Solomon, Gary S; Sills, Allen K; Bonfield, Christopher M

2016-04-01

OBJECTIVE Arachnoid cysts (ACs) are congenital lesions bordered by an arachnoid membrane. Researchers have postulated that individuals with an AC demonstrate a higher rate of structural brain injury after trauma. Given the potential neurological consequences of a structural brain injury requiring neurosurgical intervention, the authors sought to perform a systematic review of sport-related structural-brain injury associated with ACs with a corresponding quantitative analysis. METHODS Titles and abstracts were searched systematically across the following databases: PubMed, Embase, CINAHL, and PsycINFO. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Peer-reviewed case reports, case series, or observational studies that reported a structural brain injury due to a sport or recreational activity (hereafter referred to as sport-related) with an associated AC were included. Patients were excluded if they did not have an AC, suffered a concussion without structural brain injury, or sustained the injury during a non-sport-related activity (e.g., fall, motor vehicle collision). Descriptive statistical analysis and time to presentation data were summarized. Univariate logistic regression models to assess predictors of neurological deficit, open craniotomy, and cystoperitoneal shunt were completed. RESULTS After an initial search of 994 original articles, 52 studies were found that reported 65 cases of sport-related structural brain injury associated with an AC. The median age at presentation was 16 years (range 4-75 years). Headache was the most common presenting symptom (98%), followed by nausea and vomiting in 49%. Thirteen patients (21%) presented with a neurological deficit, most commonly hemiparesis. Open craniotomy was the most common form of treatment (49%). Bur holes and cyst fenestration were performed in 29 (45%) and 31 (48%) patients, respectively. Seven patients (11%) received

Do runners who suffer injuries have higher vertical ground reaction forces than those who remain injury-free? A systematic review and meta-analysis

NARCIS (Netherlands)

van der Worp, Henk; Vrielink, Jelte W.; Bredeweg, Steef W.

2016-01-01

Background Vertical ground reaction force (VGRF) parameters have been implicated as a cause of several running-related injuries. However, no systematic review has examined this relationship. Aim We systematically reviewed evidence for a relation between VGRF parameters and specific running-related

Mitochondrial cardiomyopathies

Directory of Open Access Journals (Sweden)

Ayman W. El-Hattab

2016-07-01

Full Text Available Mitochondria are found in all nucleated human cells and perform a variety of essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA while more than 99% of them are encoded by nuclear DNA (nDNA. Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs of various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20-40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular noncompaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain (ETC complexes subunits and their assembly factors, mitochondrial tRNAs, rRNAs, ribosomal proteins, and translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia.

Platelet-rich plasma (PRP for acute muscle injury: a systematic review.

Directory of Open Access Journals (Sweden)

Mohamad Shariff A Hamid

Full Text Available INTRODUCTION: Acute muscle injury is one of the commonest injuries that often result in loss of training and competition time. The best management for muscle injury has not been identified. Sports medicine practitioners used several approaches in attempt to accelerate time to recovery from muscle injury. More recently growing interest focussed on autologous blood product injection. METHODS: A literature search was conducted systematically using OvidMEDLINE, PubMed, EMBASE, SPORTDiscus and CINAHL databases to retrieve articles published until December 2012. Controlled trials and controlled laboratory studies comparing different strategies to promote early recovery of muscle injury were included. The methodological quality of studies was assessed. RESULTS: There are limited studies on the effects of PRP therapy for muscle injury. Three in vivo laboratory studies and one pilot human study were reviewed. The laboratory studies reported histological evidence on significant acceleration of muscle healing in animals treated with autologous conditioned serum (ACS, platelet-rich plasma (PRP and platelet rich fibrin matrix (PRFM. A pilot human study found athletes treated with repeated ACS injection recovers significantly faster than retrospective controls. CONCLUSION: Several in vivo laboratory studies suggest beneficial effects of ACS, PRP and PRFM in accelerating muscle recovery. Evidence to suggest similar effects on humans is however limited, as valuable information from robust human controlled trials is still not available at this moment. Hence, more studies of satisfactory methodological quality with platelet-rich plasma interventions on muscle injury are justified.

The prognostic value of MRI in determining reinjury risk following acute hamstring injury: a systematic review.

Science.gov (United States)

van Heumen, Moniek; Tol, Johannes L; de Vos, Robert-Jan; Moen, Maarten H; Weir, Adam; Orchard, John; Reurink, Gustaaf

2017-09-01

A challenge for sports physicians is to estimate the risk of a hamstring re-injury, but the current evidence for MRI variables as a risk factor is unknown. To systematically review the literature on the prognostic value of MRI findings at index injury and/or return to play for acute hamstring re-injuries. Databases of PubMed, Embase, MEDLINE, Scopus, CINAHL, Google Scholar, Web of Science, LILACS, SciELO, ScienceDirect, ProQuest, SPORTDiscus and Cochrane Library were searched until 20 June 2016. Studies evaluating MRI as a prognostic tool for determining the risk of re-injury for athletes with acute hamstring injuries were eligible for inclusion. Two authors independently screened the search results and assessed risk of bias using standardised criteria from a consensus statement. A best-evidence synthesis was used to identify the level of evidence. Post hoc analysis included correction for insufficient sample size. Of the 11 studies included, 7 had a low and 4 had a high risk of bias. No strong evidence for any MRI finding as a risk factor for hamstring re-injury was found. There was moderate evidence that intratendinous injuries were associated with increased re-injury risk. Post hoc analysis showed moderate evidence that injury to the biceps femoris was a moderate to strong risk factor for re-injury. There is currently no strong evidence for any MRI finding in predicting hamstring re-injury risk. Intratendinous injuries and biceps femoris injuries showed moderate evidence for association with a higher re-injury risk. Registration in the PROSPERO International prospective register of systematic reviews was performed prior to study initiation (registration number CRD42015024620). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

International Nuclear Information System (INIS)

Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

2009-01-01

Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

Physiotherapy after traumatic brain injury: a systematic review of the literature.

Science.gov (United States)

Hellweg, Stephanie; Johannes, Sönke

2008-05-01

At present there are no standardized recommendations concerning physiotherapy of individuals with traumatic brain injury (TBI) resulting in a high variability of methods and intensity. The aim of this literature review is to develop recommendations concerning physiotherapy in the post-acute phase after TBI on the basis of scientific evidence. literature review: data bases: PubMed, PEDro, OT-Seeker, Cochrane and Cinahl. brain injury (in PEDro, OT-Seeker, Cochrane), brain injury AND physical therapy (in PubMed and Cinahl). Fourteen studies met the inclusion criteria and were grouped into sub-groups: sensory stimulation, therapy intensity, casting/splinting, exercise or aerobic training and functional skill training. While for sensory stimulation evidence could not be proven, a strong evidence exists that more intensive rehabilitation programmes lead to earlier functional abilities. The recommendation due to casting for the improvement of passive range of motion is a grade B, while only a C recommendation is appropriate concerning tonus reduction. Strong evidence exists that intensive task-orientated rehabilitation programmes lead to earlier and better functional abilities. Although some recommendations for the effectiveness of physical therapy interventions could be expressed, there are many questions concerning the treatment of humans with TBI which have not been investigated so far. Especially on the level of activity and participation only a few studies exist.

Current perspectives on mitochondrial inheritance in fungi

Directory of Open Access Journals (Sweden)

Xu J

2015-08-01

Full Text Available Jianping Xu,1,2 He Li2 1Department of Biology, McMaster University, Hamilton, Canada; 2The Key Laboratory for Non-Wood Forest Cultivation and Conservation of the Federal Ministry of Education, Central South University of Forestry and Technology, Changsha, People’s Republic of China Abstract: The mitochondrion is an essential organelle of eukaryotes, generating the universal energy currency, adenosine triphosphate, through oxidative phosphorylation. However, aside from generation of adenosine triphosphate, mitochondria have also been found to impact a diversity of cellular functions and organ system health in humans and other eukaryotes. Thus, inheriting and maintaining functional mitochondria are essential for cell health. Due to the relative ease of conducting genetic and molecular biological experiments using fungi, they (especially the budding yeast Saccharomyces cerevisiae have been used as model organisms for investigating the patterns of inheritance and intracellular dynamics of mitochondria and mitochondrial DNA. Indeed, the diversity of mitochondrial inheritance patterns in fungi has contributed to our broad understanding of the genetic, cellular, and molecular controls of mitochondrial inheritance and their evolutionary implications. In this review, we briefly summarize the patterns of mitochondrial inheritance in fungi, describe the genes and processes involved in controlling uniparental mitochondrial DNA inheritance in sexual crosses in basidiomycete yeasts, and provide an overview of the molecular and cellular processes governing mitochondrial inheritance during asexual budding in S. cerevisiae. Together, these studies reveal that complex regulatory networks and molecular processes are involved in ensuring the transmission of healthy mitochondria to the progeny. Keywords: uniparental inheritance, biparental inheritance, mating type, actin cable, mitochore, mitochondrial partition 

Caregiver outcomes and interventions: a systematic scoping review of the traumatic brain injury and spinal cord injury literature.

Science.gov (United States)

Baker, Anne; Barker, Samantha; Sampson, Amanda; Martin, Clarissa

2017-01-01

To identify factors reported with negative and positive outcomes for caregivers of the traumatic brain injury and spinal cord injury cohorts, to investigate what interventions have been studied to support carers and to report what effectiveness has been found. Scoping systematic review. Electronic databases and websites were searched from 1990 to December 2015. Studies were agreed for inclusion using pre-defined criteria. Relevant information from included studies was extracted and quality assessment was completed. Data were synthesised using qualitative methods. A total of 62 studies reported caregiver outcomes for the traumatic brain injury cohort; 51 reported negative outcomes and 11 reported positive outcomes. For the spinal cord injury cohort, 18 studies reported caregiver outcomes; 15 reported negative outcomes and three reported positive outcomes. Burden of care was over-represented in the literature for both cohorts, with few studies looking at factors associated with positive outcomes. Good family functioning, coping skills and social support were reported to mediate caregiver burden and promote positive outcomes. A total of 21 studies further described interventions to support traumatic brain injury caregivers and four described interventions to support spinal cord injury caregivers, with emerging evidence for the effectiveness of problem-solving training. Further research is required to explore the effects of injury severity of the care recipient, as well as caregiver age, on the outcome of the interventions. Most studies reported negative outcomes, suggesting that barriers to caregiving have been established, but not facilitators. The interventions described to support carers are limited and require further testing to confirm their effectiveness.

Muscle Mitochondrial Uncoupling Dismantles Neuromuscular Junction and Triggers Distal Degeneration of Motor Neurons

Science.gov (United States)

Dupuis, Luc; Gonzalez de Aguilar, Jose-Luis; Echaniz-Laguna, Andoni; Eschbach, Judith; Rene, Frédérique; Oudart, Hugues; Halter, Benoit; Huze, Caroline; Schaeffer, Laurent; Bouillaud, Frédéric; Loeffler, Jean-Philippe

2009-01-01

Background Amyotrophic lateral sclerosis (ALS), the most frequent adult onset motor neuron disease, is associated with hypermetabolism linked to defects in muscle mitochondrial energy metabolism such as ATP depletion and increased oxygen consumption. It remains unknown whether muscle abnormalities in energy metabolism are causally involved in the destruction of neuromuscular junction (NMJ) and subsequent motor neuron degeneration during ALS. Methodology/Principal Findings We studied transgenic mice with muscular overexpression of uncoupling protein 1 (UCP1), a potent mitochondrial uncoupler, as a model of muscle restricted hypermetabolism. These animals displayed age-dependent deterioration of the NMJ that correlated with progressive signs of denervation and a mild late-onset motor neuron pathology. NMJ regeneration and functional recovery were profoundly delayed following injury of the sciatic nerve and muscle mitochondrial uncoupling exacerbated the pathology of an ALS animal model. Conclusions/Significance These findings provide the proof of principle that a muscle restricted mitochondrial defect is sufficient to generate motor neuron degeneration and suggest that therapeutic strategies targeted at muscle metabolism might prove useful for motor neuron diseases. PMID:19404401

Mitochondrial function, ornamentation, and immunocompetence.

Science.gov (United States)

Koch, Rebecca E; Josefson, Chloe C; Hill, Geoffrey E

2017-08-01

Understanding the mechanisms that link ornamental displays and individual condition is key to understanding the evolution and function of ornaments. Immune function is an aspect of individual quality that is often associated with the expression of ornamentation, but a general explanation for why the expression of some ornaments seems to be consistently linked to immunocompetence remains elusive. We propose that condition-dependent ornaments may be linked to key aspects of immunocompetence through co-dependence on mitochondrial function. Mitochondrial involvement in immune function is rarely considered outside of the biomedical literature, but the role of mitochondria as the primary energy producers of the cell and the centres of biosynthesis, the oxidative stress response, and cellular signalling place them at the hub of a variety of immune pathways. A promising new mechanistic explanation for correlations between a wide range of ornamental traits and the properties of individual quality is that mitochondrial function may be the 'shared pathway' responsible for links between ornament production and individual condition. Herein, we first review the role of mitochondria as both signal transducers and metabolic regulators of immune function. We then describe connections between hormonal pathways and mitochondria, with implications for both immune function and the expression of ornamentation. Finally, we explore the possibility that ornament expression may link directly to mitochondrial function. Considering condition-dependent traits within the framework of mitochondrial function has the potential to unify central tenets within the study of sexual selection, eco-immunology, oxidative stress ecology, stress and reproductive hormone biology, and animal physiology. © 2016 Cambridge Philosophical Society.

Roles of Mitochondrial DNA Mutations in Stem Cell Ageing

Directory of Open Access Journals (Sweden)

Tianhong Su

2018-03-01

Full Text Available Mitochondrial DNA (mtDNA mutations accumulate in somatic stem cells during ageing and cause mitochondrial dysfunction. In this review, we summarize the studies that link mtDNA mutations to stem cell ageing. We discuss the age-related behaviours of the somatic mtDNA mutations in stem cell populations and how they potentially contribute to stem cell ageing by altering mitochondrial properties in humans and in mtDNA-mutator mice. We also draw attention to the diverse fates of the mtDNA mutations with different origins during ageing, with potential selective pressures on the germline inherited but not the somatic mtDNA mutations.

Supplemental surveillance: a review of 2015 and 2016 agricultural injury data from news reports on AgInjuryNews.org.

Science.gov (United States)

Weichelt, Bryan; Gorucu, Serap

2018-01-31

Agriculture, forestry, fishing and hunting industry is the most hazardous occupational sector in the USA. Even with this level of occupational risk, several national and state-level occupational injury surveillance programmes have been eliminated, leaving regional efforts to analyse multiple sources and compile data on agricultural injuries and fatalities. No up-to-date centralised national database for agricultural injuries/fatalities in the USA currently exists. Using the public data on AgInjuryNews.org, this study considered a wide range of variables to examine fatalities and injuries of the industry in 2015 and 2016. The results reported in this paper sought to explore and understand common data elements of US news reports. As of 5 April 2017, more than 3000 articles across 36 years were contained in the dataset. We selected 2 years to review, 2015 and 2016, which represented the most complete years to date; 2015 was the first year in which systematic collection was initiated by the AgInjuryNews.org team. Data were coded based on the Occupational Injury and Illness Classification System source and event/exposure types. A total of 1345 victims were involved in 1044 incidents. Leading sources of injuries were vehicles and machinery, and the most common event/exposure type was transportation. This study demonstrated that data from AgInjuryNew.org is consistent with previous literature, and it can supply up-to-date data as an open-source surveillance supplement, disseminated for health and safety stakeholders. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Extrinsic and intrinsic factors associated with non-contact injury in adult pace bowlers: a systematic review protocol.

Science.gov (United States)

Olivier, Benita; Stewart, Aimee; Taljaard, Tracy; Burger, Elaine; Brukner, Peter; Orchard, John; Gray, Janine; Botha, Nadine; Mckinon, Warrick

2015-01-01

Review question: which extrinsic and intrinsic factors are associated with non-contact injury in adult cricket pace bowlers?Review objective: the objective of this review is to determine the extrinsic and intrinsic factors associated with non-contact injury in adult pace bowlers. Cricket is generally considered to be a sport of low injury risk compared to other sports. In cricket, the pace bowler strives towards the adoption of a bowling technique with a relatively low injury threat that will, at the same time, allow for a fast (>120km/hr) and accurate delivery to the opposing batsman. However, of all the various roles of the cricket player, the pace bowler has the highest risk of injury, especially for low back and lower limb (lower quarter) injury. The reason for this high risk of injury is due to the inherent, high-load biomechanical nature of the pace bowling action. The high prevalence of injury amongst pace bowlers highlights the great need for research into factors associated with injury.Both extrinsic and intrinsic factors work in combination to predispose the bowler to injury. Extrinsic or environment-related factors include bowling workload (the numbers of overs a bowler bowls), player position (first, second or third change) and time of play (morning or afternoon). A high bowling workload has been linked with a higher risk of injury in pace bowlers. Foster et al. found in an observational study that bowling too many overs in a single spell or bowling too many spells may increase the pace bowler's risk of sustaining a low back injury. In another observational study, Dennis et al. found that an exceptionally high bowling workload as well as an uncommonly low bowling workload is associated with injury risk. The major extrinsic factors for bowling injury identified by Orchard et al. are a high number of match overs bowled in the previous week, number of days of play and bowling second (batting first) in a match. Extrinsic factors are known to make the bowler