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Sample records for affects cerebral cytochrome

  1. Exposure to GSM 900 MHz electromagnetic fields affects cerebral cytochrome c oxidase activity.

    PubMed

    Ammari, Mohamed; Lecomte, Anthony; Sakly, Mohsen; Abdelmelek, Hafedh; de-Seze, René

    2008-08-19

    The world-wide and rapidly growing use of mobile phones has raised serious concerns about the biological and health-related effects of radio frequency (RF) radiation, particularly concerns about the effects of RFs upon the nervous system. The goal of this study was conducted to measure cytochrome oxidase (CO) levels using histochemical methods in order to evaluate regional brain metabolic activity in rat brain after exposure to a GSM 900 MHz signal for 45 min/day at a brain-averaged specific absorption rate (SAR) of 1.5 W/Kg or for 15 min/day at a SAR of 6 W/Kg over seven days. Compared to the sham and control cage groups, rats exposed to a GSM signal at 6 W/Kg showed decreased CO activity in some areas of the prefrontal and frontal cortex (infralimbic cortex, prelimbic cortex, primary motor cortex, secondary motor cortex, anterior cingulate cortex areas 1 and 2 (Cg1 and Cg2)), the septum (dorsal and ventral parts of the lateral septal nucleus), the hippocampus (dorsal field CA1, CA2 and CA3 of the hippocampus and dental gyrus) and the posterior cortex (retrosplenial agranular cortex, primary and secondary visual cortex, perirhinal cortex and lateral entorhinal cortex). However, the exposure to GSM at 1.5 W/Kg did not affect brain activity. Our results indicate that 6 W/Kg GSM 900 MHz microwaves may affect brain metabolism and neuronal activity in rats.

  2. Human cerebral response to animal affective vocalizations.

    PubMed

    Belin, Pascal; Fecteau, Shirley; Charest, Ian; Nicastro, Nicholas; Hauser, Marc D; Armony, Jorge L

    2008-03-07

    It is presently unknown whether our response to affective vocalizations is specific to those generated by humans or more universal, triggered by emotionally matched vocalizations generated by other species. Here, we used functional magnetic resonance imaging in normal participants to measure cerebral activity during auditory stimulation with affectively valenced animal vocalizations, some familiar (cats) and others not (rhesus monkeys). Positively versus negatively valenced vocalizations from cats and monkeys elicited different cerebral responses despite the participants' inability to differentiate the valence of these animal vocalizations by overt behavioural responses. Moreover, the comparison with human non-speech affective vocalizations revealed a common response to the valence in orbitofrontal cortex, a key component on the limbic system. These findings suggest that the neural mechanisms involved in processing human affective vocalizations may be recruited by heterospecific affective vocalizations at an unconscious level, supporting claims of shared emotional systems across species.

  3. Alleviation of Brain Injury-Induced Cerebral Metabolic Depression by Amphetamine: A Cytochrome Oxidase Histochemistry Study

    PubMed Central

    Sutton, Richard L.; Hovda, David A.; Chen, Michael J.; Feeney, Dennis M.

    2000-01-01

    Measurements of oxidative metabolic capacity following the ablation of rat sensorimotor cortex and ,he administration of amphetamine were examined to determine their effects on the metabolic dysfunction that follows brain injury. Twenty-four hours after surgery, rats sustaining either sham operations or unilateral cortical ablation were administered a single injection of D-amphetamine (2 mg/kg; i.p.) or saline and then sacrificed 24 h later. Brain tissue was processed for cytochrome oxidase histochemistry, and 12 bilateral cerebral areas were measured, using optical density as an index of the relative amounts of the enzyme. Compared with that of the control groups, cytochrome oxidase in the injured animals was significantly reduced throughout the cerebral cortex and in 5 of II subcortical structures. This injury-induced depression of oxidative capacity was most pronounced in regions of the hemisphere ipsilateral to the ablation. Animals given D-amphetamine had less depression of oxidative capacity, which was most pronounced bilaterally in the cerebral cortex, red nucleus, and superior colliculus; and in the nucleus accumbens, caudateputamen, and globus pallidus ipsilaterai to the ablation. The ability of D-amphetamine to alleviate depressed cerebral oxidative metabolism following cortical injury may be one mechanism by which drugs increasing noradrenaline release accelerate functional recovery in both animals and humans. PMID:10709218

  4. Responsiveness of cerebral and hepatic cytochrome P450s in rat offspring prenatally exposed to lindane

    SciTech Connect

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

    2008-08-15

    ABSTRACT: Prenatal exposure to low doses of lindane has been shown to affect the ontogeny of xenobiotic metabolizing cytochrome P450s (CYPs), involved in the metabolism and neurobehavioral toxicity of lindane. Attempts were made in the present study to investigate the responsiveness of CYPs in offspring prenatally exposed to lindane (0.25 mg/kg b. wt.; 1/350th of LD{sub 50}; p. o. to mother) when challenged with 3-methylcholanthrene (MC) or phenobarbital (PB), inducers of CYP1A and 2B families or a sub-convulsant dose of lindane (30 mg/kg b. wt., p. o.) later in life. Prenatal exposure to lindane was found to produce an increase in the mRNA and protein expression of CYP1A1, 1A2, 2B1, 2B2 isoforms in brain and liver of the offspring at postnatal day 50. The increased expression of the CYPs in the offspring suggests the sensitivity of the CYPs during postnatal development, possibly, to low levels of lindane, which may partition into mother's milk. A higher increase in expression of CYP1A and 2B isoenzymes and their catalytic activity was observed in animals pretreated prenatally with lindane and challenged with MC (30 mg/kg, i. p. x 5 days) or PB (80 mg/kg, i. p. x 5 days) when young at age (approx. 7 weeks) compared to animals exposed to MC or PB alone. Further, challenge of the control and prenatally exposed offspring with a single sub-convulsant dose of lindane resulted in an earlier onset and increased incidence of convulsions in the offspring prenatally exposed to lindane have demonstrated sensitivity of the CYPs in the prenatally exposed offspring. Our data assume significance as the subtle changes in the expression profiles of hepatic and cerebral CYPs in rat offspring during postnatal development could modify the adult response to a later exposure to xenobiotics.

  5. Diagnostic cerebral angiography affects the tonus of the major cerebral arteries.

    PubMed

    Kochanowicz, Jan; Lewszuk, Andrzej; Kordecki, Kazimierz; Swiercz, Mirosław; Mariak, Zenon

    2007-05-01

    Vascular reactions after cerebral angiography have not been hitherto extensively explored due to the lack of a simple, easily available, and safe method for the measurement of cerebral circulation. We attempted to study cerebral circulation with color Doppler transcranial sonography (TCCS) in consecutive patients before and immediately after digital subtraction angiography (DSA). TCCS examination of the major cerebral arteries was carried out in 52 patients (25 females and 27 males), mean age 50.3+/-11.5 years, before and 10-20 minutes after cerebral angiography. A Toshiba Aplio SSA 770A system with a 2.5-MHz sector transducer was used. In general terms, there was a tendency after DSA towards a slight decrease in peak systolic blood velocity and an increase in mean and end-diastolic velocity in all the major cerebral arteries which, in turn, led to a decrease in the impedance index (pulsatility index, PI). In 19 patients, the impedance index as measured in the middle cerebral artery decreased after DSA, in 29 it did not change, while in 4 patients PI increased. Discriminant analysis showed that the factors predisposing individuals to these adverse reactions were a low score on the Glasgow Coma Scale, etiological diagnosis of intracerebral bleeding, and a high value of the impedance index prior to the procedure. Contrast cerebral angiography may affect the tonus of cerebral vessels. In the majority of patients it caused vasodilatation to varying degrees and in a small sub-group vasoconstriction.

  6. Cerebral stimulation for the affective component of neuropathic pain

    PubMed Central

    Machado, Andre G.; Baker, Kenneth B.; Plow, Ela; Malone, Donald A.

    2012-01-01

    Objective To review the current state of cerebral stimulation for neuropathic pain and to propose that cerebral stimulation should aim at the affective sphere of chronic pain rather than solely focusing on the primary sensory-discriminative sphere. Methods The past and current goals of cerebral stimulation are reviewed as well as its limitations. A novel deep brain stimulation approach is proposed to evaluate this conceptual shift fromsomatosensory to affective sphere of pain targeting Approach Thalamic and other central pain syndromes aretypically intractable to current treatment methods, including cerebral neuromodulation of somatosensory pathways, leading to long-term distress and disability. Our modern understanding of chronic pain pathophysiology is based largely on the neuromatrix theory, where cognitive, affective and sensory-discriminative spheres contribute equally to the overall pain experience. During the last decade, the safety and feasibility of chronic stimulation of neural pathways related to mood and affect has been explored with promising results. Here, we propose a novel approach to modulate the affective sphere of chronic pain by targeting similar networks in patients with treatment-refractory central pain. Our primary goal is not to produce (or measure) analgesia, but rather to modulate the affective burden of chronic. Discussion Cerebral neuromodulation for neuropathic pain has had limited efficacy thus far. Shifting our aim to neural networks related to the affective sphere of pain may allow us to reduce pain conditioning and pain-related disability. Our ultimate goal is to promote rehabilitation from chronic pain - social and occupational. PMID:23094938

  7. Cerebral stimulation for the affective component of neuropathic pain.

    PubMed

    Machado, Andre G; Baker, Kenneth B; Plow, Ela; Malone, Donald A

    2013-01-01

    To review the current state of cerebral stimulation for neuropathic pain and to propose that cerebral stimulation should aim also at the affective sphere of chronic pain rather than solely focusing on the primary sensory-discriminative sphere. The past and current goals of cerebral stimulation are reviewed as well as its limitations. A novel deep brain stimulation approach is proposed to evaluate this conceptual shift from somatosensory to affective sphere of pain targeting. Thalamic and other central pain syndromes are typically intractable to current treatment methods, including cerebral neuromodulation of somatosensory pathways, leading to long-term distress and disability. Our modern understanding of chronic pain pathophysiology is based largely on the neuromatrix theory, where cognitive, affective, and sensory-discriminative spheres contribute equally to the overall pain experience. During the last decade, the safety and feasibility of chronic stimulation of neural pathways related to mood and affect has been explored with promising results. Here, we propose a novel approach to modulate the affective sphere of chronic pain by targeting similar networks in patients with treatment-refractory central pain. Our primary goal is not to produce (or measure) analgesia, but rather to modulate the affective burden of chronic pain. Cerebral neuromodulation for neuropathic pain has had limited efficacy thus far. Shifting our aim to neural networks related to the affective sphere of pain may allow us to reduce pain conditioning and pain-related disability. Our ultimate goal is to promote rehabilitation from chronic pain-social and occupational. © 2012 International Neuromodulation Society.

  8. Coexistence of translocated cytochrome c and nitrated protein in neurons of the rat cerebral cortex after oxygen and glucose deprivation.

    PubMed

    Alonso, D; Encinas, J M; Uttenthal, L O; Boscá, L; Serrano, J; Fernández, A P; Castro-Blanco, S; Santacana, M; Bentura, M L; Richart, A; Fernández-Vizarra, P; Rodrigo, J

    2002-01-01

    Changes in the distribution of immunoreactive cytochrome c and protein nitration were studied in the rat cerebral cortex after oxygen and glucose deprivation by bright field, confocal and electron microscopy. In control cerebral cortex, nitrotyrosine immunoreactivity indicating protein nitration was found mostly in the neuronal nuclear region, with only a small amount distributed in the cytosol, whereas cytochrome c immunoreactivity was found at the inner membrane and in the intermembrane space of the mitochondria. During the recovery phase after oxygen and glucose deprivation, cytochrome c immunoreactivity was released from the intermembrane space of swollen mitochondria into the surrounding cytosol. The cytosol now also displayed nitrotyrosine immunoreactivity, which had diminished in the nuclear region. Both immunoreactivities were dispersed throughout the soma and processes of the cortical neurons. These changes were largely prevented by the administration of cyclosporin A, which inhibits both the mitochondrial permeability transition and the neuronal isoform of nitric oxide synthase while blocking the induction of the inducible isoform. Ischemia/reperfusion injury increases the production of nitric oxide, reactive oxygen species and intracellular factors that damage the mitochondria and liberate apoptotic factors. We suggest that translocation of cytochrome c from the mitochondria to the cytosol, which has been shown to precede the mitochondrial permeability transition, could result from peroxynitrite-mediated nitration. This phenomenon is attenuated by cyclosporin A administration, suggesting a neuroprotective role for this agent.

  9. Cerebral vasospasm affects arterial critical closing pressure

    PubMed Central

    Varsos, Georgios V; Budohoski, Karol P; Czosnyka, Marek; Kolias, Angelos G; Nasr, Nathalie; Donnelly, Joseph; Liu, Xiuyun; Kim, Dong-Joo; Hutchinson, Peter J; Kirkpatrick, Peter J; Varsos, Vassilis G; Smielewski, Peter

    2015-01-01

    The effect of cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (SAH) on critical closing pressure (CrCP) has not been fully delineated. Using cerebral impedance methodology, we sought to assess the behavior of CrCP during CVS. As CrCP expresses the sum of intracranial pressure (ICP) and vascular wall tension, we also explored its role in reflecting changes in vascular tone occurring in small vessels distal to spasm. This retrospective analysis was performed using recordings from 52 patients, diagnosed with CVS through transcranial Doppler measurements. Critical closing pressure was calculated noninvasively using arterial blood pressure and blood flow velocity. Outcome was assessed at both discharge and 3 months after ictus with the Glasgow Outcome Scale. The onset of CVS caused significant decreases in CrCP (P=0.025), without any observed significant changes in ICP (P=0.134). Vasospasm induced asymmetry, with CrCP ipsilateral to CVS becoming significantly lower than contralateral (P=0.025). Unfavorable outcomes were associated with a significantly lower CrCP after the onset of CVS (discharge: P=0.014; 3 months after SAH: P=0.020). Critical closing pressure is reduced in the presence of CVS in both temporal and spatial assessments. As ICP remained unchanged during CVS, reduced CrCP most probably reflects a lower wall tension in dilated small vessels distal to spasm. PMID:25465041

  10. Labetalol decreases cerebral perfusion pressure without negatively affecting cerebral blood flow in hypertensive gravidas.

    PubMed

    Belfort, Michael A; Tooke-Miller, Cathy; Allen, John C; Dizon-Townson, Donna; Varner, Michael A

    2002-01-01

    To research the cerebral hemodynamic effects of labetalol in pregnant women with hypertension. Prospective observational study. Tertiary Care Medical Center. Pregnant patients with hypertension. Transcranial Doppler (TCD) ultrasound was used to measure the blood velocity in the middle cerebral arteries (MCA) of eight pregnant patients with hypertension, before and after the administration of a 200 mg oral dose of labetalol. Five patients had severe preeclampsia, and three had chronic hypertension with superimposed preeclampsia. MCA blood velocity and systemic blood pressure were measured simultaneously at the baseline, and at 60 and 180 min after labetalol. Selected cerebral hemodynamic parameters were compared with normative curves. Values outside of the 5th and 95th percentiles were regarded as abnormal. Cerebral perfusion pressure (CPP), resistance area product (RAP), and cerebral flow index (CFI). Patient age, gestational age, and parity were similar to those of the normal women from whom the normative data were obtained. Women with hypertension had higher baseline CPP, MAP, and RAP than normal pregnant women, but their CFI was within the normal range. Labetalol reduced the CPP, as well as the systolic, diastolic, and mean BP significantly at 60 and 180 min without significantly affecting the heart rate, MCA velocities, RAP, or CFI. Labetalol effectively reduces CPP, without affecting cerebral perfusion, primarily by a decrease in systemic blood pressure. This makes it an ideal agent for blood pressure control in severely hypertensive pregnant women.

  11. Tetrahydrocurcumin ameliorates homocysteinylated cytochrome-c mediated autophagy in hyperhomocysteinemia mice after cerebral ischemia.

    PubMed

    Tyagi, Neetu; Qipshidze, Natia; Munjal, Charu; Vacek, Jonathan C; Metreveli, Naira; Givvimani, Srikanth; Tyagi, Suresh C

    2012-05-01

    High levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy), contribute to autophagy and ischemia/reperfusion injury (I/R). Previous studies have shown that I/R injury and HHcy cause increased cerebrovascular permeability; however, the associated mechanism remains obscure. Interestingly, during HHcy, cytochome-c becomes homocysteinylated (Hcy-cyto-c). Cytochrome-c (cyto-c) transports electrons and facilitates bioenergetics in the system. However, its role in autophagy during ischemia/reperfusion injury is unclear. Tetrahydrocurcumin (THC) is a major herbal antioxidant and anti-inflammatory agent. Therefore, the objective of this study was to determine whether THC ameliorates autophagy during ischemia/reperfusion injury by reducing homocysteinylation of cyto-c in hyperhomocysteinemia pathological condition. To test this hypothesis, we employed 8-10-week-old male cystathionine-beta-synthase heterozygote knockout (CBS⁺/⁻) mice (genetically hyperhomocystemic mice). Experimental group was: CBS⁺/⁻, CBS⁺/⁻ + THC (25 mg/kg in 0.1% DMSO dose); CBS ⁺/⁻/I/R, and CBS⁺/⁻/I/R + THC (25 mg/kg in 0.1% DMSO dose). Ischemia was performed for 30 min and reperfusion for 72 h. THC was injected intra-peritoneally (I.P.) once daily for a period of 3 days after 30 min of ischemia. The infarct area was measured using 2,3,5-triphenyltetrazolium chloride staining. Permeability was determined by brain edema and Evans Blue extravasation. The brain tissues were analyzed for oxidative stress, matrix metalloproteinase-9 (MMP-9), damage-regulated autophagy modulator (DRAM), and microtubule-associated protein 1 light chain 3 (LC3) by Western blot. The mRNA levels of S-adenosyl-L-homocysteine hydrolases (SAHH) and methylenetetrahydrofolate reductase (MTHFR) genes were measured by quantitative real-time polymerase chain reaction. Co-immunoprecipitation was used to determine the homocysteinylation of cyto-c. We found that brain edema and Evans Blue leakage were

  12. Interrelationship Between Broadband NIRS Measurements of Cerebral Cytochrome C Oxidase and Systemic Changes Indicates Injury Severity in Neonatal Encephalopathy.

    PubMed

    Bale, Gemma; Mitra, Subhabrata; de Roever, Isabel; Chan, Marcus; Caicedo-Dorado, Alexander; Meek, Judith; Robertson, Nicola; Tachtsidis, Ilias

    2016-01-01

    Perinatal hypoxic ischaemic encephalopathy (HIE) is associated with severe neurodevelopmental problems and mortality. There is a clinical need for techniques to provide cotside assessment of the injury extent. This study aims to use non-invasive cerebral broadband near-infrared spectroscopy (NIRS) in combination with systemic physiology to assess the severity of HIE injury. Broadband NIRS is used to measure the changes in haemodynamics, oxygenation and the oxidation state of cytochrome c oxidase (oxCCO). We used canonical correlation analysis (CCA), a multivariate statistical technique, to measure the relationship between cerebral broadband NIRS measurements and systemic physiology. A strong relationship between the metabolic marker, oxCCO, and systemic changes indicated severe brain injury; if more than 60 % of the oxCCO signal could be explained by the systemic variations, then the neurodevelopmental outcome was poor. This boundary has high sensitivity and specificity (100 and 83 %, respectively). Broadband NIRS measured concentration changes of the oxidation state of cytochrome c oxidase has the potential to become a useful cotside tool for assessment of injury severity following hypoxic ischaemic brain injury.

  13. Factors affecting the cerebral network in brain tumor patients.

    PubMed

    Heimans, Jan J; Reijneveld, Jaap C

    2012-06-01

    Brain functions, including cognitive functions, are frequently disturbed in brain tumor patients. These disturbances may result from the tumor itself, but also from the treatment directed against the tumor. Surgery, radiotherapy and chemotherapy all may affect cerebral functioning, both in a positive as well as in a negative way. Apart from the anti-tumor treatment, glioma patients often receive glucocorticoids and anti-epileptic drugs, which both also have influence on brain functioning. The effect of a brain tumor on cerebral functioning is often more global than should be expected on the basis of the local character of the disease, and this is thought to be a consequence of disturbance of the cerebral network as a whole. Any network, whether it be a neural, a social or an electronic network, can be described in parameters assessing the topological characteristics of that particular network. Repeated assessment of neural network characteristics in brain tumor patients during their disease course enables study of the dynamics of neural networks and provides more insight into the plasticity of the diseased brain. Functional MRI, electroencephalography and especially magnetoencephalography are used to measure brain function and the signals that are being registered with these techniques can be analyzed with respect to network characteristics such as "synchronization" and "clustering". Evidence accumulates that loss of optimal neural network architecture negatively impacts complex cerebral functioning and also decreases the threshold to develop epileptic seizures. Future research should be focused on both plasticity of neural networks and the factors that have impact on that plasticity as well as the possible role of assessment of neural network characteristics in the determination of cerebral function during the disease course.

  14. Imprinting of cerebral cytochrome P450s in offsprings prenatally exposed to cypermethrin augments toxicity on rechallenge

    NASA Astrophysics Data System (ADS)

    Singh, Anshuman; Agrahari, Anita; Singh, Radhadutt; Yadav, Sanjay; Srivastava, Vikas; Parmar, Devendra

    2016-11-01

    Epigenetic studies were carried in the rat offsprings, born to dams treated with cypermethrin (orally; 5.0 mg/kg) from gestation day (GD) 5 to 21 and rechallenged with cypermethrin (orally; 10 mg/kg for 6 days), at adulthood (12 weeks) to understand the mechanism underlying the overexpression of cerebral cytochrome P450s (CYPs) in exposed offsprings. The data revealed alterations in histone H3 acetylation and DNA methylation in promoter regions of CYP1A- and 2B- isoenzymes in the brain isolated from rechallenged animals. Further, bisulphite sequencing revealed critical CpG methylation changes in BARBIE BOX (Barbiturate response element) and BTE (Basal transcription element) in promoter of CYP2B1 in the brain isolated from rechallenged animals. Western blotting and DNA laddering/fragmentation studies revealed a greater magnitude of increase in the signalling pathways associated with apoptosis in the rechallenged animals. The data have indicated that overexpression of cerebral CYPs could be due to the imprinting of CYPs. Further, increased apoptosis observed in the rechallenged offsprings has suggested that these epigenetic changes in CYPs may predispose the prenatally exposed offsprings to the neurotoxic effects of other centrally acting drugs and chemicals when subsequently rechallenged later at life.

  15. Imprinting of cerebral cytochrome P450s in offsprings prenatally exposed to cypermethrin augments toxicity on rechallenge

    PubMed Central

    Singh, Anshuman; Agrahari, Anita; Singh, RadhaDutt; Yadav, Sanjay; Srivastava, Vikas; Parmar, Devendra

    2016-01-01

    Epigenetic studies were carried in the rat offsprings, born to dams treated with cypermethrin (orally; 5.0 mg/kg) from gestation day (GD) 5 to 21 and rechallenged with cypermethrin (orally; 10 mg/kg for 6 days), at adulthood (12 weeks) to understand the mechanism underlying the overexpression of cerebral cytochrome P450s (CYPs) in exposed offsprings. The data revealed alterations in histone H3 acetylation and DNA methylation in promoter regions of CYP1A- and 2B- isoenzymes in the brain isolated from rechallenged animals. Further, bisulphite sequencing revealed critical CpG methylation changes in BARBIE BOX (Barbiturate response element) and BTE (Basal transcription element) in promoter of CYP2B1 in the brain isolated from rechallenged animals. Western blotting and DNA laddering/fragmentation studies revealed a greater magnitude of increase in the signalling pathways associated with apoptosis in the rechallenged animals. The data have indicated that overexpression of cerebral CYPs could be due to the imprinting of CYPs. Further, increased apoptosis observed in the rechallenged offsprings has suggested that these epigenetic changes in CYPs may predispose the prenatally exposed offsprings to the neurotoxic effects of other centrally acting drugs and chemicals when subsequently rechallenged later at life. PMID:27853314

  16. Inherited neurovascular diseases affecting cerebral blood vessels and smooth muscle.

    PubMed

    Sam, Christine; Li, Fei-Feng; Liu, Shu-Lin

    2015-10-01

    Neurovascular diseases are among the leading causes of mortality and permanent disability due to stroke, aneurysm, and other cardiovascular complications. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Marfan syndrome are two neurovascular disorders that affect smooth muscle cells through accumulation of granule and osmiophilic materials and defective elastic fiber formations respectively. Moyamoya disease, hereditary hemorrhagic telangiectasia (HHT), microcephalic osteodysplastic primordial dwarfism type II (MOPD II), and Fabry's disease are disorders that affect the endothelium cells of blood vessels through occlusion or abnormal development. While much research has been done on mapping out mutations in these diseases, the exact mechanisms are still largely unknown. This paper briefly introduces the pathogenesis, genetics, clinical symptoms, and current methods of treatment of the diseases in the hope that it can help us better understand the mechanism of these diseases and work on ways to develop better diagnosis and treatment.

  17. Cycle affects imidacloprid efficiency by mediating cytochrome P450 expression in the brown planthopper Nilaparvata lugens.

    PubMed

    Kang, K; Yang, P; Pang, R; Yue, L; Zhang, W

    2017-10-01

    Circadian clocks influence most behaviours and physiological activities in animals, including daily fluctuations in metabolism. However, how the clock gene cycle influences insects' responses to pesticides has rarely been reported. Here, we provide evidence that cycle affects imidacloprid efficacy by mediating the expression of cytochrome P450 genes in the brown planthopper (BPH) Nilaparvata lugens, a serious insect pest of rice. Survival bioassays showed that the susceptibility of BPH adults to imidacloprid differed significantly between the two time points tested [Zeitgeber Time 8 (ZT8) and ZT4]. After cloning the cycle gene in the BPH (Nlcycle), we found that Nlcycle was expressed at higher levels in the fat body and midgut, and its expression was rhythmic with two peaks. Knockdown of Nlcycle affected the expression levels and rhythms of cytochrome P450 genes as well as susceptibility to imidacloprid. The survival rates of BPH adults after treatment with imidacloprid did not significantly differ between ZT4 and ZT8 after double-stranded Nlcycle treatment. These findings can be used to improve pesticide use and increase pesticide efficiency in the field. © 2017 The Royal Entomological Society.

  18. Image reconstruction of oxidized cerebral cytochrome C oxidase changes from broadband near-infrared spectroscopy data.

    PubMed

    Brigadoi, Sabrina; Phan, Phong; Highton, David; Powell, Samuel; Cooper, Robert J; Hebden, Jeremy; Smith, Martin; Tachtsidis, Ilias; Elwell, Clare E; Gibson, Adam P

    2017-04-01

    In diffuse optical tomography (DOT), overlapping and multidistance measurements are required to reconstruct depth-resolved images of oxy- ([Formula: see text]) and deoxy- (HHb) hemoglobin concentration changes occurring in the brain. These can be considered an indirect measure of brain activity, under the assumption of intact neurovascular coupling. Broadband systems also allow changes in the redox state of cytochrome c oxidase (oxCCO) to be measured, which can be an important biomarker when neurovascular coupling is impaired. We used DOT to reconstruct images of [Formula: see text], [Formula: see text], and [Formula: see text] from data acquired with a broadband system. Four healthy volunteers were measured while performing a visual stimulation task (4-Hz inverting checkerboard). The broadband system was configured to allow multidistance and overlapping measurements of the participants' visual cortex with 32 channels. A multispectral approach was employed to reconstruct changes in concentration of the three chromophores during the visual stimulation. A clear and focused activation was reconstructed in the left occipital cortex of all participants. The difference between the residuals of the three-chromophore model and of the two-chromophore model (recovering only [Formula: see text] and [Formula: see text]) exhibits a spectrum similar to that of oxCCO. These results form a basis for further studies aimed to further optimize image reconstruction of [Formula: see text].

  19. Cytochrome c oxidase response to changes in cerebral oxygen delivery in the adult brain shows higher brain-specificity than haemoglobin☆

    PubMed Central

    Kolyva, Christina; Ghosh, Arnab; Tachtsidis, Ilias; Highton, David; Cooper, Chris E.; Smith, Martin; Elwell, Clare E.

    2014-01-01

    The redox state of cerebral mitochondrial cytochrome c oxidase monitored with near-infrared spectroscopy (Δ[oxCCO]) is a signal with strong potential as a non-invasive, bedside biomarker of cerebral metabolic status. We hypothesised that the higher mitochondrial density of brain compared to skin and skull would lead to evidence of brain-specificity of the Δ[oxCCO] signal when measured with a multi-distance near-infrared spectroscopy (NIRS) system. Measurements of Δ[oxCCO] as well as of concentration changes in oxygenated (Δ[HbO2]) and deoxygenated haemoglobin (Δ[HHb]) were taken at multiple source-detector distances during systemic hypoxia and hypocapnia (decrease in cerebral oxygen delivery), and hyperoxia and hypercapnia (increase in cerebral oxygen delivery) from 15 adult healthy volunteers. Increasing source-detector spacing is associated with increasing light penetration depth and thus higher sensitivity to cerebral changes. An increase in Δ[oxCCO] was observed during the challenges that increased cerebral oxygen delivery and the opposite was observed when cerebral oxygen delivery decreased. A consistent pattern of statistically significant increasing amplitude of the Δ[oxCCO] response with increasing light penetration depth was observed in all four challenges, a behaviour that was distinctly different from that of the haemoglobin chromophores, which did not show this statistically significant depth gradient. This depth-dependence of the Δ[oxCCO] signal corroborates the notion of higher concentrations of CCO being present in cerebral tissue compared to extracranial components and highlights the value of NIRS-derived Δ[oxCCO] as a brain-specific signal of cerebral metabolism, superior in this aspect to haemoglobin. PMID:23707584

  20. Cytochrome c oxidase response to changes in cerebral oxygen delivery in the adult brain shows higher brain-specificity than haemoglobin.

    PubMed

    Kolyva, Christina; Ghosh, Arnab; Tachtsidis, Ilias; Highton, David; Cooper, Chris E; Smith, Martin; Elwell, Clare E

    2014-01-15

    The redox state of cerebral mitochondrial cytochrome c oxidase monitored with near-infrared spectroscopy (Δ[oxCCO]) is a signal with strong potential as a non-invasive, bedside biomarker of cerebral metabolic status. We hypothesised that the higher mitochondrial density of brain compared to skin and skull would lead to evidence of brain-specificity of the Δ[oxCCO] signal when measured with a multi-distance near-infrared spectroscopy (NIRS) system. Measurements of Δ[oxCCO] as well as of concentration changes in oxygenated (Δ[HbO2]) and deoxygenated haemoglobin (Δ[HHb]) were taken at multiple source-detector distances during systemic hypoxia and hypocapnia (decrease in cerebral oxygen delivery), and hyperoxia and hypercapnia (increase in cerebral oxygen delivery) from 15 adult healthy volunteers. Increasing source-detector spacing is associated with increasing light penetration depth and thus higher sensitivity to cerebral changes. An increase in Δ[oxCCO] was observed during the challenges that increased cerebral oxygen delivery and the opposite was observed when cerebral oxygen delivery decreased. A consistent pattern of statistically significant increasing amplitude of the Δ[oxCCO] response with increasing light penetration depth was observed in all four challenges, a behaviour that was distinctly different from that of the haemoglobin chromophores, which did not show this statistically significant depth gradient. This depth-dependence of the Δ[oxCCO] signal corroborates the notion of higher concentrations of CCO being present in cerebral tissue compared to extracranial components and highlights the value of NIRS-derived Δ[oxCCO] as a brain-specific signal of cerebral metabolism, superior in this aspect to haemoglobin.

  1. Cytochrome P450 and matrix metalloproteinase genetic modifiers of disease severity in Cerebral Cavernous Malformation type 1

    PubMed Central

    Choquet, Hélène; Trapani, Eliana; Goitre, Luca; Trabalzini, Lorenza; Akers, Amy; Fontanella, Marco; Hart, Blaine L.; Morrison, Leslie A.; Pawlikowska, Ludmila; Kim, Helen; Retta, Saverio Francesco

    2016-01-01

    Background Familial Cerebral Cavernous Malformation type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and characterized by multiple brain lesions. CCM lesions manifest across a range of different phenotypes, including wide differences in lesion number, size and susceptibility to intracerebral hemorrhage (ICH). Oxidative stress plays an important role in cerebrovascular disease pathogenesis, raising the possibility that inter-individual variability in genes related to oxidative stress may contribute to the phenotypic differences observed in CCM1 disease. Here, we investigated whether candidate oxidative stress-related cytochrome P450 (CYP) and matrix metalloproteinase (MMP) genetic markers grouped by superfamilies, families or genes, or analyzed individually influence the severity of CCM1 disease. Methods Clinical assessment and cerebral susceptibility-weighted magnetic resonance imaging (SWI) were performed to determine total and large (≥5 mm in diameter) lesion counts as well as ICH in 188 Hispanic CCM1 patients harboring the founder KRIT1/CCM1 ‘common Hispanic mutation’ (CCM1–CHM). Samples were genotyped on the Affymetrix Axiom Genome-Wide LAT1 Human Array. We analyzed 1,122 genetic markers (both single nucleotide polymorphisms (SNPs) and insertion/deletions) grouped by CYP and MMP superfamily, family or gene for association with total or large lesion count and ICH adjusted for age at enrollment and gender. Genetic markers bearing the associations were then analyzed individually. Results The CYP superfamily showed a trend toward association with total lesion count (P=0.057) and large lesion count (P=0.088) in contrast to the MMP superfamily. The CYP4 and CYP8 families were associated with either large lesion count or total lesion count (P=0.014), and two other families (CYP46 and the MMP Stromelysins) were associated with ICH (P=0.011 and 0.007, respectively). CYP4F12 rs11085971, CYP8A

  2. Dynamic touch is affected in children with cerebral palsy.

    PubMed

    Ocarino, Juliana M; Fonseca, Sergio T; Silva, Paula L P; Gonçalves, Gabriela G P; Souza, Thales R; Mancini, Marisa C

    2014-02-01

    Children with developmental disorders such as cerebral palsy have limited opportunities for effortful interactions with objects and tools. The goal of the study was to investigate whether children with cerebral palsy have deficits in their ability to perceive object length by dynamic touch when compared to typically developing children. Fourteen children with typical development and 12 children with cerebral palsy were asked to report the length of hand-held rods after wielding them out of sight. Multilevel regression models indicated that I1 (maximum principal moment of inertia) was a significant predictor of perceived length - LP (p<.0001). The effect of I1 on LP was significantly different among children (p=.001) and the presence of cerebral palsy (group factor) partially explained such variance (p=.002). In addition, accuracy and reliability of the length judgments made by children with cerebral palsy were significantly lower than the typically developing children (p<.05). Theoretical and clinical implications of these results were identified and discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Overexpression of cerebral and hepatic cytochrome P450s alters behavioral activity of rat offspring following prenatal exposure to lindane

    SciTech Connect

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

    2007-12-15

    Oral administration of different doses (0.0625, 0.125 or 0.25 mg/kg corresponding to 1/1400th, 1/700th or 1/350th of LD{sub 50}) of lindane to the pregnant Wistar rats from gestation days 5 to 21 were found to produce a dose-dependent increase in the activity of cytochrome P450 (CYP)-dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMA-d) in brain and liver of offspring postnatally at 3 weeks. The increase in the activity of CYP monooxygenases was found to be associated with the increase in the mRNA and protein expression of xenobiotic metabolizing CYP1A, 2B and 2E1 isoenzymes in the brain and liver of offspring. Dose-dependent alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 3 weeks have suggested that increase in CYP activity may possibly lead to the formation of metabolites to the levels that may be sufficient to alter the behavioral activity of the offspring. Interestingly, the inductive effect on cerebral and hepatic CYPs was found to persist postnatally up to 6 weeks in the offspring at the relatively higher doses (0.125 and 0.25 mg/kg) of lindane and up to 9 weeks at the highest dose (0.25 mg/kg), though the magnitude of induction was less than that observed at 3 weeks. Alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 6 and 9 weeks, though significant only in the offspring at 3 and 6-week of age, have further indicated that due to the reduced activity of the CYPs during the ontogeny, lindane and its metabolites may not be effectively cleared from the brain. The data suggest that low dose prenatal exposure to the pesticide has the potential to produce overexpression of xenobiotic metabolizing CYPs in brain and liver of the offspring which may account for the behavioral changes observed in the offspring.

  4. Sevoflurane affects evoked electromyography monitoring in cerebral palsy

    PubMed Central

    Chen, Xin; Xu, Lufeng; Wang, Yuanlin; Xu, Feng; Du, Yemu

    2016-01-01

    Abstract Background To explore the effect of sevoflurane inhalation anesthesia on evoked electromyography monitoring of spinal nerve root in children associated with cerebral palsy. Methodology Children with cerebral palsy (n=40) were selected and further divided into 1MAC (minimum alveolar concentration) sevoflurane group and 2MAC sevoflurane group. Following the induction of anesthesia, Nicolet Endeavor-CR16 channel electrophysiological monitor was used to implement three times of successive electrical stimulation with interval of 5 sec at 3.50 mA. Results Our results suggested a statistical significance of amplitude retention ratio and latency in the sevoflurane inhalation time (P<0.01), with an interaction effect between the sevoflurane inhalation time and concentration for amplitude retention ratio (P<0.01), while there is no interaction effect between the sevoflurane inhalation time and concentration for latency (P>0.05). Compared to 1MAC sevoflurane group, the amplitude retention ratio of 2MAC sevoflurane group decreased remarkably (P<0.01) and the latency of 2MAC sevoflurane group extended at T3 and T4 (P<0.05 or P<0.01). Conclusions In evoked electromyography monitoring of spinal nerve root in children with cerebral palsy, with the increasing of concentration and duration of sevoflurane inhalation, evoked electromyogram retention ratio reduces gradually, latency extends and the retention ratio has more changes than the latency. PMID:28352782

  5. Mapping patterns of depression-related brain regions with cytochrome oxidase histochemistry: relevance of animal affective systems to human disorders, with a focus on resilience to adverse events.

    PubMed

    Harro, Jaanus; Kanarik, Margus; Matrov, Denis; Panksepp, Jaak

    2011-10-01

    The search for novel antidepressants may be facilitated by pre-clinical animal models that relay on specific neural circuit and related neurochemical endpoint measures, which are anchored in concrete neuro-anatomical and functional neural-network analyzes. One of the most important initial considerations must be which regions of the brain are candidates for the maladaptive response to depressogenic challenges. Consideration of persistent differences or changes in the activity of cerebral networks can be achieved by mapping oxidative metabolism in ethologically or pathogenetically relevant animal models. Cytochrome oxidase histochemistry is a technique suitable to detect regional long-term brain activity changes relative to control conditions and has been used in a variety of animal models. This work is summarized and indicates that major changes occur mainly in subcortical areas, highlighting specific brain regions where some alterations in regional oxidative metabolism may represent adaptive changes to depressogenic adverse life events, while others may reflect failures of adaptation. Many of these changes in oxidative metabolism may depend upon the integrity of serotonergic neurotransmission, and occur in several brain regions shown by other techniques to be involved in endogenous affective circuits that control emotional behaviors as well as related higher brain regions that integrate learning and cognitive information processing. These brain regions appear as primary targets for further identification of endophenotypes specific to affective disorders.

  6. Argon does not affect cerebral circulation or metabolism in male humans.

    PubMed

    Grüne, Frank; Kazmaier, Stephan; Hoeks, Sanne Elisabeth; Stolker, Robert Jan; Coburn, Marc; Weyland, Andreas

    2017-01-01

    Accumulating data have recently underlined argon´s neuroprotective potential. However, to the best of our knowledge, no data are available on the cerebrovascular effects of argon (Ar) in humans. We hypothesized that argon inhalation does not affect mean blood flow velocity of the middle cerebral artery (Vmca), cerebral flow index (FI), zero flow pressure (ZFP), effective cerebral perfusion pressure (CPPe), resistance area product (RAP) and the arterio-jugular venous content differences of oxygen (AJVDO2), glucose (AJVDG), and lactate (AJVDL) in anesthetized patients. In a secondary analysis of an earlier controlled cross-over trial we compared parameters of the cerebral circulation under 15 minutes exposure to 70%Ar/30%O2 versus 70%N2/30%O2 in 29 male patients under fentanyl-midazolam anaesthesia before coronary surgery. Vmca was measured by transcranial Doppler sonography. ZFP and RAP were estimated by linear regression analysis of pressure-flow velocity relationships of the middle cerebral artery. CPPe was calculated as the difference between mean arterial pressure and ZFP. AJVDO2, AJVDG and AJVDL were calculated as the differences in contents between arterial and jugular-venous blood of oxygen, glucose, and lactate. Statistical analysis was done by t-tests and ANOVA. Mechanical ventilation with 70% Ar did not cause any significant changes in mean arterial pressure, Vmca, FI, ZFP, CPPe, RAP, AJVDO2, AJVDG, and AJVDL. Short-term inhalation of 70% Ar does not affect global cerebral circulation or metabolism in male humans under general anaesthesia.

  7. From Jöbsis to the present day: a review of clinical near-infrared spectroscopy measurements of cerebral cytochrome-c-oxidase

    NASA Astrophysics Data System (ADS)

    Bale, Gemma; Elwell, Clare E.; Tachtsidis, Ilias

    2016-09-01

    Near-infrared spectroscopy (NIRS) measurements of cytochrome-c-oxidase (CCO) have the potential to yield crucial information about cerebral metabolism at the patient bedside. Developments in instrumentation and the analytical methods used to resolve changes in CCO have led to many clinical applications of the measurement since its first demonstration in 1977 by Jöbsis. There is a substantial literature of work on measures of CCO in animal and in vitro studies; however, this review focuses on translational studies. Almost 40 years from the advent of the first measurement of CCO using NIRS, this signal continues to hold significant interest in our understanding of the human brain in health and disease. We discuss methodologies for obtaining NIRS measurements of CCO in the clinic and review studies in neonates and adults.

  8. From Jöbsis to the present day: a review of clinical near-infrared spectroscopy measurements of cerebral cytochrome-c-oxidase.

    PubMed

    Bale, Gemma; Elwell, Clare E; Tachtsidis, Ilias

    2016-09-01

    Near-infrared spectroscopy (NIRS) measurements of cytochrome-c-oxidase (CCO) have the potential to yield crucial information about cerebral metabolism at the patient bedside. Developments in instrumentation and the analytical methods used to resolve changes in CCO have led to many clinical applications of the measurement since its first demonstration in 1977 by Jöbsis. There is a substantial literature of work on measures of CCO in animal and in vitro studies; however, this review focuses on translational studies. Almost 40 years from the advent of the first measurement of CCO using NIRS, this signal continues to hold significant interest in our understanding of the human brain in health and disease. We discuss methodologies for obtaining NIRS measurements of CCO in the clinic and review studies in neonates and adults.

  9. HIV and chronic methamphetamine dependence affect cerebral blood flow.

    PubMed

    Ances, Beau M; Vaida, Florin; Cherner, Mariana; Yeh, Melinda J; Liang, Christine L; Gardner, Carly; Grant, Igor; Ellis, Ronald J; Buxton, Richard B

    2011-09-01

    Human immunodeficiency virus (HIV) and methamphetamine (METH) dependence are independently associated with neuronal dysfunction. The coupling between cerebral blood flow (CBF) and neuronal activity is the basis of many task-based functional neuroimaging techniques. We examined the interaction between HIV infection and a previous history of METH dependence on CBF within the lenticular nuclei (LN). Twenty-four HIV-/METH-, eight HIV-/METH+, 24 HIV+/METH-, and 15 HIV+/METH+ participants performed a finger tapping paradigm. A multiple regression analysis of covariance assessed associations and two-way interactions between CBF and HIV serostatus and/or previous history of METH dependence. HIV+ individuals had a trend towards a lower baseline CBF (-10%, p = 0.07) and greater CBF changes for the functional task (+32%, p = 0.01) than HIV- subjects. Individuals with a previous history of METH dependence had a lower baseline CBF (-16%, p = 0.007) and greater CBF changes for a functional task (+33%, p = 0.02). However, no interaction existed between HIV serostatus and previous history of METH dependence for either baseline CBF (p = 0.53) or CBF changes for a functional task (p = 0.10). In addition, CBF and volume in the LN were not correlated. A possible additive relationship could exist between HIV infection and a history of METH dependence on CBF with a previous history of METH dependence having a larger contribution. Abnormalities in CBF could serve as a surrogate measure for assessing the chronic effects of HIV and previous METH dependence on brain function.

  10. Effectiveness of Adaptive Pretend Play on Affective Expression and Imagination of Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Hsieh, Hsieh-Chun

    2012-01-01

    Purpose: Children with cerebral palsy (CP) have difficulty participating in role-pretending activities. The concept of adaptive play makes play accessible by modifying play materials for different needs or treatment goals for children with CP. This study examines the affective expressions and imagination in children with CP as a function of…

  11. Does Intellectual Disability Affect the Development of Dental Caries in Patients with Cerebral Palsy?

    ERIC Educational Resources Information Center

    Moreira, Rafaela Nogueira; Alcantara, Carlos Eduardo Pinto; Mota-Veloso, Isabella; Marinho, Sandra Aparecida; Ramos-Jorge, Maria L.; Oliveira-Ferreira, Fernanda

    2012-01-01

    The aim of this study was to evaluate if the severity of intellectual disability is a factor that affects the development of dental cavities in patients with cerebral palsy. This cross-sectional study was conducted on 165 individuals who were selected from a physical rehabilitation center, a special public school and a regular public school. Of…

  12. Effectiveness of Adaptive Pretend Play on Affective Expression and Imagination of Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Hsieh, Hsieh-Chun

    2012-01-01

    Purpose: Children with cerebral palsy (CP) have difficulty participating in role-pretending activities. The concept of adaptive play makes play accessible by modifying play materials for different needs or treatment goals for children with CP. This study examines the affective expressions and imagination in children with CP as a function of…

  13. Does Intellectual Disability Affect the Development of Dental Caries in Patients with Cerebral Palsy?

    ERIC Educational Resources Information Center

    Moreira, Rafaela Nogueira; Alcantara, Carlos Eduardo Pinto; Mota-Veloso, Isabella; Marinho, Sandra Aparecida; Ramos-Jorge, Maria L.; Oliveira-Ferreira, Fernanda

    2012-01-01

    The aim of this study was to evaluate if the severity of intellectual disability is a factor that affects the development of dental cavities in patients with cerebral palsy. This cross-sectional study was conducted on 165 individuals who were selected from a physical rehabilitation center, a special public school and a regular public school. Of…

  14. Up-regulation of cerebral cytochrome-c-oxidase and hemodynamics by transcranial infrared laser stimulation: A broadband near-infrared spectroscopy study.

    PubMed

    Wang, Xinlong; Tian, Fenghua; Reddy, Divya D; Nalawade, Sahil S; Barrett, Douglas W; Gonzalez-Lima, Francisco; Liu, Hanli

    2017-01-01

    Transcranial infrared laser stimulation (TILS) is a noninvasive form of brain photobiomulation. Cytochrome-c-oxidase (CCO), the terminal enzyme in the mitochondrial electron transport chain, is hypothesized to be the primary intracellular photoacceptor. We hypothesized that TILS up-regulates cerebral CCO and causes hemodynamic changes. We delivered 1064-nm laser stimulation to the forehead of healthy participants ( n = 11), while broadband near-infrared spectroscopy was utilized to acquire light reflectance from the TILS-treated cortical region before, during, and after TILS. Placebo experiments were also performed for accurate comparison. Time course of spectroscopic readings were analyzed and fitted to the modified Beer-Lambert law. With respect to the placebo readings, we observed (1) significant increases in cerebral concentrations of oxidized CCO (Δ[CCO]; >0.08 µM; p < 0.01), oxygenated hemoglobin (Δ[HbO]; >0.8 µM; p < 0.01), and total hemoglobin (Δ[HbT]; >0.5 µM; p < 0.01) during and after TILS, and (2) linear interplays between Δ[CCO] versus Δ[HbO] and between Δ[CCO] versus Δ[HbT]. Ratios of Δ[CCO]/Δ[HbO] and Δ[CCO]/Δ[HbT] were introduced as TILS-induced metabolic-hemodynamic coupling indices to quantify the coupling strength between TILS-enhanced cerebral metabolism and blood oxygen supply. This study provides the first demonstration that TILS causes up-regulation of oxidized CCO in the human brain, and contributes important insight into the physiological mechanisms.

  15. Dopamine therapy does not affect cerebral autoregulation during hypotension in newborn piglets

    PubMed Central

    Hahn, Gitte Holst; Greisen, Gorm

    2017-01-01

    Background Hypotensive neonates who have been treated with dopamine have poorer neurodevelopmental outcome than those who have not been treated with dopamine. We speculate that dopamine stimulates adrenoceptors on cerebral arteries causing cerebral vasoconstriction. This vasoconstriction might lead to a rightward shift of the cerebral autoregulatory curve; consequently, infants treated with dopamine would have a higher risk of low cerebral blood flow at a blood pressure that is otherwise considered “safe”. Methods In anaesthetized piglets, perfusion of the brain, monitored with laser-doppler flowmetry, and cerebral venous saturation was measured at different levels of hypotension. Each piglet was studied in two phases: a phase with stepwise decreases in MAP and a phase with stepwise increases in MAP. We randomized the order of the two phases, whether dopamine was given in the first or second phase, and the infusion rate of dopamine (10, 25, or 40 μg/kg/min). In/deflation of a balloon catheter, placed in vena cava, induced different levels of hypotension. At each level of hypotension, fluctuations in MAP were induced by in/deflations of a balloon catheter in descending aorta. Results During measurements, PaCO2 and arterial saturation were stable. MAP levels ranged between 14 and 82 mmHg. Cerebral autoregulation (CA) capacity was calculated as the ratio between %-change in cerebrovascular resistance and %-change in MAP induced by the in/deflation of the arterial balloon. A breakpoint in CA capacity was identified at a MAP of 38±18 mmHg without dopamine and at 44±18, 31±14, and 24±14 mmHg with dopamine infusion rates of 10, 25, and 40 μg/kg/min (p = 0.057). Neither the index of steady-state cerebral perfusion nor cerebral venous saturation were affected by dopamine infusion. Conclusion Dopamine infusion tended to improve CA capacity at low blood pressures while an index of steady-state cerebral blood flow and cerebral venous saturation were unaffected by

  16. Dopamine therapy does not affect cerebral autoregulation during hypotension in newborn piglets.

    PubMed

    Eriksen, Vibeke Ramsgaard; Rasmussen, Martin Bo; Hahn, Gitte Holst; Greisen, Gorm

    2017-01-01

    Hypotensive neonates who have been treated with dopamine have poorer neurodevelopmental outcome than those who have not been treated with dopamine. We speculate that dopamine stimulates adrenoceptors on cerebral arteries causing cerebral vasoconstriction. This vasoconstriction might lead to a rightward shift of the cerebral autoregulatory curve; consequently, infants treated with dopamine would have a higher risk of low cerebral blood flow at a blood pressure that is otherwise considered "safe". In anaesthetized piglets, perfusion of the brain, monitored with laser-doppler flowmetry, and cerebral venous saturation was measured at different levels of hypotension. Each piglet was studied in two phases: a phase with stepwise decreases in MAP and a phase with stepwise increases in MAP. We randomized the order of the two phases, whether dopamine was given in the first or second phase, and the infusion rate of dopamine (10, 25, or 40 μg/kg/min). In/deflation of a balloon catheter, placed in vena cava, induced different levels of hypotension. At each level of hypotension, fluctuations in MAP were induced by in/deflations of a balloon catheter in descending aorta. During measurements, PaCO2 and arterial saturation were stable. MAP levels ranged between 14 and 82 mmHg. Cerebral autoregulation (CA) capacity was calculated as the ratio between %-change in cerebrovascular resistance and %-change in MAP induced by the in/deflation of the arterial balloon. A breakpoint in CA capacity was identified at a MAP of 38±18 mmHg without dopamine and at 44±18, 31±14, and 24±14 mmHg with dopamine infusion rates of 10, 25, and 40 μg/kg/min (p = 0.057). Neither the index of steady-state cerebral perfusion nor cerebral venous saturation were affected by dopamine infusion. Dopamine infusion tended to improve CA capacity at low blood pressures while an index of steady-state cerebral blood flow and cerebral venous saturation were unaffected by dopamine infusion. Thus, dopamine does not

  17. Retrospective study of factors affecting employability of individuals with cerebral palsy in Japan.

    PubMed

    Tobimatsu, Y; Nakamura, R

    2000-12-01

    The purpose of this study was to investigate the characteristics of individuals with cerebral palsy that affected their ability to find a job in Japan. A retrospective nonrandomized descriptive study was performed. Subjects were 99 individuals with cerebral palsy who were eligible to have a vocational training at the National Rehabilitation Center for the Disabled after graduation from high school. All of them were able to perform ADL unassistedly. The mean age of the subjects was 19.9 years (range, 18 to 33) and the mean intelligence quotient measured by WAIS-R was 78.5 (range, 46 to 110). Walking ability, being female and experience of learning in a regular middle high school were significant explanatory variables in the multiple regression equation. The ability of individuals with cerebral palsy to get a job in Japan in the 1990's was largely determined by being able to walk and having an education in a regular school.

  18. Metallothionein 2A affects the cell respiration by suppressing the expression of mitochondrial protein cytochrome c oxidase subunit II.

    PubMed

    Bragina, Olga; Gurjanova, Karina; Krishtal, Jekaterina; Kulp, Maria; Karro, Niina; Tõugu, Vello; Palumaa, Peep

    2015-06-01

    Metallothioneins (MT) are involved in a broad range of cellular processes and play a major role in protection of cells towards various stressors. Two functions of MTs, namely the maintaining of the homeostasis of transition metal ions and the redox balance, are directly linked to the functioning of mitochondria. Dyshomeostasis of MTs is often related with malfunctioning of mitochondria; however, the mechanism by which MTs affect the mitochondrial respiratory chain is still unknown. We demonstrated that overexpression of MT-2A in HEK cell line decreased the oxidative phosphorylation capacity of the cells. HEK cells overexpressing MT-2A demonstrated reduced oxygen consumption and lower cellular ATP levels. MT-2A did not affect the number of mitochondria, but reduced specifically the level of cytochrome c oxidase subunit II protein, which resulted in lower activity of the complex IV.

  19. Argon does not affect cerebral circulation or metabolism in male humans

    PubMed Central

    Kazmaier, Stephan; Hoeks, Sanne Elisabeth; Stolker, Robert Jan; Coburn, Marc; Weyland, Andreas

    2017-01-01

    Objective Accumulating data have recently underlined argon´s neuroprotective potential. However, to the best of our knowledge, no data are available on the cerebrovascular effects of argon (Ar) in humans. We hypothesized that argon inhalation does not affect mean blood flow velocity of the middle cerebral artery (Vmca), cerebral flow index (FI), zero flow pressure (ZFP), effective cerebral perfusion pressure (CPPe), resistance area product (RAP) and the arterio-jugular venous content differences of oxygen (AJVDO2), glucose (AJVDG), and lactate (AJVDL) in anesthetized patients. Materials and methods In a secondary analysis of an earlier controlled cross-over trial we compared parameters of the cerebral circulation under 15 minutes exposure to 70%Ar/30%O2 versus 70%N2/30%O2 in 29 male patients under fentanyl-midazolam anaesthesia before coronary surgery. Vmca was measured by transcranial Doppler sonography. ZFP and RAP were estimated by linear regression analysis of pressure-flow velocity relationships of the middle cerebral artery. CPPe was calculated as the difference between mean arterial pressure and ZFP. AJVDO2, AJVDG and AJVDL were calculated as the differences in contents between arterial and jugular-venous blood of oxygen, glucose, and lactate. Statistical analysis was done by t-tests and ANOVA. Results Mechanical ventilation with 70% Ar did not cause any significant changes in mean arterial pressure, Vmca, FI, ZFP, CPPe, RAP, AJVDO2, AJVDG, and AJVDL. Discussion Short-term inhalation of 70% Ar does not affect global cerebral circulation or metabolism in male humans under general anaesthesia. PMID:28207907

  20. How the Reorganization Free Energy Affects the Reduction Potential of Structurally Homologous Cytochromes.

    PubMed

    Daidone, Isabella; Amadei, Andrea; Zaccanti, Francesco; Borsari, Marco; Bortolotti, Carlo Augusto

    2014-05-01

    Differences in the reduction potential E(0) among structurally similar metalloproteins cannot always be fully explained on the basis of their 3-D structures. We investigate the molecular determinants to E(0) using the mixed quantum mechanics/molecular mechanics approach named perturbed matrix method (PMM); after comparison with experimental values to assess the reliability of our calculations, we investigate the relationship between the change in free energy upon reduction ΔA(0) and the reorganization energy. We find that the reduction potential of cytochromes can be regarded as the result of the sum of two terms, one being mostly dependent on the energy fluctuations within a limited range around the mean transition energy and the second being mostly dependent linearly on the difference Δλ = λred - λox of the reorganization free energies for the ox → red (λred) and for the red → ox (λox) relaxations.

  1. His92 and His110 Selectively Affect Different Heme Centers of Adrenal Cytochrome b561†

    PubMed Central

    Liu, Wen; Rogge, Corina E.; da Silva, Giordano F. Z.; Shinkarev, Vladimir P.; Tsai, Ah-Lim; Kamensky, Yury; Palmer, Graham; Kulmacz, Richard J.

    2008-01-01

    Adrenal cytochrome b561 (cyt b561), a transmembrane protein that shuttles reducing equivalents derived from ascorbate, has two heme centers with distinct spectroscopic signals and reactivity towards ascorbate. The His54/His122 and His88/His161 pairs furnish axial ligands for the hemes, but additional amino acid residues contributing to the heme centers have not been identified. A computational model of human cyt b561 (Bashtovyy, D., Berczi, A., Asard, H., and Pali, T. (2003) Protoplasma 221, 31–40) predicts that His92 is near the His88/His161 heme and that His110 abuts the His54/His122 heme. We tested these predictions by analyzing the effects of mutations at His92 or His110 on the spectroscopic and functional properties. Wild type cytochrome and mutants with substitutions in other histidine residues or in Asn78 were used for comparison. The largest lineshape changes in the optical absorbance spectrum of the high-potential (bH) peak were seen with mutation of His92; the largest changes in the low-potential (bL) peak lineshape were observed with mutation of His110. In the EPR spectra, mutation of His92 shifted the position of the g=3.1 signal (bH) but not the g=3.7 signal (bL). In reductive titrations with ascorbate, mutations in His92 produced the largest increase in the midpoint for the bH transition; mutations in His110 produced the largest decreases in ΔA561 for the bL transition. These results indicate that His92 can be considered part of the bH heme center, and His110 part of the bL heme center, in adrenal cyt b561. PMID:18501187

  2. Structural analysis of tissues affected by cytochrome C oxidase deficiency due to mutations in the SCO2 gene.

    PubMed

    Vesela, Katerina; Hulkova, Helena; Hansikova, Hana; Zeman, Jiri; Elleder, Milan

    2008-01-01

    Structural and histochemical studies carried out in a series of seven cases (from five families) with isolated cytochrome c oxidase (COX) deficiency caused by mutations in the SCO2 gene (1, 2) disclosed changes concentrated in the nervous system, skeletal muscle and myocardium. In five patients homozygous for the E140K mutation, the phenotype was predominantly neuromuscular and the average life span ranged between 9 and 15 months. In two cases, the course was more rapid (death at 7 and 11 weeks of life) and featured marked cardiac hypertrophy (3- and 4-fold increase in heart weight). This predominantly cardiomyopathic phenotype was associated with compound heterozygosity (E140K with another nonsense mutation) in the SCO2 gene. Polioencephalopathy with neurodegeneration and neuronal drop out was present in all cases with evidence that retinal neurons might be seriously affected too. Involvement of spinal motoneurons together with cytochrome c oxidase deficiency in muscle represents a "double hit" for the skeletal muscle. The mitochondrial population was not found to be significantly increased or structurally altered, with the exception of two compound heterozygotes in which the cardiac mitochondria were increased in number and size. Our report extends knowledge of the pathology of COX deficiency caused by mutations in the SCO2 gene.

  3. A Mutator Affecting the Region of the Iso-1-Cytochrome c Gene in Yeast

    PubMed Central

    Liebman, Susan W.; Singh, Arjun; Sherman, Fred

    1979-01-01

    The mutator gene DEL1 in the yeast Saccharomyces cerevisiae causes a high rate of formation of multisite mutations that encompass the following three adjacent genes: CYC1, which determines the structure of iso-1-cytochrome c; RAD7, which controls UV sensitivity; and OSM1, which controls osomotic sensitivity. The simplest hypothesis is that these multisite mutations are deletions, although it has not been excluded that they may involve other types of gross chromosomal aberrations. In contrast, normal strains do not produce such multisite mutations even after mutagenic treatments.—The multisite mutations arise at a rate of approximately 10-5 to 10-6 per cell per division in DEL1 strains, which is much higher than rates observed for mutation of genes in normal strains. For example, normal strains produce all types of cyc1 mutants at a low rate of approximately 10-8 to 10-9. No evidence for multisite mutations was obtained upon analysis of numerous spontaneous ade1, ade2, met2 and met15 mutants isolated in a DEL1 strain. DEL1 segregates as a single Mendelian gene closely linked to the CYC1 locus. DEL1 appears to be both cis- and trans-dominant. The location of the DEL1 gene and the lack of effect on other genes suggest that the mutator acts only on a region adjacent to itself. PMID:231539

  4. Does light scattering affect the OCT quantitation of redox state of cytochrome oxidase in bone tissue?

    NASA Astrophysics Data System (ADS)

    Xu, Xiangqun; Wang, Ruikang K.; El Haj, Alicia

    2002-06-01

    In our previous report, we have presented the possibility of optical coherence tomography (OCT) to monitor the redox state of mitochondria enzyme Cytochrome oxidase (CytOx) in bone tissue. The previous results showed that reduction of the enzyme in periosteal tissue leads to a change in attenuation coefficient of 1.68 +/- 0.67mm-1 by OCT measurements. The new results from cultured cells fixed in 300 (mu) l agarose plug showed the difference in attenuation coefficient is 0.26+-0.10 mm-1 (n = 9) for 7x106 astrocytoma cells and 0.28+-0.13 mm-1 (n = 7) for 20x106 astrocytoma cells in agarose plug, respectively between cells with oxidised and reduced enzyme at 820nm. A decrease in attenuation coefficient of 0.35+-0.09 mm-1 (n = 4) for 10 million SKMES cells in agarose was also observed with the redox shift of CytOx. The absorption coefficient of the oxidized-reduced form of CytOx is measured approximately 8.4+-1.5x10-3/mm (n=3) and 8.2+-1.0x10-3/mm (n=3) at 820nm for astrocytoma cells and rat periosteum respectively by means of a biochemical assay. Thereby it can be seen that the change in attenuation coefficient of cultured cells with redox shift of CytOx mainly results from the scattering change.

  5. Disruption of a hydrogen bond network in human versus spider monkey cytochrome c affects heme crevice stability.

    PubMed

    Goldes, Matthew E; Jeakins-Cooley, Margaret E; McClelland, Levi J; Mou, Tung-Chung; Bowler, Bruce E

    2016-05-01

    The hypothesis that the recent rapid evolution of primate cytochromes c, which primarily involves residues in the least stable Ω-loop (Ω-loop C, residues 40-57), stabilizes the heme crevice of cytochrome c relative to other mammals, is tested. To accomplish this goal, we have compared the properties of human and spider monkey cytochrome c and a set of four variants produced in the process of converting human cytochrome c into spider monkey cytochrome c. The global stability of all variants has been measured by guanidine hydrochloride denaturation. The stability of the heme crevice has been assessed with the alkaline conformational transition. Structural insight into the effects of the five amino acid substitutions needed to convert human cytochrome c into spider monkey cytochrome c is provided by a 1.15Å resolution structure of spider monkey cytochrome c. The global stability for all variants is near 9.0kcal/mol at 25°C and pH7, which is higher than that observed for other mammalian cytochromes c. The heme crevice stability is more sensitive to the substitutions required to produce spider monkey cytochrome c with decreases of up to 0.5 units in the apparent pKa of the alkaline conformational transition relative to human cytochrome c. The structure of spider monkey cytochrome c indicates that the Y46F substitution destabilizes the heme crevice by disrupting an extensive hydrogen bond network that connects three surface loops including Ω-loop D (residues 70-85), which contains the Met80 heme ligand. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Redox state of near infrared spectroscopy-measured cytochrome aa(3) correlates with delayed cerebral energy failure following perinatal hypoxia-ischaemia in the newborn pig.

    PubMed

    Peeters-Scholte, Cacha; van den Tweel, Evelyn; Groenendaal, Floris; van Bel, Frank

    2004-05-01

    Early detection of delayed cerebral energy failure may be important in the prevention of reperfusion injury of the brain after severe perinatal hypoxia-ischaemia (HI). This study investigated whether monitoring of the redox state of cytochrome aa(3) (Cytaa(3)) with near infrared spectroscopy (NIRS) after severe perinatal asphyxia may allow us to detect early a compromised energy metabolism of the developing brain. We therefore correlated serial Cytaa(3) measurements (to estimate mitochondrial oxygenation) simultaneously with the (31)phosphorous-magnetic resonance spectroscopy ((31)P-MRS)-measured phosphocreatin/inorganic phosphate (PCr/Pi) ratio (to estimate cerebral energy reserve) in newborn piglets before and after severe hypoxia-ischaemia. The animals were treated upon reperfusion with either allopurinol, deferoxamine, or 2-iminobiotin or with a vehicle to reduce post-HI reperfusion injury of the brain. Four sham-operated piglets served as controls. Before HI, the individual Cytaa(3) values ranged between -0.02 and 0.71 micromol/L (mean value: -0.07) relative to baseline. The pattern over post-HI time of the vehicle-treated animals was remarkably different from the other groups in as far Cytaa(3) became more oxidised from 3 h after start of HI onwards (increase of Cytaa(3) as compared with baseline), whereas the other groups showed a significant reduction over time (decrease of Cytaa(3) as compared with baseline: allopurinol and deferoxamine) or hardly any change (2-iminobiotin and sham-operated piglets). Vehicle-treated piglets showed a significant reduction in PCr/Pi at 24 h after start of HI, but the cerebral energy state was preserved in 2-iminobiotin-, allopurinol- and deferoxamine-treated piglets. With severe reduction in PCr/Pi-ratio, major changes in the redox-state of Cytaa(3) also occurred: Cytaa(3) was mostly either in a reduced state (down to -6.45 micromol/L) or in an oxidised state (up to 6.84 micromol/L) at these low PCr/Pi ratios. The positive

  7. Motor, cognitive, and affective areas of the cerebral cortex influence the adrenal medulla

    PubMed Central

    Dum, Richard P.; Levinthal, David J.; Strick, Peter L.

    2016-01-01

    Modern medicine has generally viewed the concept of “psychosomatic” disease with suspicion. This view arose partly because no neural networks were known for the mind, conceptually associated with the cerebral cortex, to influence autonomic and endocrine systems that control internal organs. Here, we used transneuronal transport of rabies virus to identify the areas of the primate cerebral cortex that communicate through multisynaptic connections with a major sympathetic effector, the adrenal medulla. We demonstrate that two broad networks in the cerebral cortex have access to the adrenal medulla. The larger network includes all of the cortical motor areas in the frontal lobe and portions of somatosensory cortex. A major component of this network originates from the supplementary motor area and the cingulate motor areas on the medial wall of the hemisphere. These cortical areas are involved in all aspects of skeletomotor control from response selection to motor preparation and movement execution. The second, smaller network originates in regions of medial prefrontal cortex, including a major contribution from pregenual and subgenual regions of anterior cingulate cortex. These cortical areas are involved in higher-order aspects of cognition and affect. These results indicate that specific multisynaptic circuits exist to link movement, cognition, and affect to the function of the adrenal medulla. This circuitry may mediate the effects of internal states like chronic stress and depression on organ function and, thus, provide a concrete neural substrate for some psychosomatic illness. PMID:27528671

  8. Motor coordination and spatial orientation are affected by neurofilament maldistribution: correlations with regional brain activity of cytochrome oxidase.

    PubMed

    Lalonde, R; Dubois, M; Strazielle, C; Eyer, J

    1999-05-01

    NFH-LacZ transgenic mice are characterized by an early accumulation of the neurofilament cytoskeleton in the cell bodies of neurons with age-associated abnormalities of motor neurons and cerebellar Purkinje cells. In comparison to normal littermate controls, irrespective of age (3 and 12-20 months), NFH-LacZ transgenic mice had a lower number of rears in an open field, deficiencies in some motor-coordination tests, and a higher number of quadrant entries and escape latencies while swimming toward a visible platform. Decreased cytochrome oxidase activity in the lateral reticular nucleus of NFH-LacZ mice was associated with poor performance in two motor coordination tests. Lower metabolic activity in the lateral reticular nucleus may be secondary to previously described cerebellar abnormalities, leading to deficient motor control. The dramatic cytoskeletal perturbation characterizing NFH-LacZ mice affects only selective neuronal populations and results in selective behavioral deficits, which can be correlated with regional brain metabolic activity.

  9. A new broadband near-infrared spectroscopy system for in-vivo measurements of cerebral cytochrome-c-oxidase changes in neonatal brain injury.

    PubMed

    Bale, Gemma; Mitra, Subhabrata; Meek, Judith; Robertson, Nicola; Tachtsidis, Ilias

    2014-10-01

    We present a novel lens-based broadband near-infrared spectroscopy system to simultaneously measure cerebral changes in tissue oxygenation and haemodynamics via estimation of the changes in haemoglobin concentration; in addition to oxygen utilization via the measurement of the oxidation state of cytochrome-c-oxidase (CCO). We demonstrate the use of the system in a cohort of 6 newborn infants with neonatal encephalopathy in the Neonatal Intensive Care Unit for continuous measurement periods of up to 5 days. NIRS data was collected from above the frontal lobe on the left and right hemispheres simultaneously with systemic data to allow multimodal data analysis. This allowed us to study the NIRS variables in response to global pathophysiological events and we focused our analysis to spontaneous oxygen desaturations. We identified changes from the NIRS variables during 236 oxygen desaturations from over 212 hours of data with a change from the baseline to nadir of -12 ± 3%. There was a consistent negative change in the Δ[HbD] (= oxygenated - deoxygenated haemoglobin) and Δ[oxCCO] measurements, mean decreases were 3.0 ± 1.7μM and 0.22 ± 0.11μM, and a positive change in the Δ[HbT] (= oxygenated + deoxygenated haemoglobin) measurements across all subjects, mean increase was 0.85 ± 0.58μM. We have shown with a feasibility study that the relationship between haemoglobin oxygenation changes and CCO oxidation changes during these desaturation events was significantly associated with a magnetic resonance spectroscopy (MRS)-measured biomarker of injury severity (r = 0.91, p<0.01).

  10. Effectiveness of adaptive pretend play on affective expression and imagination of children with cerebral palsy.

    PubMed

    Hsieh, Hsieh-Chun

    2012-01-01

    Children with cerebral palsy (CP) have difficulty participating in role-pretending activities. The concept of adaptive play makes play accessible by modifying play materials for different needs or treatment goals for children with CP. This study examines the affective expressions and imagination in children with CP as a function of ordinary versus adaptive pretend play. The Affect in Play Scale-Brief Rating measured the affective expression and imagination for 29 children with CP and 29 typically developing children (mean age=7.34 years). Two groups of children were observed while playing with a standard set of ordinary toys for ten times and with a standard procedure of adaptive pretend play for ten times. The results show significantly different affective expressions and imagination between the two groups. Typically developing children displayed much more affective expression and imagination. However, a more positive influence of affective expression and imagination occurred in children with CP than in typically developing children. In repeated measures analysis, the frequency of positive affective expression and imagination of children with CP was higher when pretending with adaptive toys. Adaptive pretend play can promote more role-pretending behaviors and a sense of environmental control during the manipulating process for children with CP. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Very-low-frequency oscillations of cerebral hemodynamics and blood pressure are affected by aging and cognitive load.

    PubMed

    Vermeij, Anouk; Meel-van den Abeelen, Aisha S S; Kessels, Roy P C; van Beek, Arenda H E A; Claassen, Jurgen A H R

    2014-01-15

    Spontaneous slow oscillations occur in cerebral hemodynamics and blood pressure (BP), and may reflect neurogenic, metabolic or myogenic control of the cerebral vasculature. Aging is accompanied by a degeneration of the vascular system, which may have consequences for regional cerebral blood flow and cognitive performance. This degeneration may be reflected in a reduction of spontaneous slow oscillations of cerebral hemodynamics and BP. Therefore, we aimed to establish the dependency of slow oscillations of cerebral hemodynamics and BP on the factors age and cognitive load, by using functional near-infrared spectroscopy (fNIRS). Fourteen healthy young (23-32 years) and 14 healthy older adults (64-78 years) performed a verbal n-back working-memory task. Oxygenated and deoxygenated hemoglobin concentration changes were registered by two fNIRS channels located over left and right prefrontal cortex. BP was measured in the finger by photoplethysmography. We found that very-low-frequency oscillations (0.02-0.07 Hz) and low-frequency oscillations (0.07-0.2 Hz) of cerebral hemodynamics and BP were reduced in the older adults compared to the young during task performance. In young adults, very-low-frequency oscillations of cerebral hemodynamics and BP reduced with increased cognitive load. Cognitive load did not affect low-frequency oscillations of the cerebral hemodynamics and BP. Transfer function analysis indicated that the relationship between BP and cerebral hemodynamic oscillations does not change under influence of age and cognitive load. Our results suggest aging-related changes in the microvasculature such as declined spontaneous activity in microvascular smooth muscle cells and vessel stiffness. Moreover, our results indicate that in addition to local vasoregulatory processes, systemic processes also influence cerebral hemodynamic signals. It is therefore crucial to take the factors age and BP into consideration for the analysis and interpretation of hemodynamic

  12. Significant proteins affecting cerebral vasospasm using complementary ICPMS and MALDI-MS.

    PubMed

    Easter, Renee N; Barry, Colin G; Pyne-Geithman, Gail; Caruso, Joseph A

    2012-01-01

    Cerebral vasospasm (CV) following subarachnoid hemorrhagic stroke affects more than one million people each year. The etiology and prevention of CV is currently of great interest to researchers in various fields of medical science. More recently, the idea that selenium could be playing a major role in the onset of cerebral vasospasm has come into the spotlight. This study focused on using newly established metallomics techniques in order to explore the proteome associated with CV and if selenium might affect the discovered proteins. Size exclusion chromatography coupled to inductively coupled plasma mass spectrometry, along with LC-MALDI-TOF/TOF were both essential in determining protein identifications in three different sample types; a control (normal, healthy patient, CSF control), SAH stroke patients (no vasospasm, CSF C) and SAH CV patients (CSF V). The results of this study, although preliminary, indicate the current methods are applicable and warrant further application to these clinically important targets. This journal is © The Royal Society of Chemistry 2012

  13. Factors Affecting Cerebral Oxygenation in Hemodialysis Patients: Cerebral Oxygenation Associates with pH, Hemodialysis Duration, Serum Albumin Concentration, and Diabetes Mellitus

    PubMed Central

    Ito, Kiyonori; Ookawara, Susumu; Ueda, Yuichiro; Goto, Sawako; Miyazawa, Haruhisa; Yamada, Hodaka; Kitano, Taisuke; Shindo, Mitsunobu; Kaku, Yoshio; Hirai, Keiji; Yoshida, Masashi; Hoshino, Taro; Nabata, Aoi; Mori, Honami; Yoshida, Izumi; Kakei, Masafumi; Tabei, Kaoru

    2015-01-01

    Background Patients undergoing hemodialysis (HD) often develop cerebral disease complications. Furthermore, cerebral regional saturation of oxygen (rSO2) was previously reported to be significantly lower in HD patients than in healthy subjects. We aimed to identify the factors affecting the cerebral rSO2 in HD patients. Methods Fifty-four HD patients (38 men and 16 women; mean age, 67.7 ± 1.2 years, HD duration, 6.5 ± 1.9 years) were recruited. Cerebral rSO2 was monitored at the forehead before HD using an INVOS 5100C (Covidien Japan, Tokyo, Japan). Results The rSO2 levels were significantly lower in HD patients compared with healthy controls (49.5 ± 1.7% vs. 68.9 ± 1.6%, p <0.001). Multiple regression analysis showed that cerebral rSO2 independently associated with pH (standardized coefficient: -0.35), HD duration (standardized coefficient: -0.33), and serum albumin concentration (standardized coefficient: 0.28). Furthermore, the rSO2 was significantly lower in HD patients with diabetes mellitus (DM), compared with patients without DM (46.8 ± 1.7% vs. 52.1 ± 1.8%, p <0.05). Conclusions In HD patients, cerebral rSO2 was affected by multiple factors, including pH, HD duration, and serum albumin concentration. Furthermore, this is the first report describing significantly lower levels of rSO2 in HD patients with DM than in those without DM. PMID:25706868

  14. Cognitive tasks during walking affect cerebral blood flow signal features in middle cerebral arteries and their correlation to gait characteristics.

    PubMed

    Gatouillat, Arthur; Bleton, Héloïse; VanSwearingen, Jessie; Perera, Subashan; Thompson, Scott; Smith, Traci; Sejdić, Ervin

    2015-09-26

    Gait is a complex process involving both cognitive and sensory ability and is strongly impacted by the environment. In this paper, we propose to study of the impact of a cognitive task during gait on the cerebral blood flow velocity, the blood flow signal features and the correlation of gait and blood flow features through a dual task methodology. Both cerebral blood flow velocity and gait characteristics of eleven participants with no history of brain or gait conditions were recorded using transcranial Doppler on mid-cerebral artery while on a treadmill. The cognitive task was induced by a backward counting starting from 10,000 with decrement of 7. Central blood flow velocity raw and envelope features were extracted in both time, frequency and time-scale domain; information-theoretic metrics were also extracted and statistical significances were inspected. A similar feature extraction was performed on the stride interval signal. Statistical differences between the cognitive and baseline trials, between the left and right mid-cerebral arteries signals and the impact of the antropometric variables where studied using linear mixed models. No statistical differences were found between the left and right mid-cerebral arteries flows or the baseline and cognitive state gait features, while statistical differences for specific features were measured between cognitive and baseline states. These statistical differences found between the baseline and cognitive states show that cognitive process has an impact on the cerebral activity during walking. The state was found to have an impact on the correlation between the gait and blood flow features.

  15. Altered Cerebral Perfusion in Executive, Affective, and Motor Networks During Adolescent Depression

    PubMed Central

    Ho, Tiffany C.; Wu, Jing; Shin, David D.; Liu, Thomas T.; Tapert, Susan F.; Yang, Guang; Connolly, Colm G.; Frank, Guido K.W.; Max, Jeffrey E.; Wolkowitz, Owen; Eisendrath, Stuart; Hoeft, Fumiko; Banerjee, Dipavo; Hood, Korey; Hendren, Robert L.; Paulus, Martin P.; Simmons, Alan N.; Yang, Tony T.

    2013-01-01

    Objective While substantial literature has reported regional cerebral blood flow (rCBF) abnormalities in adults with depression, these studies commonly necessitated the injection of radioisotopes into subjects. The recent development of arterial spin labeling (ASL), however, allows for noninvasive measurements of rCBF. Currently, no published ASL studies have examined cerebral perfusion in adolescents with depression. Thus, the aim of the present study was to examine baseline cerebral perfusion in adolescent depression using a newly developed ASL technique: pseudocontinuous arterial spin labeling (PCASL). Method 25 medication-naive adolescents (ages 13–17 years) diagnosed with major depressive disorder (MDD) and 26 well-matched controls underwent functional magnetic resonance imaging. Baseline rCBF was measured via a novel PCASL method that optimizes tagging efficiency. Results Voxel-based whole brain analyses revealed significant frontal, limbic, paralimbic, and cingulate hypoperfusion in the group with depression (p<0.05, corrected). Hyperperfusion was also observed within the subcallosal cingulate, putamen, and fusiform gyrus (p<0.05, corrected). Similarly, region-of-interest analyses revealed amygdalar and insular hypoperfusion in the group with depression, as well as hyperperfusion in the putamen and superior insula (p<0.05, corrected). Conclusions Adolescents with depression and healthy adolescents appear to differ on rCBF in executive, affective, and motor networks. Dysfunction in these regions may contribute to the cognitive, emotional, and psychomotor symptoms commonly present in adolescent depression. These findings point to possible biomarkers for adolescent depression that could inform early interventions and treatments and establishes a methodology for using PCASL to noninvasively measure rCBF in clinical and healthy adolescent populations. PMID:24074474

  16. Cerebral Palsy

    MedlinePlus

    ... ol (Spanish) Recommend on Facebook Tweet Share Compartir Cerebral palsy (CP) is a group of disorders that affect ... resource—it highlights the ADDM Network’s data on cerebral palsy in a way that is useful for stakeholders ...

  17. Cerebral Palsy

    MedlinePlus

    Cerebral palsy is a group of disorders that affect a person's ability to move and to maintain balance ... do not get worse over time. People with cerebral palsy may have difficulty walking. They may also have ...

  18. Sitting postural control affects the development of focused attention in children with cerebral palsy.

    PubMed

    Surkar, Swati M; Edelbrock, Christina; Stergiou, Nicholas; Berger, Sarah; Harbourne, Regina

    2015-01-01

    To investigate whether focused attention (FA) changes over time as sitting postural control improves and whether an impairment in sitting postural control affects the development of FA in children with cerebral palsy (CP). Nineteen children with CP, mean ages 21.47 months, were assessed for FA and sitting scores pre- and postintervention. Longest, total, and global FA increased and frequency of FA decreased in children who achieved independent sitting. However, children who achieved mobility postintervention exhibited a decrease in longest FA and an increase in frequency of FA. Sitting postural control and the development of FA appear associated in children with CP. The increase in FA may signal a key opportunity for learning and attending to objects. However, the time of early mobility may interrupt these long periods of attention, resulting in less sustained attention to objects.

  19. Noise affects speech-signal processing differently in the cerebral hemispheres.

    PubMed

    Shtyrov, Y; Kujala, T; Ilmoniemi, R J; Näätänen, R

    1999-07-13

    This study explored the effects of acoustic noise on the cerebral asymmetry of speech perception. We measured magnetic fields of the brain elicited by consonant-vowel syllables in silence and white noise. Background noise affected brain responses to these stimuli differently in the left and right auditory cortices. Its depressive effect on cortical responses was found mainly in the left hemisphere, whereas the right hemisphere was unaffected or exhibited increased activity in noise. Locations of the P1, N1, and P2 activity sources in noise were different from those in silence in the right but not in the left hemisphere. These results suggest an increased right hemisphere role in speech sound processing in noisy conditions, involving the recruitment of additional right auditory cortex structures.

  20. Cerebral White Matter Lesions and Affective Episodes Correlate in Male Individuals with Bipolar Disorder

    PubMed Central

    Birner, Armin; Seiler, Stephan; Lackner, Nina; Bengesser, Susanne A.; Queissner, Robert; Fellendorf, Frederike T.; Platzer, Martina; Ropele, Stefan; Enzinger, Christian; Schwingenschuh, Petra; Mangge, Harald; Pirpamer, Lukas; Deutschmann, Hannes; McIntyre, Roger S.; Kapfhammer, Hans-Peter; Reininghaus, Bernd; Reininghaus, Eva Z.

    2015-01-01

    Background Cerebral white matter lesions (WML) have been found in normal aging, vascular disease and several neuropsychiatric conditions. Correlations of WML with clinical parameters in BD have been described, but not with the number of affective episodes, illness duration, age of onset and Body Mass Index in a well characterized group of euthymic bipolar adults. Herein, we aimed to evaluate the associations between bipolar course of illness parameters and WML measured with volumetric analysis. Methods In a cross-sectional study 100 euthymic individuals with BD as well as 54 healthy controls (HC) were enrolled to undergo brain magnetic resonance imaging using 3T including a FLAIR sequence for volumetric assessment of WML-load using FSL-software. Additionally, clinical characteristics and psychometric measures including Structured Clinical Interview according to DSM-IV, Hamilton-Depression, Young Mania Rating Scale and Beck’s Depression Inventory were evaluated. Results Individuals with BD had significantly more (F = 3.968, p < .05) WML (Mdn = 3710mm3; IQR = 2961mm3) than HC (Mdn = 2185mm3; IQR = 1665mm3). BD men (Mdn = 4095mm3; IQR = 3295mm3) and BD women (Mdn = 3032mm3; IQR = 2816mm3) did not significantly differ as to the WML-load or the number and type of risk factors for WML. However, in men only, the number of manic/hypomanic episodes (r = 0.72; p < .001) as well as depressive episodes (r = 0.51; p < .001) correlated positively with WML-load. Conclusions WML-load strongly correlated with the number of manic episodes in male BD patients, suggesting that men might be more vulnerable to mania in the context of cerebral white matter changes. PMID:26252714

  1. Reduced short term adaptation to robot generated dynamic environment in children affected by Cerebral Palsy

    PubMed Central

    2011-01-01

    Background It is known that healthy adults can quickly adapt to a novel dynamic environment, generated by a robotic manipulandum as a structured disturbing force field. We suggest that it may be of clinical interest to evaluate to which extent this kind of motor learning capability is impaired in children affected by cerebal palsy. Methods We adapted the protocol already used with adults, which employs a velocity dependant viscous field, and compared the performance of a group of subjects affected by Cerebral Palsy (CP group, 7 subjects) with a Control group of unimpaired age-matched children. The protocol included a familiarization phase (FA), during which no force was applied, a force field adaptation phase (CF), and a wash-out phase (WO) in which the field was removed. During the CF phase the field was shut down in a number of randomly selected "catch" trials, which were used in order to evaluate the "learning index" for each single subject and the two groups. Lateral deviation, speed and acceleration peaks and average speed were evaluated for each trajectory; a directional analysis was performed in order to inspect the role of the limb's inertial anisotropy in the different experimental phases. Results During the FA phase the movements of the CP subjects were more curved, displaying greater and variable directional error; over the course of the CF phase both groups showed a decreasing trend in the lateral error and an after-effect at the beginning of the wash-out, but the CP group had a non significant adaptation rate and a lower learning index, suggesting that CP subjects have reduced ability to learn to compensate external force. Moreover, a directional analysis of trajectories confirms that the control group is able to better predict the force field by tuning the kinematic features of the movements along different directions in order to account for the inertial anisotropy of arm. Conclusions Spatial abnormalities in children affected by cerebral palsy may be

  2. Reduced short term adaptation to robot generated dynamic environment in children affected by Cerebral Palsy.

    PubMed

    Masia, Lorenzo; Frascarelli, Flaminia; Morasso, Pietro; Di Rosa, Giuseppe; Petrarca, Maurizio; Castelli, Enrico; Cappa, Paolo

    2011-05-21

    It is known that healthy adults can quickly adapt to a novel dynamic environment, generated by a robotic manipulandum as a structured disturbing force field. We suggest that it may be of clinical interest to evaluate to which extent this kind of motor learning capability is impaired in children affected by cerebal palsy. We adapted the protocol already used with adults, which employs a velocity dependant viscous field, and compared the performance of a group of subjects affected by Cerebral Palsy (CP group, 7 subjects) with a Control group of unimpaired age-matched children. The protocol included a familiarization phase (FA), during which no force was applied, a force field adaptation phase (CF), and a wash-out phase (WO) in which the field was removed. During the CF phase the field was shut down in a number of randomly selected "catch" trials, which were used in order to evaluate the "learning index" for each single subject and the two groups. Lateral deviation, speed and acceleration peaks and average speed were evaluated for each trajectory; a directional analysis was performed in order to inspect the role of the limb's inertial anisotropy in the different experimental phases. During the FA phase the movements of the CP subjects were more curved, displaying greater and variable directional error; over the course of the CF phase both groups showed a decreasing trend in the lateral error and an after-effect at the beginning of the wash-out, but the CP group had a non significant adaptation rate and a lower learning index, suggesting that CP subjects have reduced ability to learn to compensate external force. Moreover, a directional analysis of trajectories confirms that the control group is able to better predict the force field by tuning the kinematic features of the movements along different directions in order to account for the inertial anisotropy of arm. Spatial abnormalities in children affected by cerebral palsy may be related not only to disturbance in

  3. Seat surface inclination may affect postural stability during Boccia ball throwing in children with cerebral palsy.

    PubMed

    Tsai, Yung-Shen; Yu, Yi-Chen; Huang, Po-Chang; Cheng, Hsin-Yi Kathy

    2014-12-01

    The aim of the study was to examine how seat surface inclination affects Boccia ball throwing movement and postural stability among children with cerebral palsy (CP). Twelve children with bilateral spastic CP (3 with gross motor function classification system Level I, 5 with Level II, and 4 with Level III) participated in this study. All participants underwent pediatric reach tests and ball throwing performance analyses while seated on 15° anterior- or posterior-inclined, and horizontal surfaces. An electromagnetic motion analysis system was synchronized with a force plate to assess throwing motion and postural stability. The results of the pediatric reach test (p = 0.026), the amplitude of elbow movement (p = 0.036), peak vertical ground reaction force (PVGRF) (p < 0.001), and movement range of the center of pressure (COP) (p < 0.020) were significantly affected by seat inclination during throwing. Post hoc comparisons showed that anterior inclination allowed greater amplitude of elbow movement and PVGRF, and less COP movement range compared with the other inclines. Posterior inclination yielded less reaching distance and PVGRF, and greater COP movement range compared with the other inclines. The anterior-inclined seat yielded superior postural stability for throwing Boccia balls among children with bilateral spastic CP, whereas the posterior-inclined seat caused difficulty.

  4. Factors affecting protein transfer into surfactant-isooctane solution: a case study of extraction behavior of chemically modified cytochrome c.

    PubMed

    Ono, T; Goto, M

    1998-01-01

    The extraction mechanism of proteins by surfactant molecules in an organic solvent has been investigated using a chemically modified protein. We conducted guanidylation on lysine residues of cytochrome c by replacing their amino groups with homoarginine to enhance the protein-surfactant interaction. Results have shown that guanidylated cytochrome c readily forms a hydrophobic complex with dioleyl phosphoric acid (DOLPA) through hydrogen bonding between the phosphate moiety and the guanidinium groups. Although improved protein-surfactant interaction activated the formation of a hydrophobic complex at the interface, it could not improve the protein transfer in isooctane. It has been established that the protein extraction mechanism using surfactant molecules is mainly governed by two processes: formation of an interfacial complex at the oil-water interface and the subsequent solubilization of the complex into the organic phase. In addition, a kinetic study demonstrated that guanidylation of lysine accelerated the initial extraction rate of cytochrome c. This fact implies that the protein transferability from aqueous phase into organic phase depends on the protein-surfactant interaction which can be modified by protein surface engineering.

  5. Overuse of paracetamol caffeine aspirin powders affects cerebral glucose metabolism in chronic migraine patients.

    PubMed

    Di, W; Shi, X; Zhu, Y; Tao, Y; Qi, W; Luo, N; Xiao, Z; Yi, C; Miao, J; Zhang, A; Zhang, X; Fang, Y

    2013-04-01

    Overuse of analgesic plays a prominent role in migraine chronification. Paracetamol caffeine aspirin (PCA) powders are commonly used in Chinese migraineurs. This study investigated the effects of the specific combination analgesic on cerebral glucose metabolism in chronic migraine (CM). 18F-FDG-PET was used to measure regional metabolism in all subjects. Brain metabolisms of CM patients with analgesic overuse (AO-CM; n=10), no analgesic overuse (NAO-CM; n=10), and no regimen (NR-CM; n=10) and 17 age- and gender-matched normal controls (NC) were compared using statistical parametric mapping. Then, all patients underwent brain MRI analysis within 7 days after PET scans, as well as MMSE and MoCA scale for cognitive function tests. Glucose metabolic changes in CM patients taking different dosage of analgesic during headache-free periods and clear distinctions in several brain regions were observed. Patients with AO-CM exhibited significant metabolic reductions in thalamus, as well as increased metabolism in middle temporal gyrus and insula relative to NR-CM and NAO-CM. However, in these regions, no difference was observed in AO-CM except for increased metabolism in the right insula relative to NC group. Overusing PCA powders affects regional brain glucose metabolism in CM. Increased metabolism in the right insula may be associated with recurrently overusing of PCA powders. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

  6. Children with unilateral cerebral palsy show diminished implicit motor imagery with the affected hand.

    PubMed

    Jongsma, Marijtje L A; Baas, C Marjolein; Sangen, Anouk F M; Aarts, Pauline B M; van der Lubbe, Rob H J; Meulenbroek, Ruud G J; Steenbergen, Bert

    2016-03-01

    Motor imagery refers to the mental simulation of a motor action without producing an overt movement. Implicit motor imagery can be regarded as a first-person kinesthetic perceptual judgement, and addresses the capacity to engage into the manipulation of one's body schema. In this study, we examined whether children with unilateral cerebral palsy (CP) are able to engage in implicit motor imagery. A modified version of the hand laterality judgment task was employed. Erroneous responses, reaction times, and event-related potentials from the electroencephalograph were analysed. In 13 children with typical development (mean age 10y 7mo, SD 1y 2mo; seven male, six female), we observed the classic rotation direction effect. Specifically, when comparing outward rotated with inward rotated hand pictures, decreased accuracy and increased response times were observed. Event-related potentials analyses of the electroencephalogram revealed a more marked N1 and an enhanced rotation-related negativity. These findings suggest that an implicit motor imagery strategy was used to solve the task. However, in 10 children with unilateral CP (mean age 10y 7mo, SD 2y 5mo; five male, five female), these effects were observed only when the less-affected hand was involved. This observation suggests that children with CP could benefit from visual training strategies. © 2015 Mac Keith Press.

  7. Cerebral Palsy (For Parents)

    MedlinePlus

    ... 10 Tips for Parents Healthy Habits for TV, Video Games, and the Internet Cerebral ... cerebral Cerebral palsy (CP) is a disorder that affects muscle tone, movement, and motor skills (the ability to move in a coordinated and ...

  8. Cytochrome f

    SciTech Connect

    Soriano, G.M.; Smith, J.L.; Cramer, W.A.

    2001-07-17

    Cytochrome f (f, folium, leaf), a c-type cytochrome with a characteristic CysXXCysHis amino acid sequence for heme ligation, is the largest of the four major protein subunits of the membrane-embedded cytochrome b{sub 6}{sup f} complex of oxygenic photosynthesis. It contains 285-86 amino acids, consisting of a soluble 250-residue domain on the p-side (positive-side) or lumen-side of the membrane, a single trans-membrane 20-residue {alpha}-helix, and an n- or stromal-side segment consisting of 15 residues. These domains contain, respectively, the heme prosthetic group and intraprotein electron transfer pathway, the membrane anchor and a short segment that is important in the assembly of the b{sub 6}{sup f} complex. The function of the cytochrome f in oxygenic photosynthesis is to act as the terminal electron acceptor in the membrane-embedded cytochrome b{sub 6}{sup f} complex that provides the electron transport connection between the photosystem II and photosystem I reaction centers. Electron transfer through the complex is coupled to proton translocation and generation of a proton electrochemical potential that is utilized to drive the synthesis of ATP through the proton-motive ATP synthase. These functions of the cytochrome b{sub 6}{sup f} complex are analogous to those of the multisubunit cytochrome bc{sub 1} complex (ubiquinol:cytochrome c oxidoreductase) of the mitochondrial respiratory chain and photosynthetic bacteria. Both complexes contain four redox centers with very similar redox and structural properties: a covalently bound c-type heme in cytochrome f or c{sub 1}, the 2Fe-2S cluster of the Rieske ISP, and the two noncovalently bound hemes of cytochrome b. The structure properties have been defined in 3.0-3.1 {angstrom} structures of the b{sub 6}{sup f} complex from a thermophilic cyanobacterium and a green alga. These structures also defined a fifth redox prosthetic group, a novel covalently bound heme, tentatively called heme x. With the exception of

  9. Brown propolis attenuates cerebral ischemia-induced oxidative damage via affecting antioxidant enzyme system in mice.

    PubMed

    Bazmandegan, Gholamreza; Boroushaki, Mohammad Taher; Shamsizadeh, Ali; Ayoobi, Fatemeh; Hakimizadeh, Elham; Allahtavakoli, Mohammad

    2017-01-01

    Oxidative stress plays a critical role in ischemic brain injury. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) are the enzymes underlying the endogenous antioxidant mechanisms affected by stroke and are considered as oxidative stress biomarkers. Brown propolis (BP) is a bioactive natural product with a set of biological activities that in turn may differ depending on the area from which the substance is originated. The aim of this study was to investigate the effect of water-extracted brown propolis (WEBPs), from two regions of Iran, against cerebral ischemia-induced oxidative injury in a mouse model of stroke. Experimentally, the chemical characterization and total polyphenol content were determined using GC/MS and Folin-Ciocalteu assay respectively. Seventy-two adult male mice were randomly divided into the surgical sham group, control group (treated with vehicle), and four groups of WEBPs-treated animals. The WEBPs were administered at the doses of 100 and 200mg/kg IP, during four different time points. Oxidative stress biomarkers (SOD and GPx activity, SOD/GPx ratio), lipid peroxidation (LPO) index (malondialdehyde content) and infarct volume were measured 48h post stroke. Behavioral tests were evaluated 24 and 48h after stroke. WEBPs treatment resulted in significant restoration of antioxidant enzymes activity and a subsequent decrease in LPO as well as the infarct volume compared to the control group. Sensory-motor impairment and neurological deficits were improved significantly as well. These results indicate that Iranian BP confers neuroprotection on the stroke-induced neuronal damage via an antioxidant mechanism which seems to be mediated by the endogenous antioxidant system. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. MicroRNAs affect BCL-2 family proteins in the setting of cerebral ischemia.

    PubMed

    Ouyang, Yi-Bing; Giffard, Rona G

    2014-11-01

    The BCL-2 family is centrally involved in the mechanism of cell death after cerebral ischemia. It is well known that the proteins of the BCL-2 family are key regulators of apoptosis through controlling mitochondrial outer membrane permeabilization. Recent findings suggest that many BCL-2 family members are also directly involved in controlling transmission of Ca(2+) from the endoplasmic reticulum (ER) to mitochondria through a specialization called the mitochondria-associated ER membrane (MAM). Increasing evidence supports the involvement of microRNAs (miRNAs), some of them targeting BCL-2 family proteins, in the regulation of cerebral ischemia. In this mini-review, after highlighting current knowledge about the multiple functions of BCL-2 family proteins and summarizing their relationship to outcome from cerebral ischemia, we focus on the regulation of BCL-2 family proteins by miRNAs, especially miR-29 which targets multiple BCL-2 family proteins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Increased cerebral blood flow during hypercapnia is not affected by lesion of the nucleus locus ceruleus

    SciTech Connect

    Harik, S.I.; Prado, R.; Busto, R.; Ginsberg, M.D.

    1986-11-01

    To test the hypothesis that the putative noradrenergic innervation of intraparenchymal cerebral blood vessels from the nucleus locus ceruleus mediates the vasodilatory response to hypercapnia, regional cerebral blood flow was measured by iodo-(/sup 14/C)antipyrine autoradiography in awake and restrained rats with unilateral 6-hydroxydopamine lesion of the nucleus locus ceruleus and in unlesioned control rats. Hypercapnia, induced by the inhalation of 5% or 8% CO/sub 2/ in air for 8 minutes caused a 2 to 5-fold increase in regional cerebral blood flow. However, despite a marked reduction of about 90% in cortical norepinephrine levels ipsilateral to the lesion, blood flow to the frontal and parietal cortex, hippocampus, striatum and cerebellum increased to the same extent in ipsilateral and contralateral regions. Thus, lesion of the locus ceruleus and the resultant depletion of endogenous cortical and hippocampal norepinephrine, does not influence the cerebrovascular response to hypercapnia.

  12. Subtle Change in the Charge Distribution of Surface Residues May Affect the Secondary Functions of Cytochrome c*

    PubMed Central

    Paul, Simanta Sarani; Sil, Pallabi; Haldar, Shubhasis; Mitra, Samaresh; Chattopadhyay, Krishnananda

    2015-01-01

    Although the primary function of cytochrome c (cyt c) is electron transfer, the protein caries out an additional secondary function involving its interaction with membrane cardiolipin (CDL), its peroxidase activity, and the initiation of apoptosis. Whereas the primary function of cyt c is essentially conserved, its secondary function varies depending on the source of the protein. We report here a detailed experimental and computational study, which aims to understand, at the molecular level, the difference in the secondary functions of cyt c obtained from horse heart (mammalian) and Saccharomyces cerevisiae (yeast). The conformational landscape of cyt c has been found to be heterogeneous, consisting of an equilibrium between the compact and extended conformers as well as the oligomeric species. Because the determination of relative populations of these conformers is difficult to obtain by ensemble measurements, we used fluorescence correlation spectroscopy (FCS), a method that offers single-molecule resolution. The population of different species is found to depend on multiple factors, including the protein source, the presence of CDL and urea, and their concentrations. The complex interplay between the conformational distribution and oligomerization plays a crucial role in the variation of the pre-apoptotic regulation of cyt c observed from different sources. Finally, computational studies reveal that the variation in the charge distribution at the surface and the charge reversal sites may be the key determinant of the conformational stability of cyt c. PMID:25873393

  13. Does Surgical Management of the Hand in Children with Spastic Unilateral Cerebral Palsy Affect Functional Outcome?

    ERIC Educational Resources Information Center

    van Munster, Judith C.; Maathuis, Karel G. B.; Haga, Nienke; Verheij, Nienke P.; Nicolai, Jean-Philippe A.; Hadders-Algra, Mijna

    2007-01-01

    The aim of this review was to examine the literature on the effects of surgery of the spastic hand in children with cerebral palsy on functional outcome and muscle coordination. We performed a search of the relevant literature in Medline, Embase, and Biological Abstracts from 1966 to June 2006. The search resulted in eight studies on the effect of…

  14. Does Surgical Management of the Hand in Children with Spastic Unilateral Cerebral Palsy Affect Functional Outcome?

    ERIC Educational Resources Information Center

    van Munster, Judith C.; Maathuis, Karel G. B.; Haga, Nienke; Verheij, Nienke P.; Nicolai, Jean-Philippe A.; Hadders-Algra, Mijna

    2007-01-01

    The aim of this review was to examine the literature on the effects of surgery of the spastic hand in children with cerebral palsy on functional outcome and muscle coordination. We performed a search of the relevant literature in Medline, Embase, and Biological Abstracts from 1966 to June 2006. The search resulted in eight studies on the effect of…

  15. Lack of cytochrome c in Arabidopsis decreases stability of Complex IV and modifies redox metabolism without affecting Complexes I and III.

    PubMed

    Welchen, Elina; Hildebrandt, Tatjana M; Lewejohann, Dagmar; Gonzalez, Daniel H; Braun, Hans-Peter

    2012-07-01

    We studied the role of cytochrome c (CYTc), which mediates electron transfer between Complexes III and IV, in cellular events related with mitochondrial respiration, plant development and redox homeostasis. We analyzed single and double homozygous mutants in both CYTc-encoding genes from Arabidopsis: CYTC-1 and CYTC-2. While individual mutants were similar to wild-type, knock-out of both genes produced an arrest of embryo development, showing that CYTc function is essential at early stages of plant development. Mutants in which CYTc levels were extremely reduced respective to wild-type had smaller rosettes with a pronounced decrease in parenchymatic cell size and an overall delay in development. Mitochondria from these mutants had lower respiration rates and a relative increase in alternative respiration. Furthermore, the decrease in CYTc severely affected the activity and the amount of Complex IV, without affecting Complexes I and III. Reactive oxygen species levels were reduced in these mutants, which showed induction of genes encoding antioxidant enzymes. Ascorbic acid levels were not affected, suggesting that a small amount of CYTc is enough to support its normal synthesis. We postulate that, in addition to its role as an electron carrier between Complexes III and IV, CYTc influences Complex IV levels in plants, probably reflecting a role of this protein in Complex IV stability. This double function of CYTc most likely explains why it is essential for plant survival. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Do GSM 900MHz signals affect cerebral blood circulation? A near-infrared spectrophotometry study

    NASA Astrophysics Data System (ADS)

    Wolf, Martin; Haensse, Daniel; Morren, Geert; Froehlich, Juerg

    2006-06-01

    Effects of GSM 900MHz signals (EMF) typical for a handheld mobile phone on the cerebral blood circulation were investigated using near-infrared spectrophotometry (NIRS) in a three armed (12W/kg, 1.2W/kg, sham), double blind, randomized crossover trial in 16 healthy volunteers. During exposure we observed borderline significant short term responses of oxyhemoglobin and deoxyhemoglobin concentration, which correspond to a decrease of cerebral blood flow and volume and were smaller than regular physiological changes. Due to the relatively high number of statistical tests, these responses may be spurious and require further studies. There was no detectable dose-response relation or long term response within 20min. The detection limit was a fraction of the regular physiological changes elicited by functional activation. Compared to previous studies using PET, NIRS provides a much higher time resolution, which allowed investigating the short term effects efficiently, noninvasively, without the use of radioactive tracers and with high sensitivity.

  17. Phenobarbital and neonatal seizures affect cerebral oxygen metabolism: a near-infrared spectroscopy study

    PubMed Central

    Sokoloff, Max D.; Plegue, Melissa A.; Chervin, Ronald D.; Barks, John D.E.; Shellhaas, Renée A.

    2014-01-01

    Background Near-infrared spectroscopy (NIRS) measures oxygen metabolism and is increasingly used for monitoring critically-ill neonates. The implications of NIRS-recorded data in this population are poorly understood. We evaluated NIRS monitoring for neonates with seizures. Methods In neonates monitored with video-EEG, NIRS-measured cerebral regional oxygen saturation (rSO2) and systemic O2 saturation were recorded every 5 seconds. Mean rSO2 was extracted for 1-hour blocks before, during, and after phenobarbital doses. For each electrographic seizure, mean rSO2 was extracted for a period of 3-times the duration of the seizure before and after the ictal pattern, and during the seizure. Linear mixed models were developed to assess the impact of phenobarbital administration and of seizures on rSO2 and fractional tissue oxygen extraction (FTOE). Results For 20 neonates (EGA 39.6±1.5 weeks), 61 phenobarbital doses and 40 seizures were analyzed. Cerebral rSO2 rose (p=0.005), and FTOE declined (p=0.018) with increasing phenobarbital doses. rSO2 declined during seizures, compared with baseline and post-ictal phases (baseline 81.2 vs. ictal 77.7 vs. post-ictal 79.4; p=0.004). FTOE was highest during seizures (p=0.002). Conclusions Cerebral oxygen metabolism decreases after phenobarbital administration and increases during seizures. These small, but clear, changes in cerebral oxygen metabolism merit assessment for potential clinical impact. PMID:25812123

  18. Phenobarbital and neonatal seizures affect cerebral oxygen metabolism: a near-infrared spectroscopy study.

    PubMed

    Sokoloff, Max D; Plegue, Melissa A; Chervin, Ronald D; Barks, John D E; Shellhaas, Renée A

    2015-07-01

    Near-infrared spectroscopy (NIRS) measures oxygen metabolism and is increasingly used for monitoring critically ill neonates. The implications of NIRS-recorded data in this population are poorly understood. We evaluated NIRS monitoring for neonates with seizures. In neonates monitored with video-electroencephalography, NIRS-measured cerebral regional oxygen saturation (rSO2) and systemic O2 saturation were recorded every 5 s. Mean rSO2 was extracted for 1-h blocks before, during, and after phenobarbital doses. For each electrographic seizure, mean rSO2 was extracted for a period of three times the duration of the seizure before and after the ictal pattern, as well as during the seizure. Linear mixed models were developed to assess the impact of phenobarbital administration and of seizures on rSO2 and fractional tissue oxygen extraction. For 20 neonates (estimated gestational age: 39.6 ± 1.5 wk), 61 phenobarbital doses and 40 seizures were analyzed. Cerebral rSO2 rose (P = 0.005), and fractional tissue oxygen extraction declined (P = 0.018) with increasing phenobarbital doses. rSO2 declined during seizures, compared with baseline and postictal phases (baseline 81.2 vs. ictal 77.7 vs. postictal 79.4; P = 0.004). Fractional tissue oxygen extraction was highest during seizures (P = 0.002). Cerebral oxygen metabolism decreases after phenobarbital administration and increases during seizures. These small, but clear, changes in cerebral oxygen metabolism merit assessment for potential clinical impact.

  19. Cerebral endothelial expression of Robo1 affects brain infiltration of polymorphonuclear neutrophils during mouse stroke recovery.

    PubMed

    Gangaraju, Sandhya; Sultan, Khadeejah; Whitehead, Shawn N; Nilchi, Ladan; Slinn, Jacqueline; Li, Xuesheng; Hou, Sheng T

    2013-06-01

    Increased brain infiltration of polymorphonuclear neutrophils (PMNs) occurs early after stroke and is important in eliciting brain inflammatory response during stroke recovery. In order to understand the molecular mechanism of PMN entry, we investigated the expression and requirement for Slit1, a chemorepulsive guidance cue, and its cognate receptor, Robo1, in a long-term recovery mouse model of cerebral ischemia. The expression levels of Robo1 were significantly decreased bilaterally at 24h following reperfusion. Robo1 expression levels remained suppressed in the ipsilateral cortex until 28d post MCAO-reperfusion, while the levels of Robo1 in the contralateral cortex recovered to the level of sham-operated mouse by 7d reperfusion. Circulating PMNs express high levels of Slit1, but not Robo1. Influx of PMNs into the ischemic core area occurred early (24h) after cerebral ischemia, when endothelial Robo1 expression was significantly reduced in the ischemic brain, indicating that Robo1 may form a repulsive barrier to PMN entry into the brain parenchyma. Indeed, blocking Slit1 on PMNs in a transwell migration assay in combination with an antibody blocking of Robo1 on human umbilical vein endothelial cells (HUVEC) significantly increased PMN transmigration during oxygen glucose deprivation, an in vitro model of ischemia. Collectively, in the normal brain, the presence of Slit1 on PMNs, and Robo1 on cerebral endothelial cells, generated a repulsive force to prevent the infiltration of PMNs into the brain. During stroke recovery, a transient reduction in Robo1 expression on the cerebral endothelial cells allowed the uncontrolled infiltration of Slit1-expressing PMNs into the brain causing inflammatory reactions.

  20. Cutaneous vasoconstriction affects near-infrared spectroscopy determined cerebral oxygen saturation during administration of norepinephrine.

    PubMed

    Sørensen, Henrik; Secher, Niels H; Siebenmann, Christoph; Nielsen, Henning B; Kohl-Bareis, Matthias; Lundby, Carsten; Rasmussen, Peter

    2012-08-01

    Perioperative optimization of spatially resolved near-infrared spectroscopy determined cerebral frontal lobe oxygenation (scO2) may reduce postoperative morbidity. Norepinephrine is routinely administered to maintain cerebral perfusion pressure and, thereby, cerebral blood flow, but norepinephrine reduces the scO2. We hypothesized that norepinephrine-induced reduction in scO2 is influenced by cutaneous vasoconstriction. Fifteen healthy male subjects (25 ± 5 yr, mean ± SD) were studied during: hyperventilation (1.5 kPa end-tidal PcO2 reduction), whole-body heating, administration of norepinephrine (0.15 μg · kg · min; with and without end-tidal carbon dioxide correction), and hypoxia (FiO2: 0.12%). Arterial (saO2), skin, and internal jugular venous oxygen saturations (sjO2) were recorded, and the average cerebral capillary oxygen saturation (scapO2) was calculated. This study indicates that scO2 is influenced by skin oxygen saturation because whole-body heating increased scO2 by 3.6% (2.1-5.1%; 95% CI) and skin oxygen saturation by 3.1% (1.3-4.9%), whereas scapO2 remained unaffected. Conversely, hyperventilation decreased scO2 by 2.1% (0.4-3.7%) and scapO2 by 5.3% (3.8-6.9%), whereas skin oxygen saturation increased 1.8% (0.5-3.1%). In response to hypoxia, scO2 (10.2%; 6.6-13.7%), scapO2 (7.9%; 6.4-9.4%), and skin oxygen saturation (8.9%; 6.3-11.6%) all decreased. With administration of norepinephrine there was a 2.2% (1.0-4.3%) decrease in skin oxygen saturation and scO2 decreased 6.2% (4.2-8.0%), with scapO2 remaining unaffected. The results confirm that spatially resolved near-infrared spectroscopy detects cerebral deoxygenation with systemic hypoxic exposure and hyperventilation. However, a commonly used vasopressor norepinephrine disturbs skin oxygen saturation to an extent that influences scO2.

  1. Use of an optical technique to evaluate the cerebral vascular effects of alcohol (A): Effects on deoxyhemoglobin (DH) and levels of reduced cytochrome oxidase (rCO)

    SciTech Connect

    Barbour, R.L.; Gebiewold, A.; Altura, B.M. )

    1992-02-26

    The dose-response effects of acute A infusion were studied to examine the suggestion that A can induce stroke-like events as a consequence of cerebral vasospasm. By employing a single sending and receiving fiber, an optical backscatter measurement was employed to monitor the levels in DH and rCO in a closed cranium preparation. Anesthetized rats were prepared by cannulating a branch of the internal carotid artery and subjected to either a bolus infusion (BI) or to a constant infusion (CI) of 5 or 10% A at various rates. Results showed that low BI doses of A typically produced a slight increase in the oxyhemoglobin signal indicating that vasodilation had probably occurred. Higher BI doses, however, produced a prompt and significant reduction in the hemoglobin signal with a rise in rCO suggesting a vasoconstrictor response leading to ischemia, followed by recovery within 3-5 min. CI of A produced a similar cerebral vascular response, in a dose-related manner, but of a more sustained nature. At 30-50% of the BI dose levels, a global blanching of the brain surface occurred; rCO levels increased by 50-90% with a corresponding decline in levels of oxyhemoglobin. Control experiments using identical volumes/flow rates of Ringers solution failed to produce any alterations in the optical spectrum. Overall, these data indicate that, depending on dose, (a) A can induce vasodilatory or vasoconstrictor effects in the intact brain; (b) the more pronounced effects involve vasospasm in the cortical microcirculation leading to global ischemia as determined by elevated levels of rCO and DH; (c) optical measurements permit direct noninvasive assessment of the cerebral vascular effects of substances of abuse.

  2. Expression of TaCYP78A3, a gene encoding cytochrome P450 CYP78A3 protein in wheat (Triticum aestivum L.), affects seed size.

    PubMed

    Ma, Meng; Wang, Qian; Li, Zhanjie; Cheng, Huihui; Li, Zhaojie; Liu, Xiangli; Song, Weining; Appels, Rudi; Zhao, Huixian

    2015-07-01

    Several studies have described quantitative trait loci (QTL) for seed size in wheat, but the relevant genes and molecular mechanisms remain largely unknown. Here we report the functional characterization of the wheat TaCYP78A3 gene and its effect on seed size. TaCYP78A3 encoded wheat cytochrome P450 CYP78A3, and was specifically expressed in wheat reproductive organs. TaCYP78A3 activity was positively correlated with the final seed size. Its silencing caused a reduction of cell number in the seed coat, resulting in an 11% decrease in wheat seed size, whereas TaCYP78A3 over-expression induced production of more cells in the seed coat, leading to an 11-48% increase in Arabidopsis seed size. In addition, the cell number in the final seed coat was determined by the TaCYP78A3 expression level, which affected the extent of integument cell proliferation in the developing ovule and seed. Unfortunately, TaCYP78A3 over-expression in Arabidopsis caused a reduced seed set due to an ovule developmental defect. Moreover, TaCYP78A3 over-expression affected embryo development by promoting embryo integument cell proliferation during seed development, which also ultimately affected the final seed size in Arabidopsis. In summary, our results indicated that TaCYP78A3 plays critical roles in influencing seed size by affecting the extent of integument cell proliferation. The present study provides direct evidence that TaCYP78A3 affects seed size in wheat, and contributes to an understanding of the cellular basis of the gene influencing seed development.

  3. Cerebral salt wasting syndrome in a patient affected of spontaneous frontoparietal subdural haematoma.

    PubMed

    Cerdá-Esteve, Mariaina; Badia, Mariona; Trujillano, Javier; Vilanova, Cecília; Maravall, Javier; Mauricio, Dídac

    2009-01-01

    Ever since cerebral salt wasting syndrome (CSW) was first described in 1950, there have been debates over its existence and whether it has an important place in the differential diagnosis of hyponatraemia. We report the case of a neurosurgical patient with sustained hyponatraemia and abnormally high sodium loss in the urine, with signs of fluid volume depletion. Hyponatraemia was not corrected after an intravenous infusion of saline solution. Stable concentrations of blood sodium above 130 mmol/l were achieved with the administration of 100 mg of hydrocortisone daily, with an ensuing reduction in sodium elimination through the urine.

  4. Autoantibodies against Cytochrome P450 Side-Chain Cleavage Enzyme in Dogs (Canis lupus familiaris) Affected with Hypoadrenocorticism (Addison's Disease).

    PubMed

    Boag, Alisdair M; Christie, Michael R; McLaughlin, Kerry A; Syme, Harriet M; Graham, Peter; Catchpole, Brian

    2015-01-01

    Canine hypoadrenocorticism likely arises from immune-mediated destruction of adrenocortical tissue, leading to glucocorticoid and mineralocorticoid deficiency. In humans with autoimmune Addison's disease (AAD) or autoimmune polyendocrine syndrome (APS), circulating autoantibodies have been demonstrated against enzymes associated with adrenal steroid synthesis. The current study investigates autoantibodies against steroid synthesis enzymes in dogs with spontaneous hypoadrenocorticism. Coding regions of canine CYP21A2 (21-hydroxylase; 21-OH), CYP17A1 (17-hydroxylase; 17-OH), CYP11A1 (P450 side-chain cleavage enzyme; P450scc) and HSD3B2 (3β hydroxysteroid dehydrogenase; 3βHSD) were amplified, cloned and expressed as 35S-methionine radiolabelled recombinant protein. In a pilot study, serum samples from 20 dogs with hypoadrenocorticism and four unaffected control dogs were screened by radio-immunoprecipitation assay. There was no evidence of reactivity against 21-OH, 17-OH or 3βHSD, but five dogs with hypoadrenocorticism showed immunoreactivity to P450scc compared with controls. Serum samples were subsequently obtained from 213 dogs diagnosed with hypoadrenocorticism and 110 dogs from a hospital control population. Thirty control dogs were randomly selected to establish a threshold for antibody positivity (mean + 3 × standard deviation). Dogs with hypoadrenocorticism were more likely to be P450scc autoantibody positive than hospital controls (24% vs. 1.2%, respectively; p = 0.0016). Sex was significantly associated with the presence of P450scc autoantibodies in the case population, with 30% of females testing positive compared with 17% of males (p = 0.037). Significant associations with breed (p = 0.015) and DLA-type (DQA1*006:01 allele; p = 0.017) were also found. This cross-sectional study indicates that P450scc autoantibodies are present in a proportion of dogs affected with hypoadrenocorticism.

  5. Characterization of mutations in the cytochrome b subunit of the bc1 complex of Rhodobacter sphaeroides that affect the quinone reductase site (Qc).

    PubMed

    Hacker, B; Barquera, B; Crofts, A R; Gennis, R B

    1993-04-27

    The cytochrome b subunit of the bc1 complex contains two heme components, cytochrome bL and cytochrome bH, and is the locus of both a quinol oxidizing site (Qo or Qz) and a quinone reducing site (Qi or Qc). The quinone reductase site has been previously characterized as the site of interaction for a set of inhibitors including antimycin A, diuron, funiculosin, and HQNO. In this paper, four highly conserved residues in the cytochrome b subunit of Rhodobacter sphaeroides (A52, H217, K251, and D252) were targeted for site-directed mutagenesis. These residues were chosen as being likely to be at or near the quinone reductase site, on the basis of known locations of missense mutations in the homologous yeast subunit that confer resistance to Qc-directed inhibitors. The site-directed mutants all exhibit a normal rate of reduction of cytochrome bH, suggesting a fully functional quinol oxidizing site. However, each of the mutants is impaired, to varying degrees, in the rate of reoxidation of cytochrome bH. Two mutants (H217A and D252A) are unable to grow photosynthetically, indicating a severe defect in the bc1 complex. In both cases, the cause of the defect is the lack of reoxidation of cytochrome bH by ubiquinone. This is the first report of mutations that selectively impair the rate of electron transfer from cytochrome bH to the Qc-site. This set of mutations will be useful not only for modeling the structure of the quinone reducing site but also in elucidating the catalytic mechanism of this portion of the Q-cycle.

  6. The pgr1 mutation in the Rieske subunit of the cytochrome b6f complex does not affect PGR5-dependent cyclic electron transport around photosystem I.

    PubMed

    Okegawa, Yuki; Tsuyama, Michito; Kobayashi, Yoshichika; Shikanai, Toshiharu

    2005-08-05

    Although photosystem I (PSI) cyclic electron transport is essential for plants, our knowledge of the route taken by electrons is very limited. To assess whether ferredoxin (Fd) donates electrons directly to plastoquinone (PQ) or via a Q-cycle in the cytochrome (cyt) b(6)f complex in PSI cyclic electron transport, we characterized the activity of PSI cyclic electron transport in an Arabidopsis mutant, pgr1 (proton gradient regulation). In pgr1, Q-cycle activity was hypersensitive to acidification of the thylakoid lumen because of an amino acid alteration in the Rieske subunit of the cyt b(6)f complex, resulting in a conditional defect in Q-cycle activity. In vitro assays using ruptured chloroplasts did not show any difference in the activity of PGR5-dependent PQ reduction by Fd, which functions in PSI cyclic electron transport in vivo. In contrast to the pgr5 defect, the pgr1 defect did not show any synergistic effect on the quantum yield of photosystem II in crr2-2, a mutant in which NDH (NAD(P)H dehydrogenase) activity was impaired. Furthermore, the simultaneous determination of the quantum yields of both photosystems indicated that the ratio of linear and PSI cyclic electron transport was not significantly affected in pgr1. All the results indicated that the pgr1 mutation did not affect PGR5-dependent PQ reduction by Fd. The phenotypic differences between pgr1 and pgr5 indicate that maintenance of the proper balance of linear and PSI cyclic electron transport is essential for preventing over-reduction of the stroma.

  7. Robot-assisted gait training might be beneficial for more severely affected children with cerebral palsy.

    PubMed

    van Hedel, Hubertus J A; Meyer-Heim, Andreas; Rüsch-Bohtz, Christina

    2016-12-01

    Robot-assisted gait training (RAGT) can complement conventional therapies in children with cerebral palsy. We investigated changes in walking-related outcomes between children with different Gross Motor Function Classification System (GMFCS) levels and the dose-response relationship. Data from 67 children (3.9-19.9 years) with GMFCS levels II-IV were evaluated retrospectively. Every child received RAGT with the Lokomat complementing a multidisciplinary rehabilitation program. Changes in various walking-related outcomes were assessed. Walking-related outcomes did not improve differently between GMFCS level groups. Significant within-group improvements were mainly observed in children with GMFCS level IV. A dose-response relationship was present for children with GMFCS levels III and IV. Our results indicated that, although children with a GMFCS level IV walked less during an average Lokomat session, they experienced significant improvements in walking-related outcomes. Further, training dose correlated with changes in walking-related outcomes. However, between-group differences in changes in walking-related outcomes were not significant.

  8. Acute Physical Exercise Affects Cognitive Functioning in Children With Cerebral Palsy.

    PubMed

    Maltais, Désirée B; Gane, Claire; Dufour, Sophie-Krystale; Wyss, Dominik; Bouyer, Laurent J; McFadyen, Bradford J; Zabjek, Karl; Andrysek, Jan; Voisen, Julien I

    2016-05-01

    Little is known about the effects of acute exercise on the cognitive functioning of children with cerebral palsy (CP). Selected cognitive functions were thus measured using a pediatric version of the Stroop test before and after maximal, locomotor based aerobic exercise in 16 independently ambulatory children (8 children with CP), 6-15 years old. Intense exercise had: 1) a significant, large, positive effect on reaction time (RT) for the CP group (preexercise: 892 ± 56.5 ms vs. postexercise: 798 ± 45.6 ms, p < .002, d = 1.87) with a trend for a similar but smaller response for the typically developing (TD) group (preexercise: 855 ± 56.5 ms vs. postexercise: 822 ± 45.6 ms, p < .08, d = 0.59), and 2) a significant, medium, negative effect on the interference effect for the CP group (preexercise: 4.5 ± 2.5%RT vs. postexercise: 13 ± 2.9%RT, p < .04, d = 0.77) with no significant effect for the TD group (preexercise: 7.2 ± 2.5%RT vs. postexercise: 6.9 ± 2.9%RT, p > .4, d = 0.03). Response accuracy was high in both groups pre- and postexercise (>96%). In conclusion, intense exercise impacts cognitive functioning in children with CP, both by increasing processing speed and decreasing executive function.

  9. Cerebral blood volume affects blood–brain barrier integrity in an acute transient stroke model

    PubMed Central

    Huang, Shuning; Kim, Jeong Kon; Atochin, Dmitriy N; Farrar, Christian T; Huang, Paul L; Suh, Ji Yeon; Kwon, Seon Joo; Shim, Woo Hyun; Cho, Hyungjoon; Cho, Gyunggoo; Kim, Young Ro

    2013-01-01

    Insufficient vascular reserve after an ischemic stroke may induce biochemical cascades that subsequently deteriorate the blood–brain barrier (BBB) function. However, the direct relationship between poor cerebral blood volume (CBV) restoration and BBB disruption has not been examined in acute stroke. To quantify BBB integrity at acute stages of transient stroke, in particular for cases in which extravasation of the standard contrast agent (Gd-DTPA) is not observed, we adopted the water exchange index (WEI), a novel magnetic resonance image-derived parameter to estimate the water permeability across the BBB. The apparent diffusion coefficient (ADC) and R2 relaxation rate constant were also measured for outlining the tissue abnormality, while fractional CBV and WEI were quantified for assessing vascular alterations. The significantly decreased ADC and R2 in the ischemic cortices did not correlate with the changes in CBV or WEI. In contrast, a strong negative correlation between the ipsilesional WEI and CBV was found, in which stroke mice were clustered into two groups: (1) high WEI and low CBV and (2) normal WEI and CBV. The low CBV observed for mice with a disrupted BBB, characterized by a high WEI, indicates the importance of CBV restoration for maintaining BBB stability in acute stroke. PMID:23462571

  10. Effects of the lifting manipulation of scalp acupuncture for raising myodynamia of the affected limbs in hemiplegic patients due to cerebral thrombosis.

    PubMed

    Kong, Yaoqi; Xu, Fu; Lin, Xiurong; Feng, Zhengen; Shi, Hongfei; Yu, Guoqiao; Hu, Lirong; Li, Xinwei; Jiang, Lingzhen

    2005-12-01

    To provide a new therapy with definite quality controllable therapeutic effects for functional restoration of the affected limbs in hemiplegic patients due to cerebral thrombosis. 180 patients with hemiplegia due to cerebral thrombosis were randomly divided into 2 groups: the treatment group (treated with scalp acupuncture by using the lifting manipulation) and the control group (treated with scalp acupuncture by using the twirling manipulation). Evaluations were given for the two groups based on the improvement of myodynamia and comprehensive functions after the treatment. Both groups showed increased myodynamia, but with different cured and much relieved rates (86.67% in the treatment group and 5% in the control group, P<0.01). Scalp acupuncture with the lifting manipulation can dramatically increase myodynamia of the affected limbs in hemiplegic patients due to cerebral thrombosis.

  11. Toll Like Receptor 4 Affects the Cerebral Biochemical Changes Induced by MPTP Treatment.

    PubMed

    Conte, Carmela; Roscini, Luca; Sardella, Roccaldo; Mariucci, Giuseppina; Scorzoni, Stefania; Beccari, Tommaso; Corte, Laura

    2017-02-01

    The etiology and pathogenesis of Parkinson's disease (PD) are still unclear. However, multiple lines of evidence suggest a critical role of the toll like receptor 4 (TLR4) in inflammatory response and neuronal death. Neuroinflammation may be associated with the misfolding and aggregation of proteins accompanied by a change in their secondary structure. Recent findings also suggest that biochemical perturbations in cerebral lipid content could contribute to the pathogenesis of central nervous system (CNS) disorders, including PD. Thus, it is of great importance to determine the biochemical changes that occur in PD. In this respect, Fourier Transform Infrared (FTIR) spectroscopy represents a useful tool to detect molecular alterations in biological systems in response to stress stimuli. By relying upon FTIR approach, this study was designed to elucidate the potential role of TLR4 in biochemical changes induced by methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin in a mouse model of PD. The analysis of the FTIR spectra was performed in different brain regions of both wild type (WT) and toll like receptor 4-deficient (TLR4(-/-)) mice. It revealed that each brain region exhibited a characteristic molecular fingerprint at baseline, with no significant differences between genotypes. Conversely, WT and TLR4(-/-) mice showed differential biochemical response to MPTP toxicity, principally related to lipid and protein composition. These differences appeared to be characteristic for each brain area. Furthermore, the present study showed that WT mice resulted more vulnerable than TLR4(-/-) animals to striatal dopamine (DA) depletion following MPTP treatment. These results support the hypothesis of a possible involvement of TLR4 in biochemical changes occurring in neurodegeneration.

  12. Do Sustained Lung Inflations during Neonatal Resuscitation Affect Cerebral Blood Volume in Preterm Infants? A Randomized Controlled Pilot Study

    PubMed Central

    Schwaberger, Bernhard; Pichler, Gerhard; Avian, Alexander; Binder-Heschl, Corinna; Baik, Nariae; Urlesberger, Berndt

    2015-01-01

    Background Sustained lung inflations (SLI) during neonatal resuscitation may promote alveolar recruitment in preterm infants. While most of the studies focus on respiratory outcome, the impact of SLI on the brain hasn’t been investigated yet. Objective Do SLI affect cerebral blood volume (CBV) in preterm infants? Methods Preterm infants of gestation 28 weeks 0 days to 33 weeks 6 days with requirement for respiratory support (RS) were included in this randomized controlled pilot trial. Within the first 15 minutes after birth near-infrared spectroscopy (NIRS) measurements using ‘NIRO-200-NX’ (Hamamatsu, Japan) were performed to evaluate changes in CBV and cerebral tissue oxygenation. Two groups were compared based on RS: In SLI group RS was given by applying 1–3 SLI (30 cmH2O for 15 s) continued by respiratory standard care. Control group received respiratory standard care only. Results 40 infants (20 in each group) with mean gestational age of 32 weeks one day (±2 days) and birth weight of 1707 (±470) g were included. In the control group ΔCBV was significantly decreasing, whereas in SLI group ΔCBV showed similar values during the whole period of 15 minutes. Comparing both groups within the first 15 minutes ΔCBV showed a tendency toward different overall courses (p = 0.051). Conclusion This is the first study demonstrating an impact of SLI on CBV. Further studies are warranted including reconfirmation of the present findings in infants with lower gestational age. Future investigations on SLI should not only focus on respiratory outcome but also on the consequences on the developing brain. Trial Registration German Clinical Trials Register DRKS00005161 https://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_EN.do PMID:26406467

  13. Restricted Arm Swing Affects Gait Stability and Increased Walking Speed Alters Trunk Movements in Children with Cerebral Palsy.

    PubMed

    Delabastita, Tijs; Desloovere, Kaat; Meyns, Pieter

    2016-01-01

    Observational research suggests that in children with cerebral palsy, the altered arm swing is linked to instability during walking. Therefore, the current study investigates whether children with cerebral palsy use their arms more than typically developing children, to enhance gait stability. Evidence also suggests an influence of walking speed on gait stability. Moreover, previous research highlighted a link between walking speed and arm swing. Hence, the experiment aimed to explore differences between typically developing children and children with cerebral palsy taking into account the combined influence of restricting arm swing and increasing walking speed on gait stability. Spatiotemporal gait characteristics, trunk movement parameters and margins of stability were obtained using three dimensional gait analysis to assess gait stability of 26 children with cerebral palsy and 24 typically developing children. Four walking conditions were evaluated: (i) free arm swing and preferred walking speed; (ii) restricted arm swing and preferred walking speed; (iii) free arm swing and high walking speed; and (iv) restricted arm swing and high walking speed. Double support time and trunk acceleration variability increased more when arm swing was restricted in children with bilateral cerebral palsy compared to typically developing children and children with unilateral cerebral palsy. Trunk sway velocity increased more when walking speed was increased in children with unilateral cerebral palsy compared to children with bilateral cerebral palsy and typically developing children and in children with bilateral cerebral palsy compared to typically developing children. Trunk sway velocity increased more when both arm swing was restricted and walking speed was increased in children with bilateral cerebral palsy compared to typically developing children. It is proposed that facilitating arm swing during gait rehabilitation can improve gait stability and decrease trunk movements in

  14. Restricted Arm Swing Affects Gait Stability and Increased Walking Speed Alters Trunk Movements in Children with Cerebral Palsy

    PubMed Central

    Delabastita, Tijs; Desloovere, Kaat; Meyns, Pieter

    2016-01-01

    Observational research suggests that in children with cerebral palsy, the altered arm swing is linked to instability during walking. Therefore, the current study investigates whether children with cerebral palsy use their arms more than typically developing children, to enhance gait stability. Evidence also suggests an influence of walking speed on gait stability. Moreover, previous research highlighted a link between walking speed and arm swing. Hence, the experiment aimed to explore differences between typically developing children and children with cerebral palsy taking into account the combined influence of restricting arm swing and increasing walking speed on gait stability. Spatiotemporal gait characteristics, trunk movement parameters and margins of stability were obtained using three dimensional gait analysis to assess gait stability of 26 children with cerebral palsy and 24 typically developing children. Four walking conditions were evaluated: (i) free arm swing and preferred walking speed; (ii) restricted arm swing and preferred walking speed; (iii) free arm swing and high walking speed; and (iv) restricted arm swing and high walking speed. Double support time and trunk acceleration variability increased more when arm swing was restricted in children with bilateral cerebral palsy compared to typically developing children and children with unilateral cerebral palsy. Trunk sway velocity increased more when walking speed was increased in children with unilateral cerebral palsy compared to children with bilateral cerebral palsy and typically developing children and in children with bilateral cerebral palsy compared to typically developing children. Trunk sway velocity increased more when both arm swing was restricted and walking speed was increased in children with bilateral cerebral palsy compared to typically developing children. It is proposed that facilitating arm swing during gait rehabilitation can improve gait stability and decrease trunk movements in

  15. Plantarflexor training affects propulsive force generation during gait in children with spastic hemiplegic cerebral palsy: a pilot study

    PubMed Central

    Ishihara, Misako; Higuchi, Yumi; Yonetsu, Ryo; Kitajima, Hiromi

    2015-01-01

    [Purpose] The purpose of this preliminary study was to assess the trade-off relationship between the hip and ankle joints after plantarflexor training in children with spastic hemiplegic cerebral palsy (CP). [Subjects and Methods] Three boys aged 9, 10, and 13 years with spastic hemiplegic CP participated in the study. Gait analysis was performed using a three-dimensional motion analysis device and a floor reaction force detection device before and after plantarflexor training. Data on gait speed and stride length for both sides were collected. Peak hip and ankle powers in the sagittal plane and ankle-to-hip power ratio (A2/H3 ratio) were calculated. Plantarflexor training comprised heel raises and exercise band resistance at the participant’s home (3 times/week for 12 weeks). [Results] The A2/H3 ratio increased significantly on both sides in two of three subjects after training. Peak A2 power increased significantly on both sides in subject 3 and on the affected side of subject 2. Peak H3 power decreased significantly on the non-affected side of subjects 1 and 2. [Conclusion] This study confirmed that two of three subjects demonstrated a trade-off relationship between the hip and ankle joints during gait after plantarflexor training. PMID:26157201

  16. RESEARCH PAPERDrp1 is dispensable for apoptotic cytochrome c release in primed MCF10A and fibroblast cells but affects Bcl-2 antagonist-induced respiratory changes

    PubMed Central

    Clerc, P; Ge, S X; Hwang, H; Waddell, J; Roelofs, B A; Karbowski, M; Sesaki, H; Polster, B M

    2014-01-01

    BACKGROUND AND PURPOSE Dynamin-related protein 1 (Drp1) mediates mitochondrial fission and is thought to promote Bax/Bak-induced cytochrome c release during apoptosis. Conformationally active Bax, Bak and Bax/Bak-activating BH3-only proteins, such as Bim, are restrained by anti-apoptotic Bcl-2 proteins in cells that are ‘primed for death’. Inhibition of Bcl-2/Bcl-xL/Bcl-w by the antagonist ABT-737 causes rapid apoptosis of primed cells. Hence, we determined whether Drp1 is required for cytochrome c release, respiratory alterations and apoptosis of cells that are already primed for death. EXPERIMENTAL APPROACH We tested the Drp1 inhibitor mdivi-1 for inhibition of cytochrome c release in MCF10A cells primed by Bcl-2 overexpression. We measured ATP synthesis-dependent,-independent and cytochrome c-limited maximal oxygen consumption rates (OCRs) and cell death of immortalized wild-type (WT) and Drp1 knockout (KO) mouse embryonic fibroblasts (MEFs) treated with ABT-737. KEY RESULTS Mdivi-1 failed to attenuate ABT-737-induced cytochrome c release. ABT-737 decreased maximal OCR measured in the presence of uncoupler in both WT and Drp1 KO MEF, consistent with respiratory impairment due to release of cytochrome c. However, Drp1 KO MEF were slightly less sensitive to this ABT-737-induced respiratory inhibition compared with WT, and were resistant to an initial ABT-737-induced increase in ATP synthesis-independent O2 consumption. Nevertheless, caspase-dependent cell death was not reduced. Pro-apoptotic Bax was unaltered, whereas Bak was up-regulated in Drp1 KO MEF. CONCLUSIONS AND IMPLICATIONS The findings indicate that once fibroblast cells are primed for death, Drp1 is not required for apoptosis. However, Drp1 may contribute to ABT-737-induced respiratory changes and the kinetics of cytochrome c release. LINKED ARTICLES This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http

  17. Do environmental barriers affect the parent-reported quality of life of children and adolescents with cerebral palsy?

    PubMed

    Badia, Marta; Begoña Orgaz, M; Gómez-Vela, María; Verdugo, Miguel A; Ullán, Ana M; Longo, Egmar

    2016-01-01

    Physical, social, and attitudinal environment may affect the quality of life (QoL) of children and adolescents with cerebral palsy (CP). Participants in this study included parents of 206 children and adolescents with CP (55.8% males) aged 8-18 years (M=11.96, SD=3). Distribution according to the Gross Motor Function Classification System (GMFCS) was 24.3% level I, 18% level II, 18% level III, 12.6% level IV, and 27.2 level V. Environmental barriers were assessed with the Spanish version of the European Child Environment Questionnaire (ECEQ), and QoL was assessed with the KIDSCREEN parents' version. The results of the correlation analysis revealed that GMFCS level, IQ, and type of schooling are significantly correlated with QoL. Barriers were also associated with QoL. A series of hierarchical regression analyses indicated that, after controlling for the effect of child and parent's variables, barriers at home and at school significantly contribute to QoL. These findings underscore the importance of providing interventions to produce environmental changes that contribute to the improvement of QoL.

  18. A founder mutation in the Ashkenazi Jewish population affecting messenger RNA splicing of the CCM2 gene causes cerebral cavernous malformations.

    PubMed

    Gallione, Carol J; Solatycki, Ann; Awad, Issam A; Weber, James L; Marchuk, Douglas A

    2011-07-01

    Cerebral cavernous malformations can occur sporadically or are caused by mutations in one of three identified genes. Cerebral cavernous malformations often remain clinically silent until a mutation carrier suffers a stroke or seizure. Presymptomatic genetic testing has been valuable to follow and manage cerebral cavernous malformation mutation carriers. During routine diagnostic testing, we identified a two base pair change in seven unrelated people of Ashkenazi Jewish heritage. Because of the location of the variant beyond the invariant splice donor sequence, the change was reported as a variant of unknown significance. In this study, we determined whether this change was a disease-causing mutation and whether it represents a founder mutation in the Ashkenazi Jewish population. Transcripts arising from the normal and mutant alleles were examined by reverse transcription-polymerase chain reaction from affected and unaffected Ashkenazi Jewish cerebral cavernous malformation family members. A synthetic splicing system using a chimeric exon was used to visualize the effects of the change on splice donor site utilization. The two base pair change in CCM2, c.30 + 5_6delinsTT, segregated with affected status in the study families. Reverse transcription-polymerase chain reaction revealed loss of the transcript allele that was in phase with the mutation. The two base pair change, when tested in an in vitro synthetic splicing system, altered splice donor site utilization. Resequencing of the genomic region proximal and distal to the CCM2 gene mutation revealed a common single-nucleotide polymorphism haplotype in affected individuals. The two base pair change in CCM2, c.30 + 5_6delinsTT, disrupted proper splice donor utilization leading to a degraded transcript. Single nucleotide polymorphism haplotype analysis demonstrated that this mutation was due to a founder in the Ashkenazi Jewish population. These data have the potential to simplify genetic testing for cerebral

  19. Cerebral Paragonimiasis.

    PubMed

    Miyazaki, I

    1975-01-01

    The first case of cerebral paragonimiasis was reported by Otani in Japan in 1887. This was nine years after Kerbert's discovery of the fluke in the lungs of Bengal tigers and seven years after a human pulmonary infection by the fluke was demonstrated by Baelz and Manson. The first case was a 26-year-old man who had been suffering from cough and hemosputum for one year. The patient developed convulsive seizures with subsequent coma and died. The postmortem examination showed cystic lesions in the right frontal and occipital lobes. An adult fluke was found in the occipital lesion and another was seen in a gross specimen of normal brain tissue around the affected occipital lobe. Two years after Otani's discovery, at autopsy a 29-year-old man with a history of Jacksonian seizure was reported as having cerebral paragonimiasis. Some time later, however, it was confirmed that the case was actually cerebral schistosomiasis japonica. Subsequently, cases of cerebral paragonimiasis were reported. However, the majority of these cases were not confirmed histologically. It was pointed out that some of these early cases were probably not Paragonimus infection. After World War II, reviews as well as case reports were published. Recently, investigations have been reported from Korea, with a clinicla study on 62 cases of cerebral paragonimiasis seen at the Neurology Department of the National Medical Center, Seoul, between 1958 and 1964. In 1971 Higashi described a statistical study on 105 cases of cerebral paragonimiasis that had been treated surgically in Japan.

  20. Physiologic Variations in Blood Plasminogen Levels Affect Outcomes after Acute Cerebral Thromboembolism in Mice: A Pathophysiologic Role for Microvascular Thrombosis

    PubMed Central

    Singh, Satish; Houng, Aiilyan K.; Wang, Dong; Reed, Guy L.

    2016-01-01

    Summary Background and Objectives Plasminogen appears to affect brain inflammation, cell movement, fibrinolysis, neuronal excitotoxicity and cell death. However, brain tissue and circulating blood plasminogen may have different roles and, there is large individual variation in blood plasminogen levels. The aim of this study was to determine the integrated effect of blood plasminogen levels on ischemic brain injury. Methods We examined thromboembolic stroke in mice with varying, experimentally-determined, blood plasminogen levels. Ischemic brain injury, blood-brain barrier breakdown, matrix metalloproteinase-9 expression and microvascular thrombosis were determined. Results Within the range of normal variation, plasminogen levels were strongly associated with ischemic brain injury (p<0.0001); higher blood plasminogen levels had dose-related, protective effects (p<0.0001). Higher plasminogen levels were associated with increased dissolution of the middle cerebral artery thrombus (p<0.0001). Higher plasminogen levels decreased blood-brain barrier breakdown (p<0.05), matrix metalloproteinase-9 expression (p<0.01) and reduced microvascular thrombosis (p<0.0001) in the ischemic brain. In plasminogen-deficient mice, selective restoration of blood plasminogen levels reversed the harmful effects of plasminogen deficiency on ischemic brain injury. Specific inhibition of thrombin also reversed the effect of plasminogen deficiency on ischemic injury by diminishing microvascular thrombosis, blood-brain barrier breakdown and matrix metalloproteinase-9 expression. Conclusions Variation in blood plasminogen levels, within the range seen in normal individuals, had marked effects on experimental ischemic brain injury. Higher plasminogen levels protected against ischemic brain injury, decreased blood-brain barrier breakdown, matrix metalloproteinase-9 expression and microvascular thrombosis. The protective effects of blood plasminogen appear to be mediated largely through reduction

  1. Cytochromes of Aquatic Fungi

    PubMed Central

    Gleason, Frank H.; Unestam, Torgny

    1968-01-01

    The cytochrome systems of two classes of aquatic fungi, the Oomycetes and Chytridiomycetes, were studied by means of reduced-minus-oxidized difference spectra at room and at low temperature. At room temperature, all of these fungi have a c-type cytochrome with an absorption maximum at 551 mμ and a b-type cytochrome at 564 mμ. The Oomycetes have a-type cytochromes at 605 mμ, and the Chytridiomycetes have a-type cytochromes at 606 mμ (Blastocladiales) or at 609 mμ (Monoblepharidales). Additional b-type cytochromes are found at 557 mμ in the Oomycetes and at approximately 560 mμ in the Chytridiomycetes. The data obtained from spectra at low temperature are consistent with these conclusions. Thus, the difference spectra reveal variation between the cytochrome systems of these two classes of aquatic fungi. PMID:5650068

  2. Long-lasting neuronal loss following experimental focal cerebral ischemia is not affected by combined administration of tissue plasminogen activator and hyperbaric oxygen.

    PubMed

    Hobohm, Carsten; Laignel, Félix; Kacza, Johannes; Küppers-Tiedt, Lea; Heindl, Marita; Schneider, Dietmar; Grosche, Jens; Härtig, Wolfgang; Michalski, Dominik

    2011-10-12

    Acute focal cerebral ischemia and consecutive energy failure are accompanied by neuronal death in regions with impaired cerebral blood flow. Several translational attempts of potential neuroprotective agents have failed, hence extended perspectives are required regarding the regional differences of neuronal impairment and glial involvement by using clinically relevant stroke models. This study aimed on neuronal loss following experimental focal cerebral ischemia, considering tissue plasminogen activator (tPA) as established treatment in stroke and hyperbaric oxygenation (HBO) as potential neuroprotective co-treatment. Wistar rats were subjected to embolic middle cerebral artery occlusion and underwent either treatment with tPA only, combined tPA+HBO, or no treatment. Neuronal impairment was assessed by Neuronal Nuclei (NeuN) staining in 4 ischemia-related areas and at 4 different time points after stroke induction (24hours, 7, 14 and 28 days). Additionally, spatial relationships between neuronal loss and gliosis were revealed by triple fluorescence staining of neurons, astrocytes and microglia, comparing the ipsi- and contra-lesional hemisphere. Analyzing the ischemic injury in general, a shell-like distribution of neuronal damage was observed, starting in the ischemic core and diminishing over the general ischemic area to the ischemic border zone and the primary non-affected area. This pattern remained detectable up to 4weeks after ischemia induction. Surprisingly, tPA and tPA+HBO did not markedly affect the post-ischemic course of neuronal impairment. Further studies are needed to investigate the effects of treatment with tPA or potential neuroprotective agents on neuronal integrity, with emphasis on the separation of intact neurons from those undergoing apoptosis or necrosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Impairment Severity Selectively Affects the Control of Proximal and Distal Components of Reaching Movements in Children with Hemiplegic Cerebral Palsy

    ERIC Educational Resources Information Center

    Domellof, Erik; Rosblad, Birgit; Ronnqvist, Louise

    2009-01-01

    This study explored proximal-to-distal components during goal-directed reaching movements in children with mild or moderate hemiplegic cerebral palsy (HCP); [seven females, four males; mean age 8y 6mo; SD 27mo], compared with age-matched, typically developing children (seven females, five males; mean age 8y 3mo [SD 25mo]. Severity of HCP was…

  4. Photothrombosis-induced infarction of the mouse cerebral cortex is not affected by the Nrf2-activator sulforaphane.

    PubMed

    Porritt, Michelle J; Andersson, Helene C; Hou, Linda; Nilsson, Åsa; Pekna, Marcela; Pekny, Milos; Nilsson, Michael

    2012-01-01

    Sulforaphane-induced activation of the transcription factor NF-E2 related factor 2 (Nrf2 or the gene Nfe2l2) and subsequent induction of the phase II antioxidant system has previously been shown to exert neuroprotective action in a transient model of focal cerebral ischemia. However, its ability to attenuate functional and cellular deficits after permanent focal cerebral ischemia is not clear. We assessed the neuroprotective effects of sulforaphane in the photothrombotic model of permanent focal cerebral ischemia. Sulforaphane was administered (5 or 50 mg/kg, i.p.) after ischemic onset either as a single dose or as daily doses for 3 days. Sulforaphane increased transcription of Nrf2, Hmox1, GCLC and GSTA4 mRNA in the brain confirming activation of the Nrf2 system. Single or repeated administration of sulforaphane had no effect on the infarct volume, nor did it reduce the number of activated glial cells or proliferating cells when analyzed 24 and 72 h after stroke. Motor-function as assessed by beam-walking, cylinder-test, and adhesive test, did not improve after sulforaphane treatment. The results show that sulforaphane treatment initiated after photothrombosis-induced permanent cerebral ischemia does not interfere with key cellular mechanisms underlying tissue damage.

  5. Photothrombosis-Induced Infarction of the Mouse Cerebral Cortex Is Not Affected by the Nrf2-Activator Sulforaphane

    PubMed Central

    Hou, Linda; Nilsson, Åsa; Pekna, Marcela; Pekny, Milos; Nilsson, Michael

    2012-01-01

    Sulforaphane-induced activation of the transcription factor NF-E2 related factor 2 (Nrf2 or the gene Nfe2l2) and subsequent induction of the phase II antioxidant system has previously been shown to exert neuroprotective action in a transient model of focal cerebral ischemia. However, its ability to attenuate functional and cellular deficits after permanent focal cerebral ischemia is not clear. We assessed the neuroprotective effects of sulforaphane in the photothrombotic model of permanent focal cerebral ischemia. Sulforaphane was administered (5 or 50 mg/kg, i.p.) after ischemic onset either as a single dose or as daily doses for 3 days. Sulforaphane increased transcription of Nrf2, Hmox1, GCLC and GSTA4 mRNA in the brain confirming activation of the Nrf2 system. Single or repeated administration of sulforaphane had no effect on the infarct volume, nor did it reduce the number of activated glial cells or proliferating cells when analyzed 24 and 72 h after stroke. Motor-function as assessed by beam-walking, cylinder-test, and adhesive test, did not improve after sulforaphane treatment. The results show that sulforaphane treatment initiated after photothrombosis-induced permanent cerebral ischemia does not interfere with key cellular mechanisms underlying tissue damage. PMID:22911746

  6. Dehydration affects cerebral blood flow but not its metabolic rate for oxygen during maximal exercise in trained humans.

    PubMed

    Trangmar, Steven J; Chiesa, Scott T; Stock, Christopher G; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2014-07-15

    Intense exercise is associated with a reduction in cerebral blood flow (CBF), but regulation of CBF during strenuous exercise in the heat with dehydration is unclear. We assessed internal (ICA) and common carotid artery (CCA) haemodynamics (indicative of CBF and extra-cranial blood flow), middle cerebral artery velocity (MCA Vmean), arterial-venous differences and blood temperature in 10 trained males during incremental cycling to exhaustion in the heat (35°C) in control, dehydrated and rehydrated states. Dehydration reduced body mass (75.8 ± 3 vs. 78.2 ± 3 kg), increased internal temperature (38.3 ± 0.1 vs. 36.8 ± 0.1°C), impaired exercise capacity (269 ± 11 vs. 336 ± 14 W), and lowered ICA and MCA Vmean by 12-23% without compromising CCA blood flow. During euhydrated incremental exercise on a separate day, however, exercise capacity and ICA, MCA Vmean and CCA dynamics were preserved. The fast decline in cerebral perfusion with dehydration was accompanied by increased O2 extraction (P < 0.05), resulting in a maintained cerebral metabolic rate for oxygen (CMRO2). In all conditions, reductions in ICA and MCA Vmean were associated with declining cerebral vascular conductance, increasing jugular venous noradrenaline, and falling arterial carbon dioxide tension (P aCO 2) (R(2) ≥ 0.41, P ≤ 0.01) whereas CCA flow and conductance were related to elevated blood temperature. In conclusion, dehydration accelerated the decline in CBF by decreasing P aCO 2 and enhancing vasoconstrictor activity. However, the circulatory strain on the human brain during maximal exercise does not compromise CMRO2 because of compensatory increases in O2 extraction. © 2014 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

  7. Dehydration affects cerebral blood flow but not its metabolic rate for oxygen during maximal exercise in trained humans

    PubMed Central

    Trangmar, Steven J; Chiesa, Scott T; Stock, Christopher G; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2014-01-01

    Intense exercise is associated with a reduction in cerebral blood flow (CBF), but regulation of CBF during strenuous exercise in the heat with dehydration is unclear. We assessed internal (ICA) and common carotid artery (CCA) haemodynamics (indicative of CBF and extra-cranial blood flow), middle cerebral artery velocity (MCA Vmean), arterial–venous differences and blood temperature in 10 trained males during incremental cycling to exhaustion in the heat (35°C) in control, dehydrated and rehydrated states. Dehydration reduced body mass (75.8 ± 3 vs. 78.2 ± 3 kg), increased internal temperature (38.3 ± 0.1 vs. 36.8 ± 0.1°C), impaired exercise capacity (269 ± 11 vs. 336 ± 14 W), and lowered ICA and MCA Vmean by 12–23% without compromising CCA blood flow. During euhydrated incremental exercise on a separate day, however, exercise capacity and ICA, MCA Vmean and CCA dynamics were preserved. The fast decline in cerebral perfusion with dehydration was accompanied by increased O2 extraction (P < 0.05), resulting in a maintained cerebral metabolic rate for oxygen (CMRO2). In all conditions, reductions in ICA and MCA Vmean were associated with declining cerebral vascular conductance, increasing jugular venous noradrenaline, and falling arterial carbon dioxide tension () (R2 ≥ 0.41, P ≤ 0.01) whereas CCA flow and conductance were related to elevated blood temperature. In conclusion, dehydration accelerated the decline in CBF by decreasing and enhancing vasoconstrictor activity. However, the circulatory strain on the human brain during maximal exercise does not compromise CMRO2 because of compensatory increases in O2 extraction. PMID:24835170

  8. Structural features of cytochromes P450 and ligands that affect drug metabolism as revealed by X-ray crystallography and NMR.

    PubMed

    Gay, Sean C; Roberts, Arthur G; Halpert, James R

    2010-09-01

    Cytochromes P450 (P450s) play a major role in the clearance of drugs, toxins, and environmental pollutants. Additionally, metabolism by P450s can result in toxic or carcinogenic products. The metabolism of pharmaceuticals by P450s is a major concern during the design of new drug candidates. Determining the interactions between P450s and compounds of very diverse structures is complicated by the variability in P450-ligand interactions. Understanding the protein structural elements and the chemical attributes of ligands that dictate their orientation in the P450 active site will aid in the development of effective and safe therapeutic agents. The goal of this review is to describe P450-ligand interactions from two perspectives. The first is the various structural elements that microsomal P450s have at their disposal to assume the different conformations observed in X-ray crystal structures. The second is P450-ligand dynamics analyzed by NMR relaxation studies.

  9. Resting-state cerebellar-cerebral networks are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings.

    PubMed

    Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Xiao, Changqing; Zhao, Jingping

    2015-11-26

    Dysconnectivity hypothesis posits that schizophrenia is a disorder with dysconnectivity of the cortico-cerebellar-thalamic-cortical circuit (CCTCC). However, it remains unclear to the changes of the cerebral connectivity with the cerebellum in schizophrenia patients and unaffected siblings. Forty-nine patients with first-episode, drug-naive schizophrenia patients, 46 unaffected siblings of schizophrenia patients and 46 healthy controls participated in the study. Seed-based resting-state functional connectivity approach was employed to analyze the data. Compared with the controls, the patients and the siblings share increased default-mode network (DMN) seed - right Crus II connectivity. The patients have decreased right dorsal attention network (DAN) seed - bilateral cerebellum 4,5 connectivity relative to the controls. By contrast, the siblings exhibit increased FC between the right DAN seed and the right cerebellum 6 and right cerebellum 4,5 compared to the controls. No other abnormal connectivities (executive control network and salience network) are observed in the patients/siblings relative to the controls. There are no correlations between abnormal cerebellar-cerebral connectivities and clinical variables. Cerebellar-cerebral connectivity of brain networks within the cerebellum are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings. Increased DMN connectivity with the cerebellum may serve as potential endophenotype for schizophrenia.

  10. Endocrine involvement in mitochondrial encephalomyopathy with partial cytochrome c oxidase deficiency.

    PubMed Central

    Doriguzzi, C; Palmucci, L; Mongini, T; Bresolin, N; Bet, L; Comi, G; Lala, R

    1989-01-01

    A 19-year-old man born with thyroprivic hypothyroidism, due to congenital development defect, manifested hypogonadism, stunted growth, chronic progressive external ophthalmoplegia (CPEO), diffuse muscle weakness and wasting, right bundle branch block, cerebral atrophy. Muscle biopsy showed mitochondrial abnormalities. Biochemical investigations on muscle disclosed partial (50%) cytochrome c oxidase deficiency, 58% decrease of cytochrome aa3 and 41% decrease of cytochrome b. Enzyme-linked immunosorbent assay showed decrease of the immunologically active enzyme protein. Images PMID:2540284

  11. Structural Features of Cytochromes P450 and Ligands that Affect Drug Metabolism as Revealed by X-ray Crystallography and NMR

    PubMed Central

    Gay, Sean C.; Roberts, Arthur G.; Halpert, James R.

    2010-01-01

    SUMMARY Cytochromes P450 (P450s) play a major role in the clearance of drugs, toxins, and environmental pollutants. Additionally, metabolism by P450s can result in toxic or carcinogenic products. The metabolism of pharmaceuticals by P450s is a major concern during the design of new drug candidates. Determining the interactions between P450s and compounds of very diverse structures is complicated by the variability in P450-ligand interactions. Understanding the protein structural elements and the chemical attributes of ligands that dictate their orientation in the P450 active site will aid in the development of effective and safe therapeutic agents. The goal of this review is to describe P450-ligand interactions from two perspectives. The first is the various structural elements that microsomal P450s have at their disposal to assume the different conformations observed in X-ray crystal structures. The second is P450-ligand dynamics analyzed by NMR relaxation studies. PMID:21103389

  12. Hepatic cytochrome P450 and UDP-glucuronosyl transferase are affected by five sources of dietary fiber in germ-free rats.

    PubMed

    Nugon-Baudon, L; Roland, N; Flinois, J P; Beaune, P

    1996-02-01

    The influence of dietary fiber on xenobiotic-metabolizing enzymes (XME) was assessed using germ-free rats fed inulin and other sources of fiber (wheat bran, carrot, cocoa and oat). The consumption of cocoa fiber greatly modified the hepatic cytochrome P450 isoenzymatic profile, causing a strong enhancement of 1A2 and 2B1/B2 forms, concomitant with a significant decrease of the constitutive form 2C11, compared with all of the other types of fiber. Moreover, rats fed the cocoa fiber diet had a higher specific activity of hepatic UDP-glucuronosyl transferase than their carrot fiber- and wheat bran-fed counterparts. Intestinal UDP-glucuronosyl transferase was unaffected by the type of ingested fiber. Diet composition also did not alter the specific activity of glutathione-S-transferase in the liver, small intestine, or colon. Using earlier results obtained in heteroxenic rats, we show that intestinal microflora plays a key role in some of the effects of fiber on XME, although this is not a necessary prerequisite for all of the liver alterations.

  13. Filaria martis Gmelin 1790 (Spirurida, Filariidae) affecting beech marten (Martes foina): morphological description and molecular characterisation of the cytochrome oxidase c subunit I.

    PubMed

    Otranto, Domenico; Lia, Riccardo Paolo; Cantacessi, Cinzia; Brianti, Emanuele; Traversa, Donato; Giannetto, Salvatore

    2007-09-01

    Filaria martis causes a poorly known subcutaneous filariosis in mustelids. Few information is available about lesions that F. martis causes in beech martens, on its morphology, biology and the occurrence of the infection. From 1997 to 2006, 29 beech martens from two sites of southern Italy (Sites A and B) have been necropsied. Ectoparasites and nematodes were collected and morphologically identified. A variable region of the cytochrome c oxidase subunit 1 (cox1) of F. martis has been characterised to compare females presenting caudal tips smooth without spines (i.e. Morphotype 1-Mrph. 1) and with spines (i.e. Mrph. 2). All ticks collected were identified as Haemaphysalis erinacei. Eleven animals from Site A were found infected by F. martis nematodes in subcutaneous tissue in both membranous capsules or free under the inner skin surface. The most important morphological characters of F. martis have been reported and discussed. The molecular analysis showed 100% homology among cox1 sequences from Mrph. 1 and 2 thus indicating that the shape of female posterior edge may vary among specimens of F. martis. The results here presented provide new insights into the biology, ecology and morphological characteristics of this scantly known nematode.

  14. [Long QT and torsade de pointes in a patient with acquired human immunodeficiency virus infection in multitherapy with drugs affecting cytochrome P450].

    PubMed

    Hrovatin, Enzo; Zardo, Fabio; Brieda, Marco; Dametto, Ermanno; Piazza, Rita; Antonini-Canterin, Francesco; Cassin, Matteo; Meneguzzo, Nereo; Viel, Elda; Lestuzzi, Chiara; Di Gennaro, Gianpiero; Nicolosi, Gian Luigi

    2004-09-01

    In acquired human immunodeficiency virus (HIV) infection, a long depolarization period at ECG may be the consequence of cardiac complications due to viral myocarditis or cardiomyopathy or indirectly due to autonomic neuropathy, or sometimes resulting from pharmacological treatments. Several drugs administered for direct treatment of HIV disease or its complications, such as antiretrovirus, fluconazole, and antibiotics, may induce ventricular arrhythmias due to long QT prolonged depolarization period. Also methadone, frequently associated with HIV therapy to treat patients with opiate addiction, is described in the literature to have cardiac inotropic effects. It has also the potential to increase the QT period and to develop ventricular torsade de pointes, primarily through interference with the rapid component of the delayed rectifier potassium ion current. Moreover, the use of methadone associated with other inhibitors of cytochrome P450 might increase plasma concentrations and contribute to methadone cardiac toxicity. We report the case of an HIV patient receiving antiretroviral treatment, fluconazole and high-dose methadone, who suddenly complained of vertigo, dizziness, pre-syncope and syncope due to severe ventricular arrhythmias that disappeared after discontinuation of all treatments.

  15. Inhibition of cytochrome P450 3A by clarithromycin uniformly affects the pharmacokinetics and pharmacodynamics of oxycodone in young and elderly volunteers.

    PubMed

    Liukas, Antti; Hagelberg, Nora M; Kuusniemi, Kristiina; Neuvonen, Pertti J; Olkkola, Klaus T

    2011-06-01

    The aim of this study was to investigate the effect of the cytochrome P450 3A4 inhibitor clarithromycin on the pharmacokinetics and pharmacodynamics of oral oxycodone in young and elderly subjects. Ten young and 10 elderly healthy subjects participated in this placebo-controlled, randomized, 2-phase crossover study. Subjects took clarithromycin 500 mg or placebo twice daily for 5 days. On day 4, subjects ingested an oral dose of 10 mg oxycodone. Plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 hours, and pharmacological response for 12 hours. Clarithromycin decreased the apparent clearance of oxycodone by 53% in young and 48% in elderly subjects (P < 0.001) and prolonged its elimination half-life. The mean area under the plasma concentration-time curve (AUC0-∞) of oxycodone was increased by 2.0-fold (range, 1.3-fold to 2.7-fold) (P < 0.001) in young and 2.3-fold (range, 1.1-fold to 3.8-fold) (P < 0.001) in elderly subjects. The formation of noroxycodone was decreased by 74% in young and 71% in elderly subjects (P < 0.001). The ratio of AUC0-∞ of oxycodone during the clarithromycin phase compared with the one with placebo did not differ between the age groups. Clarithromycin did not alter the pharmacological response to oxycodone. Clarithromycin increased the exposure to oral oxycodone, but the magnitude of this effect was not age related. Although the pharmacological response to oxycodone was not significantly influenced by clarithromycin, dose reductions may be necessary in the most sensitive patients to avoid adverse effects when oxycodone is used concomitantly with clarithromycin.

  16. Cerebral malaria

    PubMed Central

    Newton, C.; Hien, T. T.; White, N.

    2000-01-01

    Cerebral malaria may be the most common non-traumatic encephalopathy in the world. The pathogenesis is heterogenous and the neurological complications are often part of a multisystem dysfunction. The clinical presentation and pathophysiology differs between adults and children. Recent studies have elucidated the molecular mechanisms of pathogenesis and raised possible interventions. Antimalarial drugs, however, remain the only intervention that unequivocally affects outcome, although increasing resistance to the established antimalarial drugs is of grave concern. Artemisinin derivatives have made an impact on treatment, but other drugs may be required. With appropriate antimalarial drugs, the prognosis of cerebral malaria often depends on the management of other complications—for example, renal failure and acidosis. Neurological sequelae are increasingly recognised, but further research on the pathogenesis of coma and neurological damage is required to develop other ancillary treatments.

 PMID:10990500

  17. STUDIES IN CEREBRAL METABOLISM

    PubMed Central

    Gordan, Gilbert S.; Adams, John E.; Bentinck, Richard C.; Eisenberg, Eugene; Harper, Harold; Hobson, Quentin J. G.

    1953-01-01

    In numerous clinical observations, it has been noted that steroid hormones have effects upon the central nervous system. Earlier interpretations of this relationship were largely speculative until newer methods permitted quantitation of actions of hormones and hormonal deficiencies on cerebral metabolism. The present studies indicate that certain steroids which affect behavior also influence cerebral metabolism. PMID:13019600

  18. Cerebral hemodynamics and cerebral metabolism during cold and warm stress.

    PubMed

    Doering, T J; Brix, J; Schneider, B; Rimpler, M

    1996-01-01

    The purpose of this study was to examine if local thermo-applications affect central nervous reactions. In a crossover study, six normal, healthy volunteers at first received cold packs (Cryogel, 8-12 degrees C; Pino GmbH, Hamburg, Germany) and afterwards hot packs (Parafango, 50-60 degrees C; Pino GmbH), and another six volunteers started with the hot packs and had the cold packs later; both groups administered the hot and cold packs to their thighs. Before, during, and after treatment, cerebral blood flow velocity (CBFV) in the middle cerebri-artery (MCA) was measured continuously by transcranial Doppler sonography, whereas cerebral respiratory chain enzyme cytochrome aa3 (cCytaa3) and cerebral oxygen saturation (cHbO2) were measured by transcranial near infrared spectroscopy in frontal brain tissue. Furthermore, CO2 end-tidal and arterial blood pressure (noninvasive) were also measured. Six other volunteers received only one treatment; therefore, 15 measurements with cold and 15 measurements with hot packs were performed. During application of cold packs, a decrease of cHbO2 of 10.5% (P < 0.001) and cCytaa3 of 6.7% (P < 0.001) was found, whereas the CBFV(MCA) increased significantly (3.9%; P < 0.001) between preliminary and post-stimulus periods. When cold packs were removed, a significant increase of the cHbO2 (16.9%; P < 0.001) and cCytaa3 (9.7%; P < 0.001) was measured. With these values, cHbO2 and cCytaa3 showed an overshooting counterreaction beyond the initial level. When applying the hot packs, a contrary course of the parameters was found. cCytaa3 showed a significant increase of 9.3% (P < 0.001) at the end of the stimulus phase and a decrease of 1.9% (P = 0.02) during the post-stimulus period. The correlating increase of cHbO2 was significant at 13.7% (P < 0.005). At the end of the post-stimulus phase, a significant decrease of cHbO2 at 1.9% (P = 0.004) was recorded. With Parafango applications, a significant decrease of CBFV(MCA) at 6.9% (P < 0

  19. Haplodeficiency of Cathepsin D does not affect cerebral amyloidosis and autophagy in APP/PS1 transgenic mice.

    PubMed

    Cheng, Shaowu; Wani, Willayat Y; Hottman, David A; Jeong, Angela; Cao, Dongfeng; LeBlanc, Kyle J; Saftig, Paul; Zhang, Jianhua; Li, Ling

    2017-07-01

    Autophagy and lysosomal function are important for protein homeostasis and their dysfunction have been associated with Alzheimer's disease (AD). Increased immunoreactivities of an important lysosomal protease, cathepsin D (Cat D), are evident in amyloid plaques and neurons in patients with AD. This study tests the hypothesis that deleting one allele of the cathepsin D gene (Ctsd) impacts cerebral β-amyloidosis in amyloid-β precursor protein (APP)sw/PS1dE9 (APP/PS1) double transgenic mice. Despite a significant 38% decrease in Cat D level in APP/PS1/Ctsd+/- compared with APP/PS1/Ctsd+/+ mice, no changes in steady state levels and deposition of Aβ were found in the brain. There were also no differences in APP processing, the levels of two other Aβ-degrading proteases, the levels of autophagy related protein, such as LAMP2, P62, LC3-I, LC3-II, and Beclin-1, or the markers of neuroinflammation, observed between the APP/PS1/Ctsd+/+ and APP/PS1/Ctsd+/- mice. Our findings demonstrate that in wild-type mice, Cat D protein levels are either in excess or redundant with other factors in the brain, and at least one allele of Ctsd is dispensable for cerebral β-amyloidosis and autophagy in APP/PS1 transgenic mice. © 2017 International Society for Neurochemistry.

  20. Caffeine can affect velocity in the middle cerebral artery during hyperventilation, hypoventilation, and thinking: a transcranial Doppler study.

    PubMed

    Perod, A L; Roberts, A E; McKinney, W M

    2000-01-01

    This study examined possible caffeine-mediated changes in blood flow velocity in the middle cerebral artery (VMCA) induced by tests of cerebrovascular responsiveness. Transcranial Doppler (TCD) sonography provided simultaneous bilateral VMCA measures while healthy college students hypoventilated, hyperventilated, and performed cognitive activities (short-term remembering, generating an autobiographical image, solving problems), each in 31-second tests. VMCA measures were obtained from the same persons, in separate testing sessions, when they were noncaffeinated and under two levels of caffeine: a smaller amount (from a cola, 45 mg/12 oz) and a larger amount (from coffee, 117 mg/8 oz). Compared with the no-caffeine control condition, a smaller amount of caffeine had no significant effects on global VMCA, but a larger amount suppressed VMCA by 5.8%. Time-course analyses showed that VMCA (1) followed a triphasic pattern to increase over baselines during hypoventilation regardless of caffeine condition, (2) slowed below baselines during hyperventilation (with the degree of slowing attenuated under caffeine), and (3) increased over baselines during all cognitive activities (ranges 3.8-6.9%). It is concluded that a large amount of caffeine can suppress VMCA, and this possibility should be anticipated when TCD is used to assess cerebral hemovelocity.

  1. Conditional Deletion of Cytochrome P450 Reductase in Osteoprogenitor Cells Affects Long Bone and Skull Development in Mice Recapitulating Antley-Bixler Syndrome: Role of a Redox Enzyme in Development

    PubMed Central

    Panda, Satya P.; Guntur, Anyonya R.; Polusani, Srikanth R.; Fajardo, Roberto J.; Gakunga, Peter T.; Roman, Linda J.; Masters, Bettie Sue

    2013-01-01

    NADPH-cytochrome P450 oxidoreductase (POR) is the primary electron donor for cytochromes P450, dehydrocholesterol reductase, heme oxygenase, and squalene monooxygenase. Human patients with specific mutations in POR exhibit severe developmental malformations including disordered steroidogenesis, sexual ambiguities and various bone defects, similar to those seen in patients with Antley-Bixler syndrome (ABS). To probe the role of POR during bone development, we generated a conditional knockout mouse (CKO) by cross breeding Porlox/lox and Dermo1 Cre mice. CKO mice were smaller than their littermate controls and exhibited significant craniofacial and long bone abnormalities. Differential staining of the CKO mice skull bases shows premature fusion of the sphenooccipital and basioccipital-exoccipital synchondroses. Class III malocclusion was noted in adult knockout mice with an unusual overgrowth of the lower incisors. Shorter long bones were observed along with a reduction in the bone volume fraction, measured by microCT, in the Por-deleted mice compared to age- and sex-matched littermate controls. Concerted up- or down-regulation of proteins in the FGF signaling pathway observed by immunohistochemistry in the tibia samples of CKO mice compared to wild type controls shows a decrease in the FGF signaling pathway. To our knowledge, this is the first report of a mouse model that recapitulates both skull and long bone defects upon Por deletion, offering an approach to study the sequelae of POR mutations. This unique model demonstrates that P450 metabolism in bone itself is potentially important for proper bone development, and that an apparent link exists between the POR and FGF signaling pathways, begging the question of how an oxidation-reduction flavoprotein affects developmental and cellular signaling processes. PMID:24086598

  2. Conditional deletion of cytochrome p450 reductase in osteoprogenitor cells affects long bone and skull development in mice recapitulating antley-bixler syndrome: role of a redox enzyme in development.

    PubMed

    Panda, Satya P; Guntur, Anyonya R; Polusani, Srikanth R; Fajardo, Roberto J; Gakunga, Peter T; Roman, Linda J; Masters, Bettie Sue

    2013-01-01

    NADPH-cytochrome P450 oxidoreductase (POR) is the primary electron donor for cytochromes P450, dehydrocholesterol reductase, heme oxygenase, and squalene monooxygenase. Human patients with specific mutations in POR exhibit severe developmental malformations including disordered steroidogenesis, sexual ambiguities and various bone defects, similar to those seen in patients with Antley-Bixler syndrome (ABS). To probe the role of POR during bone development, we generated a conditional knockout mouse (CKO) by cross breeding Por (lox/lox) and Dermo1 Cre mice. CKO mice were smaller than their littermate controls and exhibited significant craniofacial and long bone abnormalities. Differential staining of the CKO mice skull bases shows premature fusion of the sphenooccipital and basioccipital-exoccipital synchondroses. Class III malocclusion was noted in adult knockout mice with an unusual overgrowth of the lower incisors. Shorter long bones were observed along with a reduction in the bone volume fraction, measured by microCT, in the Por-deleted mice compared to age- and sex-matched littermate controls. Concerted up- or down-regulation of proteins in the FGF signaling pathway observed by immunohistochemistry in the tibia samples of CKO mice compared to wild type controls shows a decrease in the FGF signaling pathway. To our knowledge, this is the first report of a mouse model that recapitulates both skull and long bone defects upon Por deletion, offering an approach to study the sequelae of POR mutations. This unique model demonstrates that P450 metabolism in bone itself is potentially important for proper bone development, and that an apparent link exists between the POR and FGF signaling pathways, begging the question of how an oxidation-reduction flavoprotein affects developmental and cellular signaling processes.

  3. Evaluation of cerebral activity in the prefrontal cortex in mood [affective] disorders during animal-assisted therapy (AAT) by near-infrared spectroscopy (NIRS): a pilot study.

    PubMed

    Aoki, Jun; Iwahashi, Kazuhiko; Ishigooka, Jun; Fukamauchi, Fumihiko; Numajiri, Maki; Ohtani, Nobuyo; Ohta, Mitsuaki

    2012-09-01

    Previous studies have shown the possibility that animal-assisted therapy (AAT) is useful for promoting the recovery of a patient's psychological, social, and physiological aspect. As a pilot study, we measured the effect that AAT had on cerebral activity using near-infrared spectroscopy (NIRS), and examined whether or not NIRS be used to evaluate the effect of AAT biologically and objectively. Two patients with mood [affective] disorders and a healthy subject participated in this study. We performed two AAT and the verbal fluency task (VFT). The NIRS signal during AAT showed great [oxy-Hb] increases in most of the prefrontal cortex (PFC) in the two patients. When the NIRS pattern during AAT was compared with that during VFT, greater or lesser differences were observed between them in all subjects. The present study suggested that AAT possibly causes biological and physiological changes in the PFC, and that AAT is useful for inducing the activity of the PFC in patients with depression who have generally been said to exhibit low cerebral activity in the PFC. In addition, the possibility was also suggested that the effect of AAT can be evaluated using NIRS physiologically and objectively.

  4. Cyanide-induced cytochrome a,a3 oxidation-reduction responses in rat brain in vivo.

    PubMed Central

    Piantadosi, C A; Sylvia, A L; Jöbsis, F F

    1983-01-01

    The sensitivity of the brain to cyanide-induced histotoxic hypoxia and the protective effects of known cyanide antagonists, have been assessed in vivo by reflectance spectrophotometry. Cyanide-related changes in cytochrome a,a3 (cytochrome c oxidase) oxidation-reduction (redox) state, tissue hemoglobin saturation, and local blood volume were continuously monitored in cerebral cortex of rats. Noncumulative, dose-dependent inhibition of the in situ mitochondrial respiratory chain was evaluated directly by measuring increases in reduction levels of the terminal oxidase. These transient cytochrome a,a3 reductions were accompanied by increases in regional cerebral hemoglobin saturation and blood volume. Cytochrome redox responses were not altered either in magnitude or kinetics by hyperoxia; however, the cyanide-cytochrome dose-response curve was greatly shifted to the right by pretreatment with sodium nitrite, and the recovery rate of cytochrome a,a3 from cyanide-induced reduction was enhanced fourfold by pretreatment with sodium thiosulfate. PMID:6313756

  5. Cerebral Palsy: how the child's age and severity of impairment affect the mother's stress and coping strategies.

    PubMed

    Ribeiro, Maysa Ferreira Martins; Vandenberghe, Luc; Prudente, Cejane Oliveira Martins; Vila, Vanessa da Silva Carvalho; Porto, Celmo Celeno

    2016-10-01

    The aim of the study was to comprehend how the age group and the severity of the motor impairment of children with cerebral palsy modify the mothers' experiences of stress and to understand the coping strategies they use. A qualitative approach was used, with the method framed on Grounded Theory Analysis. Nineteen mothers of children and adolescents with different degrees of motor impairment participated in individual semi-structured interviews. A lack of support and increased time and effort invested in parenting, at the cost of other areas of life threaten participants' physical and emotional health. Mothers of children with mild impairment suffer more from the challenge of dealing with their children's emotional problems, aggression and learning difficulties. For mothers whose children have severe impairment, the major difficulties relate to coping with health complications and functional limitations. Mothers of younger children report diverse sources of stress and scarcity of resources; while mothers of adolescents have greater experience and are able to take up their life projects again. Experience, knowledge and support received are critical for adaptation.

  6. Speech problems affect more than one in two children with cerebral palsy: Swedish population-based study.

    PubMed

    Nordberg, A; Miniscalco, C; Lohmander, A; Himmelmann, K

    2013-02-01

    To describe speech ability in a population-based study of children with cerebral palsy (CP), in relation to CP subtype, motor function, cognitive level and neuroimaging findings. A retrospective chart review of 129 children (66 girls, 63 boys) with CP, born in 1999-2002, was carried out. Speech ability and background information, such as type of CP, motor function, cognitive level and neuroimaging data, were collected and analysed. Speech disorders were found in 21% of the children and were present in all types of CP. Forty-one per cent of the children with speech disorders also had mental retardation, and 42% were able to walk independently. A further 32% of the children were nonverbal, and maldevelopment and basal ganglia lesions were most common in this group. The remaining 47% had no speech disorders, and this group was most likely to display white matter lesions of immaturity. More than half of the children in this CP cohort had a speech disorder (21%) or were nonverbal (32%). Speech ability was related to the type of CP, gross motor function, the presence of mental retardation and the localization of brain maldevelopment and lesions. Neuroimaging results differed between the three speech ability groups. ©2012 The Author(s)/Acta Paediatrica ©2012 Foundation Acta Paediatrica.

  7. Humeral external rotation handling by using the Bobath concept approach affects trunk extensor muscles electromyography in children with cerebral palsy.

    PubMed

    Grazziotin Dos Santos, C; Pagnussat, Aline S; Simon, A S; Py, Rodrigo; Pinho, Alexandre Severo do; Wagner, Mário B

    2014-10-20

    This study aimed to investigate the electromyographic activity of cervical and trunk extensors muscles in children with cerebral palsy during two handlings according to the Bobath concept. A crossover trial involving 40 spastic diplegic children was conducted. Electromyography (EMG) was used to measure muscular activity at sitting position (SP), during shoulder internal rotation (IR) and shoulder external rotation (ER) handlings, which were performed using the elbow joint as key point of control. Muscle recordings were performed at the fourth cervical (C4) and at the tenth thoracic (T10) vertebral levels. The Gross Motor Function Classification System (GMFCS) was used to assess whether muscle activity would vary according to different levels of severity. Humeral ER handling induced an increase on EMG signal of trunk extensor muscles at the C4 (P=0.007) and T10 (P<0.001) vertebral levels. No significant effects were observed between SP and humeral IR handling at C4 level; However at T10 region, humeral IR handling induced an increase of EMG signal (P=0.019). Humeral ER resulted in an increase of EMG signal at both levels, suggesting increase of extensor muscle activation. Furthermore, the humeral ER handling caused different responses on EMG signal at T10 vertebra level, according to the GMFCS classification (P=0.017). In summary, an increase of EMG signal was observed during ER handling in both evaluated levels, suggesting an increase of muscle activation. These results indicate that humeral ER handling can be used for diplegic CP children rehabilitation to facilitate cervical and trunk extensor muscles activity in a GMFCS level-dependent manner.

  8. Child characteristics, caregiver characteristics, and environmental factors affecting the quality of life of caregivers of children with cerebral palsy.

    PubMed

    Tseng, Mei-Hui; Chen, Kuan-Lin; Shieh, Jeng-Yi; Lu, Lu; Huang, Chien-Yu; Simeonsson, Rune J

    2016-12-01

    The study aimed to investigate comprehensively the determinants of the quality of life (QOL) of caregivers of children with cerebral palsy (CP) based on the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY). A total of 167 children with CP (mean age 9.06 years, SD 2.61 years) and their caregivers (mean age 40.24 years, SD 5.43 years) participated in this study. The QOL of caregivers was measured with the World Health Organization Quality of Life-BREF-Taiwan version (WHOQOL-BREF-TW). The potential determinants of QOL were collected, including child characteristics, caregiver characteristics, and environmental factors from all dimensions of the ICF-CY and analysed using multiple regression models. Four multiple regression models revealed that determinants of the QOL of caregivers of children with CP was multidimensional, encompassing child characteristics (age, type of CP, fine motor impairment, other diseases, behaviour and emotions, visual impairment, hearing impairment), caregiver characteristics (general mental health, parenting stress, marital status, family coping patterns, and socio-economic status), and environmental factors (child's medication, school setting, and current rehabilitation service, caregiver's spouse's age, family life impacts, and domestic helper). Knowledge of the determinants of QOL could serve as a guide in a holistic approach to evaluation and intervention and help plan interventions targeted at these determinants to improve the QOL of caregivers of children with CP. Implications for Rehabilitation Caregivers of children with CP had lower QOL, except the environment QOL. The QOL determinants of caregivers of children with CP are multidimensional, including child characteristics, caregiver characteristics, and environmental factors. In addition to child characteristics of severity of fine motor impairments and emotional and behavioural problems, caregiver characteristics of general mental

  9. Hemispheric specialization in affective responses, cerebral dominance for language, and handedness: Lateralization of emotion, language, and dexterity.

    PubMed

    Costanzo, Elsa Yolanda; Villarreal, Mirta; Drucaroff, Lucas Javier; Ortiz-Villafañe, Manuel; Castro, Mariana Nair; Goldschmidt, Micaela; Wainsztein, Agustina Edith; Ladrón-de-Guevara, María Soledad; Romero, Carlos; Brusco, Luis Ignacio; Camprodon, Joan A; Nemeroff, Charles; Guinjoan, Salvador Martín

    2015-07-15

    Hemispheric specialization in affective responses has received little attention in the literature. This is a fundamental variable to understand circuit dynamics of networks subserving emotion. In this study we put to test a modified "valence" hypothesis of emotion processing, considering that sadness and happiness are processed by each hemisphere in relation to dominance for language and handedness. Mood induction and language activation during functional magnetic resonance imaging (fMRI) were used in 20 right-handed and 20 nonright-handed subjects, focusing on interconnected regions known to play critical roles in affective responses: subgenual cingulate cortex, amygdala, and anterior insular cortex. We observed a consistent relationship between lateralization of affective processing, motor dexterity, and language in individuals with clear right-handedness. Sadness induces a greater activation of right-hemisphere cortical structures in right-handed, left-dominant individuals, which is not evident in nonright-handed subjects who show no consistent hemispheric dominance for language. In anterior insula, right-handed individuals displayed reciprocal activation of either hemisphere depending upon mood valence, whereas amygdala activation was predominantly left-sided regardless of mood valence. Nonright-handed individuals exhibited less consistent brain lateralization of affective processing regardless of language and motor dexterity lateralization. In contrast with traditional views on emotion processing lateralization, hemispheric specialization in affective responses is not a unitary process but is specific to the brain structure being activated.

  10. Cerebral Correlates of Amygdala Responses During Non-Conscious Perception of Facial Affect in Adolescent and Pre-Adolescent Children

    PubMed Central

    Killgore, William D. S.; Yurgelun-Todd, Deborah A.

    2009-01-01

    During nonconscious perception of facial affect, healthy adults commonly activate a right-lateralized pathway comprising the superior colliculus, pulvinar, and amygdala. Whether this system is fully developed prior to adulthood is unknown. Twenty-three healthy adolescents underwent functional magnetic resonance imaging (fMRI) while viewing fearful, angry, and happy faces, backward masked by neutral faces. Left amygdala activation differed among the three affects, showing reductions to masked anger and increases to masked fear and happy faces. During masked fear, left amygdala activation correlated positively with extrastriate cortex and temporal poles and negatively with precuneus and middle cingulate gyrus. Responses of the left amygdala to masked anger correlated positively with right parahippocampal gyrus and negatively with dorsal anterior cingulate. Amygdala responses to masked happy faces were uncorrelated with other brain regions. Contrary to the right-lateralized pathway seen in adults, adolescents show evidence of a predominantly left-lateralized extrastriate pathway during masked presentations of facial affect. PMID:20200600

  11. Autoantibodies against Cytochrome P450 Side-Chain Cleavage Enzyme in Dogs (Canis lupus familiaris) Affected with Hypoadrenocorticism (Addison’s Disease)

    PubMed Central

    Boag, Alisdair M.; Christie, Michael R.; McLaughlin, Kerry A.; Syme, Harriet M.; Graham, Peter; Catchpole, Brian

    2015-01-01

    Canine hypoadrenocorticism likely arises from immune-mediated destruction of adrenocortical tissue, leading to glucocorticoid and mineralocorticoid deficiency. In humans with autoimmune Addison’s disease (AAD) or autoimmune polyendocrine syndrome (APS), circulating autoantibodies have been demonstrated against enzymes associated with adrenal steroid synthesis. The current study investigates autoantibodies against steroid synthesis enzymes in dogs with spontaneous hypoadrenocorticism. Coding regions of canine CYP21A2 (21-hydroxylase; 21-OH), CYP17A1 (17-hydroxylase; 17-OH), CYP11A1 (P450 side-chain cleavage enzyme; P450scc) and HSD3B2 (3β hydroxysteroid dehydrogenase; 3βHSD) were amplified, cloned and expressed as 35S-methionine radiolabelled recombinant protein. In a pilot study, serum samples from 20 dogs with hypoadrenocorticism and four unaffected control dogs were screened by radio-immunoprecipitation assay. There was no evidence of reactivity against 21-OH, 17-OH or 3βHSD, but five dogs with hypoadrenocorticism showed immunoreactivity to P450scc compared with controls. Serum samples were subsequently obtained from 213 dogs diagnosed with hypoadrenocorticism and 110 dogs from a hospital control population. Thirty control dogs were randomly selected to establish a threshold for antibody positivity (mean + 3 × standard deviation). Dogs with hypoadrenocorticism were more likely to be P450scc autoantibody positive than hospital controls (24% vs. 1.2%, respectively; p = 0.0016). Sex was significantly associated with the presence of P450scc autoantibodies in the case population, with 30% of females testing positive compared with 17% of males (p = 0.037). Significant associations with breed (p = 0.015) and DLA-type (DQA1*006:01 allele; p = 0.017) were also found. This cross-sectional study indicates that P450scc autoantibodies are present in a proportion of dogs affected with hypoadrenocorticism. PMID:26618927

  12. Neurovascular Specifications in the Alzheimer-Like Brain of Mice Affected by Focal Cerebral Ischemia: Implications for Future Therapies.

    PubMed

    Michalski, Dominik; Hofmann, Sarah; Pitsch, Roman; Grosche, Jens; Härtig, Wolfgang

    2017-01-01

    Alzheimer's disease (AD), the most frequent type of dementia, is a prototypical neurodegenerative disease, but shares with stroke certain common risk factors. Consequently, how vascular pathology may modulate AD pathogenesis has gained scientific attention. Therefore, aside from typical features of AD (e.g., amyloid-β, tau hyperphosphorylation, and cholinergic dysfunction), changes within the 'neurovascular unit' (NVU) are of particular interest. This study focused on cholinergic, choline acetyltransferase (ChAT)-immunopositive, and tyrosine hydroxylase (TH)-containing neurons in association with the vasculature to explore the neurovascular complex of the AD brain affected by stroke. Wild-type and triple-transgenic (3xTg) mice of different ages underwent unilateral permanent focal cerebral ischemia. Histochemical analyses comprised diverse neuronal and vascular NVU components, and markers of AD. Immunofluorescence labeling confirmed the existence of Aβ deposits and phospho-tau together with glial reactions and morphologically altered endothelia, visualized by Solanum tuberosum lectin. Twenty-four hours after ischemia induction, immunoreactivities for ChAT and TH declined in the ischemia-affected striatum and, at least in part, in the ischemic border zone and ipsilateral neocortex. Correlation analyses indicated simultaneous degeneration of neuronal and vascular components. A trend for more severe affection of ChAT was observed in younger as compared with older mice. The present findings suggest complex interactions within the NVU of the AD-like brain affected by ischemia, comprising alterations of the cholinergic system in conjunction with vascular pathology. Hence, it may be worthwhile to explore the impact of a cellular stabilization approach on vascular and glial elements in AD in terms of a potential disease-alleviating strategy.

  13. Advice on lifestyle changes (diet, red wine and physical activity) does not affect internal carotid and middle cerebral artery blood flow velocity in patients with carotid arteriosclerosis in a randomized controlled trial.

    PubMed

    Droste, Dirk W; Iliescu, Catalina; Vaillant, Michel; Gantenbein, Manon; De Bremaeker, Nancy; Lieunard, Charlotte; Velez, Telma; Meyer, Michèle; Guth, Tessy; Kuemmerle, Andrea; Chioti, Anna

    2014-01-01

    A Mediterranean diet, with and without small daily amounts of red wine, and physical activity reduce the risk of cerebrovascular disease and improve cognition. An increase in cerebral blood flow may be the underlying mechanism. Under normal conditions, cerebral blood flow velocity changes in the internal carotid arteries and in large basal cerebral arteries correlate closely with cerebral blood flow changes, as the diameter of these vessels hardly changes and only the smaller vessels downstream change their diameter. A prospective randomized controlled trial was performed in 108 patients with carotid atherosclerosis (mean age 64 years, 67% men, 66% on statin therapy). Half of them were advised to follow a polyphenol-rich modified Mediterranean diet including 1-2 tomatoes, 3-5 walnuts and a bar of dark chocolate (25 g) a day and to perform moderate physical exercise for 30 min/day (lifestyle changes). Within these two groups, half of the patients were randomized either to avoid any alcohol or to drink 100 ml of red wine (women) or 200 ml of red wine (men) daily. Bilateral middle cerebral and internal carotid blood flow velocity (peak systolic, peak end-diastolic and mean) was measured at baseline and after 4 and 20 weeks using colour-coded duplex ultrasound. Insonation depth and insonation angle were used to identically place the sample volume during follow-up investigations. A general linear model with Tukey-Kramer adjustment for multiple comparisons was used to assess the primary end points. For the analysis we used the mean values of the right and left artery. Neither lifestyle changes nor red wine had an effect on peak systolic, peak end-diastolic or mean cerebral blood flow velocity. Advice on lifestyle changes, including a modified polyphenol-rich Mediterranean diet, a glass of red wine daily and physical exercise, did not affect middle cerebral and internal carotid blood flow velocity in our patient group with carotid atherosclerosis. An increase in cerebral

  14. Cerebral Aneurysms

    MedlinePlus

    ... cerebral aneurysm may be required to restore deteriorating respiration and reduce abnormally high pressure within the brain. ... cerebral aneurysm may be required to restore deteriorating respiration and reduce abnormally high pressure within the brain. ...

  15. Corticosterone affects the differentiation of a neuronal cerebral cortex-derived cell line through modulation of the nicotinic acetylcholine receptor.

    PubMed

    Baier, C J; Franco, D L; Gallegos, C E; Mongiat, L A; Dionisio, L; Bouzat, C; Caviedes, P; Barrantes, F J

    2014-08-22

    Chronic exposure to stress hormones has an impact on brain structures relevant to cognition. Nicotinic acetylcholine receptors (AChRs) are involved in numerous cognitive processes including learning and memory formation. In order to better understand the molecular mechanisms of chronic stress-triggered mental disease, the effect of corticosterone (CORT) on the biology of AChRs was studied in the neuronal cell line CNh. We found that chronic treatment with CORT reduced the expression levels of the α7-type neuronal AChR and, to a lesser extent, of α4-AChR. CORT also delayed the acquisition of the mature cell phenotype in CNh cells. Chronic nicotine treatment affected the differentiation of CNh cells and exerted a synergistic effect with CORT, suggesting that AChR could participate in signaling pathways that control the cell cycle. Overexpression of α7-AChR-GFP abolished the CORT effects on the cell cycle and the specific α7-AChR inhibitor, methyllycaconitine, mimicked the proliferative action exerted by CORT. Whole-cell voltage-clamp recordings showed a significant decrease in nicotine-evoked currents in CORT-treated cells. Taken together, these observations indicate that AChRs, and the α7-AChR in particular, could act as modulators of the differentiation of CNh cells and that CORT could impair the acquisition of a mature phenotype by affecting the function of this AChR subtype. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Nitric oxide-sensitive guanylyl cyclase signaling affects CO2-dependent but not pressure-dependent regulation of cerebral blood flow.

    PubMed

    Jahshan, Shadi; Dayan, Lior; Jacob, Giris

    2017-06-01

    Cerebrovascular CO2 reactivity is affected by nitric oxide (NO). We tested the hypothesis that sildenafil selectively potentiates NO-cGMP signaling, which affects CO2 reactivity. Fourteen healthy males (34 ± 2 yr) were enrolled in the study. Blood pressure (BP), ECG, velocity of cerebral blood flow (CBF; measured by transcranial Doppler), and end-tidal CO2 (EtCO2) were assessed at baseline (CO2 ~39 mmHg), during hyperventilation (CO2 ~24 mmHg), during hypercapnia (CO2 ~46 mmHg), during boluses of phenylephrine (25-200 µg), and during graded head-up tilting (HUT). Measurements were repeated 1 h after 100 mg sildenafil were taken. Results showed that sildenafil did not affect resting BP, heart rate, CBF peak and mean velocities, estimated regional cerebrovascular resistance (eCVR; mean BP/mean CBF), breath/min, and EtCO2: 117 ± 2/67 ± 3 mmHg, 69 ± 3 beats/min, 84 ± 5 and 57 ± 4 cm/s, 1.56 ± 0.1 mmHg·cm(-1)·s(-1), 14 ± 0.5 breaths/min, and 39 ± 0.9 mmHg, respectively. Sildenafil increased and decreased the hypercapnia induced in CBF and eCVR, respectively. Sildenafil also attenuated the decrease in peak velocity of CBF, 25 ± 2 vs. 20 ± 2% (P < 0.05) and increased the eCVR, 2.5 ± 0.2 vs. 2 ± 0.2% (P < 0.03) during hyperventilation. Sildenafil did not affect CBF despite significant increases in the eCVRs that were elicited by phenylephrine and HUT. This investigation suggests that sildenafil, which potentiates the NO-cGMP signaling, seems to affect the cerebrovascular CO2 reactivity without affecting the static and dynamic pressure-dependent mechanisms of cerebrovascular autoregulation. Copyright © 2017 the American Physiological Society.

  17. Mitochondrial cytochrome c biogenesis: no longer an enigma

    PubMed Central

    Babbitt, Shalon E.; Sutherland, Molly C.; Francisco, Brian San; Mendez, Deanna L.; Kranz, Robert G.

    2015-01-01

    Cytochromes c and c1are heme proteins that are essential for aerobic respiration. Release of cytochrome c from mitochondria is an important signal in apoptosis initiation. Biogenesis of c-type cytochromes involves covalent attachment of heme to two cysteines (at a conserved CXXCH sequence) in the apocytochrome. Heme attachment is catalyzed in most mitochondria by holocytochrome c synthase (HCCS), which is also necessary for import of apocytochrome c. Thus, HCCS affects cellular levels of cytochrome c, impacting mitochondrial physiology and cell death. Here, we review the mechanisms of HCCS function and the roles played by heme and residues in the CXXCH motif. Additionally, we consider concepts emerging within the two prokaryotic cytochrome c biogenesis pathways. PMID:26073510

  18. Mitochondrial cytochrome c oxidase deficiency.

    PubMed

    Rak, Malgorzata; Bénit, Paule; Chrétien, Dominique; Bouchereau, Juliette; Schiff, Manuel; El-Khoury, Riyad; Tzagoloff, Alexander; Rustin, Pierre

    2016-03-01

    As with other mitochondrial respiratory chain components, marked clinical and genetic heterogeneity is observed in patients with a cytochrome c oxidase deficiency. This constitutes a considerable diagnostic challenge and raises a number of puzzling questions. So far, pathological mutations have been reported in more than 30 genes, in both mitochondrial and nuclear DNA, affecting either structural subunits of the enzyme or proteins involved in its biogenesis. In this review, we discuss the possible causes of the discrepancy between the spectacular advances made in the identification of the molecular bases of cytochrome oxidase deficiency and the lack of any efficient treatment in diseases resulting from such deficiencies. This brings back many unsolved questions related to the frequent delay of clinical manifestation, variable course and severity, and tissue-involvement often associated with these diseases. In this context, we stress the importance of studying different models of these diseases, but also discuss the limitations encountered in most available disease models. In the future, with the possible exception of replacement therapy using genes, cells or organs, a better understanding of underlying mechanism(s) of these mitochondrial diseases is presumably required to develop efficient therapy. © 2016 Authors; published by Portland Press Limited.

  19. Mitochondrial Cytochrome c Oxidase Deficiency

    PubMed Central

    Rak, Malgorzata; Bénit, Paule; Chrétien, Dominique; Bouchereau, Juliette; Schiff, Manuel; El-Khoury, Riyad; Tzagoloff, Alexander; Rustin, Pierre

    2016-01-01

    As with other mitochondrial respiratory chain components, marked clinical and genetic heterogeneity is observed in patients with a cytochrome c oxidase deficiency. This constitutes a considerable diagnostic challenge and raises a number of puzzling questions. So far, pathological mutations have been reported in more than 30 genes, in both mitochondrial and nuclear DNA, affecting either structural subunits of the enzyme or proteins involved in its biogenesis. In this review, we discuss the possible causes of the discrepancy between the spectacular advances made in the identification of the molecular bases of cytochrome oxidase deficiency and the lack of any efficient treatment in diseases resulting from such deficiencies. This brings back many unsolved questions related to the frequent delay of clinical manifestation, variable course and severity, and tissue-involvement often associated with these diseases. In this context, we stress the importance to study different models of these diseases, but also discuss the limitations encountered in most available disease models. In the future, with the possible exception of replacement therapy using genes, cells or organs, a better understanding of underlying mechanism(s) of these mitochondrial diseases is presumably required to develop efficient therapy. PMID:26846578

  20. Cerebral Palsy (For Teens)

    MedlinePlus

    ... brain is affected and which parts of the body that section of the brain controls. If CP affects both arms and both legs, ... the case of spastic CP) or to help control seizures. And some might have special surgeries to keep their arms or legs straighter and more ... Coping With Cerebral Palsy Puberty can ...

  1. Strain on the gastrocnemii and hamstrings affecting standing balance on an inclined plane in spastic cerebral palsy. A study using a geometric model.

    PubMed

    Suzuki, N; Mita, K; Watakabe, M; Akataki, K; Okagawa, T; Kimizuka, M

    1998-01-01

    The purpose of this study was to use an non-invasive method to determine whether strain on the gastrocnemii and hamstrings influences postural balance in spastic cerebral palsy (CP). Changes in alignment during standing posture with subjects positioned on a platform that was gradually inclined were measured in 10 normal children and 11 children with CP. The changes in postural alignment were plotted and geometric models used to determine the lines where the gastrocnemii and hamstrings were maximally stretched. In this way the relationship between postural alignment and the amount of strain on the gastrocnemii and hamstrings was investigated. On the inclined platform, which caused ankle joints to become dorsiflexed as the inclination angle increased, the gastrocnemii began to be strained and the hip joints began to be flexed (trunk bent forward) at the same time. In the children with CP, the gastrocnemii were more strained by smaller degrees of inclination. Furthermore, there was one child with CP whose hamstrings were also strained on the inclined platform. We confirmed that postural balance was affected by strain on the gastrocnemii and hamstrings.

  2. Cytochrome c: functions beyond respiration.

    PubMed

    Ow, Yong-Ling P; Green, Douglas R; Hao, Zhenyue; Mak, Tak W

    2008-07-01

    Cytochrome c is primarily known for its function in the mitochondria as a key participant in the life-supporting function of ATP synthesis. However, when a cell receives an apoptotic stimulus, cytochrome c is released into the cytosol and triggers programmed cell death through apoptosis. The release of cytochrome c and cytochrome-c-mediated apoptosis are controlled by multiple layers of regulation, the most prominent players being members of the B-cell lymphoma protein-2 (BCL2) family. As well as its role in canonical intrinsic apoptosis, cytochrome c amplifies signals that are generated by other apoptotic pathways and participates in certain non-apoptotic functions.

  3. The “black evil” affecting patients with diabetes: a case of rhino orbito cerebral mucormycosis causing Garcin syndrome

    PubMed Central

    Narayanan, Santhosh; Panarkandy, Geetha; Subramaniam, Gomathy; Radhakrishnan, Chandni; Thulaseedharan, NK; Manikath, Neeraj; Ramaswamy, Sreejith; Radhakrishnan, Suma; Ekkalayil, Danish

    2017-01-01

    Mucormycosis is a life-threatening infection affecting patients with diabetes. It is an angioinvasive disease often resistant to treatment with a debilitating course and high mortality. Here, we report a case of a 45 year old woman with type 2 diabetes mellitus who presented to us with history of right-sided ptosis and facial palsy, and subsequently developed loss of vision and palatal palsy. She was in diabetic ketoacidosis. Nervous system examination revealed involvement of right second, third, fourth, sixth, seventh, ninth, and tenth cranial nerves, suggestive of Garcin syndrome. The hard palate had been eroded with formation of black eschar. Computed tomography of paranasal sinuses revealed right maxillary and ethmoid sinusitis, with spread of inflammation to infratemporal fossa and parapharynygeal neck spaces. Debridement of sinus mucosa was done, and culture of the same yielded growth of rhizopus species. Histopathological examination of the tissue showed angioinvasion and fungal hyphae suggestive of mucormycosis. She was treated with amphotericin B, posaconazole, and periodic nasal sinus debridement, but her general condition worsened after 8 weeks due to secondary sepsis and she succumbed to death. PMID:28405168

  4. Effect of ligands on cytochrome d from Azotobacter vinelandii

    SciTech Connect

    Kauffman, H.F.; van Gelder, B.F.; DerVartanian, D.V.

    1980-08-01

    Spectra of oxidized and reduced cytochrome d in particles of A. vinelandii were studied in the presence of the ligands CO, azide, and NH2OH under oxidizing, reducing, and turnover conditions. Under oxidizing conditions, spectral changes were observed on oxidized cytochrome d in the presence of CO and NH2OH showing a shift of the maximum to shorter wavelengths. Under reducing conditions, spectral changes were observed on reduced cytochrome d in the presence of CO, NO, NO2-, and NH2OH. Under turnover conditions CO, NH2OH, and azide cause a spectral shift of the absorption maximum of cytochrome d. The spectral changes caused by CO and NH2OH were interpreted as a binding of the ligands to cytochrome d changing its conformation from the oxidized state absorbing at 648 nm into a more stable liganded form. Since azide does not affect the spectral bands of oxidized and reduced cytochrome d, the spectral change during turnover in the presence of azide were ascribed to a preferential binding of azide to enzymically active conformation of cytochrome d (cytochrome dx).

  5. Water immersion to the femur level affects cerebral cortical activity in humans: functional near-infrared spectroscopy study.

    PubMed

    Sato, Daisuke; Onishi, Hideaki; Yamashiro, Koya; Iwabe, Tatsuya; Shimoyama, Yoshimitsu; Maruyama, Atsuo

    2012-04-01

    Water immersion is widely used in physiotherapy and may even improve the functional outcomes of hemiplegic patients after stroke. To investigate the cortical responses to water immersion, functional near-infrared spectroscopy (fNIRS) was used to measure cortical activations in the primary somatosensory area (S1), parietal association area (PAA), supplementary motor area (SMA), and primary motor area (M1). Nine healthy adult males were rested in a sitting position for 15 min with simultaneous measurements of fNIRS, blood pressure, and skin temperature. The fNIRS signal and other physiological parameters were measured under three conditions, the non-immersed condition (baseline control), as the immersion tank was filling with water (pouring water condition), and during sustained water immersion. Each condition lasted for 5 min. The water level was allowed to reach the femur, and during the experiment, room and water temperatures were maintained at 34°C. Oxygenated hemoglobin (oxyHb) concentrations in the S1, PAA, SMA, and M1 remained stable during baseline recording but gradually increased during water pouring and immersion. Significantly higher oxyHb levels were observed in S1 at 20 s after the onset of water immersion condition and in the PAA at 40 s. Subsequently, oxyHb levels in the SMA and M1 increased significantly 100 s after the onset of water immersion condition. In contrast, no significant changes in blood pressure, heart rate, or skin temperature were observed. Water immersion resulted in increased activity in both sensory and motor areas of cortex as measured by non-invasive fNIRS. Water immersion may enhance the efficacy of physical therapy by providing background activation to affected areas of the cortex, thereby enhancing signal processing and learning.

  6. Cerebral oxygenation during cardiopulmonary bypass

    PubMed Central

    Wardle, S; Yoxall, C; Weindling, A

    1998-01-01

    Cerebral fractional oxygen extraction (FOE) was monitored in 30 children, using near infrared spectroscopy during cardiopulmonary bypass, to investigate the effect of hypothermia and circulatory arrest. One group of children (n = 15) underwent profound hypothermia with total circulatory arrest (n = 8) or continuous flow (n =7). Another group (n = 15), of whom only one had circulatory arrest, underwent mild (n = 6) or moderate (n = 9) hypothermia.
 The mean FOE (SD) before bypass was 0.35 (0.12) and this correlated negatively with the preoperative arterial oxygen content (r=−0.58). Between the stage of cooling on bypass and cold bypass there was a reduction in FOE in all groups. Between cold bypass and rewarming there was an increase in FOE only in the groups with continuous flow. In the circulatory arrest group, the FOE remained low during rewarming and was significantly lower than that of the continuous flow group. No patients died and none had neurological abnormalities postoperatively.
 Apparent changes in oxidised cytochrome oxidase concentration were also monitored using near infrared spectroscopy. There was a fall in cytochrome aa3 on starting cardiopulmonary bypass, but there were no significant differences in the changes in cytochrome aa3 between any stage in any of the patient groups.
 Using this non-invasive technique, cooling was shown to reduce cerebral FOE. During rewarming on bypass there was an increase in cerebral FOE only in patients who had had continuous flow bypass. In contrast, the cerebral FOE in those with circulatory arrest remained constant after arrest and during the duration of the study. This may have implications for the timing of hypoxic brain injury.

 PMID:9534672

  7. Simulation of multihaem cytochromes.

    PubMed

    Soares, Cláudio M; Baptista, António M

    2012-03-09

    This article presents an overview of the simulation studies of the behaviour of multihaem cytochromes using theoretical/computational methodologies, with an emphasis on cytochrome c(3). It starts with the first studies using rigid molecules and continuum electrostatic models, where protonation and redox events were treated as independent. The gradual addition of physical details is then described, from the inclusion of proton isomerism, to the proper treatment of the thermodynamics of electron-proton coupling, to the explicit inclusion of the solvent and protein structural reorganization into the models, culminating with the method for molecular dynamics simulations at constant pH and reduction potential, where the solvation, conformational, protonation and redox features are all simulated in a fully integrated and coupled way. We end with a discussion of the strategies used to study the interaction between multihaem cytochromes, taking into account the further coupling effect introduced by the molecular association. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Effect of ligands on cytochrome d from Azotobacter vinelandii

    SciTech Connect

    Kauffman, H.F.; van Gelder, B.F.; DerVartanian, D.V.

    1980-08-01

    Spectra of oxidized and reduced cytochrome d in particles of A. vinelandii were studied in the presence of the ligands CO, azide, and NH/sub 2/OH under oxidizing, reducing, and turnover conditions. Under oxidizing conditions, spectral changes were observed on oxidized cytochrome d (absorption maximum at 648 nm) in the presence of CO and NH/sub 2/OH showing a shift of the maximum to shorter wavelengths (639 and 645 nm, respectively) and a broadening of the half-band width. Under reducing conditions, spectral changes were observed on reduced cytochrome d (absorption maximum at 631 nm) in the presence of CO (absorption maximum at 636 nm), NO, NO/sub 2/-, and NH/sub 2/OH (absorption maximum at 642 nm in the presence of dithionite). The spectral changes of cytochrome d in the presence of NH/sub 2/OH or with dithionite and NO/sub 2/- were ascribed to the formation of the NO-cytochrome d compound. Under turnover conditions CO, NH/sub 2/OH, and azide cause a spectral shift of the absorption maximum of cytochrome d from 648 nm to 636, 645, and 655 nm, respectively. With NH/sub 2/OH and azide a broadening of the half-band width of 7 and 6 nm, respectively, was also observed. The spectral changes caused by CO and NH/sub 2/OH were interpreted as a binding of the ligands to cytochrome d changing its conformation from the oxidized state absorbing at 648 nm into a more stable liganded form. Since azide does not affect the spectral bands of oxidized and reduced cytochrome d, the spectral change during turnover in the presence of azide were ascribed to a preferential binding of azide to enzymically active conformation of cytochrome d (cytochrome dx).

  9. Reversible cerebral vasoconstriction syndrome in the context of recent cerebral venous thrombosis: Report of a case.

    PubMed

    Bourvis, Nadège; Franc, Julie; Szatmary, Zoltan; Chabriat, Hugues; Crassard, Isabelle; Ducros, Anne

    2016-01-01

    Reversible cerebral constriction syndrome and cerebral venous thrombosis are two rare conditions. Reversible cerebral constriction syndrome affects the cerebral arteries and the pathology is still largely unknown. To date, no physiological link with cerebral venous thrombosis has been reported. We report here the case of a 24-year-old woman who presented a reversible cerebral constriction syndrome in the setting of a cerebral venous thrombosis. Cerebral venous thrombosis had developed in her left lateral venous sinus, within the stent placed one year before, in order to treat an idiopathic intracranial hypertension. The co-occurrence of cerebral venous thrombosis and reversible cerebral constriction syndrome in the same patient raises the issue of a potential link between them. We discuss the potential common trigger factors in this case: recent hormonal therapy; intracranial hypotension iatrogenically induced by lumbar puncture. © International Headache Society 2015.

  10. Ketoconazole inhibition of the bifunctional cytochrome P450c17 does not affect androgen formation from the endogenous lyase substrate. The catalytic site remains refractory in the course of intermediary hydroxyprogesterone processing.

    PubMed

    Kühn-Velten, W N; Lessmann, M

    1992-12-15

    The inhibition of the bifunctional steroidogenic cytochrome P450c17 (CYP17: steroid-17 alpha-hydroxylase/steroid-17,20-lyase) by the imidazole-type fungicide, [(+/-)-cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl- methyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine) (ketoconazole), was investigated with the aim of differentiating between effects on androgen formation from exogenously added and endogenously produced 17 alpha-hydroxyprogesterone. Using microsomal membranes from rat testis, turnover of progesterone by P450c17 was competitively inhibited by ketoconazole with KI = 0.40 microM. Ketoconazole did not affect the linear relationship between the ratio of productive events (corresponding to androgen formation rates) versus abortive events (corresponding to 17 alpha-hydroxyprogesterone formation rates) and the sum of catalytic events. This was an indication that this inhibitor did not interfere with intermediate processing by P450c17. Androgen formation from exogenous but not from endogenous 17 alpha-hydroxyprogesterone was competitively inhibited by ketoconazole. The simultaneous conversion of 1 microM each of [3H]progesterone and 17 alpha-hydroxy[14C]progesterone was also reduced by ketoconazole. Calculation of 3H/14C ratios in the 17 alpha-hydroxyprogesterone and androgen fractions revealed that the endogenous 17 alpha-hydroxyprogesterone pool was metabolized to androgens at rates 6.4, 11.6, 17.6 and 21.2-fold faster than the exogenous pool in the presence of 0.5, 1, 2 and 4 microM ketoconazole, respectively; this value was only 4.0 in controls. It is concluded that ketoconazole inhibits turnover of steroid ligands only when they approach the P450c17 active site in a substrate-state and that inhibition of androgen formation from progesterone is due to inhibition of the first catalytic step only. A model is described in which the P450c17 active site is refractory towards ketoconazole when the intermediary steroid is retained and being

  11. The mechanism by which oxygen and cytochrome c increase the rate of electron transfer from cytochrome a to cytochrome a3 of cytochrome c oxidase.

    PubMed

    Bickar, D; Turrens, J F; Lehninger, A L

    1986-11-05

    When cytochrome c oxidase is isolated from mitochondria, the purified enzyme requires both cytochrome c and O2 to achieve its maximum rate of internal electron transfer from cytochrome a to cytochrome a3. When reductants other than cytochrome c are used, the rate of internal electron transfer is very slow. In this paper we offer an explanation for the slow reduction of cytochrome a3 when reductants other than cytochrome c are used and for the apparent allosteric effects of cytochrome c and O2. Our model is based on the conventional understanding of cytochrome oxidase mechanism (i.e. electron transfer from cytochrome a/CuA to cytochrome a3/CuB), but assumes a relatively rapid two-electron transfer between cytochrome a/CuA and cytochrome a3/CuB and a thermodynamic equilibrium in the "resting" enzyme (the enzyme as isolated) which favors reduced cytochrome a and oxidized cytochrome a3. Using the kinetic constants that are known for this reaction, we find that the activating effects of O2 and cytochrome c on the rate of electron transfer from cytochrome a to cytochrome a3 conform to the predictions of the model and so provide no evidence of any allosteric effects or control of cytochrome c oxidase by O2 or cytochrome c.

  12. Cytochrome C — EDRN Public Portal

    Cancer.gov

    CYCS, or cytochrome C, is an electron carrier protein that is an important part of the electron transport chain in mitochondria. The cytochrome C protein is a small heme protein that associates with the inner membrane of the mitochondrion where it accepts electrons from cytochrome b and transfers them to the cytochrome oxidase complex. Cytochrome C also plays a role in apoptosis.

  13. The cytochromes of Acanthamoeba castellanii.

    PubMed Central

    Edwards, S W; Chagla, A H; Griffiths, A J; Lloyd, D

    1977-01-01

    1. Low-temperature difference spectra of gradient-purified mitochondria of Acanthamoeba castellanii reveal the presence of cytochromes b-555, b-562 and c-549, with a-type cytochromes having a broad asymmetrical maximum at 602 nm; these components were also observed in specta of whole cells. 2. The a-type cytochromes are unusual in that they have split Soret absorption maxima (at 442 and 449 nm) and an uncharacteristic CO difference spectrum. 3. CO difference spectra of whole cells and 'microsomal' membranes show large amounts of cytochrome P-420 compared with cytochrome P-450. 4. Difference spectra in the presence of cyanide indicate the presence of an a-type cytochrome and two cyanide-reacting components, one of which may be cytochrome a3. 5. Whole-cell respiration in a N2/O2 (19:1) atmosphere was decreased by 50%, suggesting the presence of a low-affinity oxidase. This lowered respiration is inhibited by 50% by CO, and the inhibition is partially light-reversible; photochemical action spectra suggest that cytochrome a3 contributes to this release of inhibition. Other CO-reacting oxidases are also present. 6. The results are discussed with the view that cytochrome a3 is present in A. castellanii, but its identification in CO difference spectra is obscured by other component(s). PMID:597258

  14. Structure of the Zymomonas mobilis respiratory chain: oxygen affinity of electron transport and the role of cytochrome c peroxidase.

    PubMed

    Balodite, Elina; Strazdina, Inese; Galinina, Nina; McLean, Samantha; Rutkis, Reinis; Poole, Robert K; Kalnenieks, Uldis

    2014-09-01

    The genome of the ethanol-producing bacterium Zymomonas mobilis encodes a bd-type terminal oxidase, cytochrome bc1 complex and several c-type cytochromes, yet lacks sequences homologous to any of the known bacterial cytochrome c oxidase genes. Recently, it was suggested that a putative respiratory cytochrome c peroxidase, receiving electrons from the cytochrome bc1 complex via cytochrome c552, might function as a peroxidase and/or an alternative oxidase. The present study was designed to test this hypothesis, by construction of a cytochrome c peroxidase mutant (Zm6-perC), and comparison of its properties with those of a mutant defective in the cytochrome b subunit of the bc1 complex (Zm6-cytB). Disruption of the cytochrome c peroxidase gene (ZZ60192) caused a decrease of the membrane NADH peroxidase activity, impaired the resistance of growing culture to exogenous hydrogen peroxide and hampered aerobic growth. However, this mutation did not affect the activity or oxygen affinity of the respiratory chain, or the kinetics of cytochrome d reduction. Furthermore, the peroxide resistance and membrane NADH peroxidase activity of strain Zm6-cytB had not decreased, but both the oxygen affinity of electron transport and the kinetics of cytochrome d reduction were affected. It is therefore concluded that the cytochrome c peroxidase does not terminate the cytochrome bc1 branch of Z. mobilis, and that it is functioning as a quinol peroxidase.

  15. Cerebral malaria

    PubMed Central

    Rénia, Laurent; Wu Howland, Shanshan; Claser, Carla; Charlotte Gruner, Anne; Suwanarusk, Rossarin; Hui Teo, Teck; Russell, Bruce; Ng, Lisa

    2012-01-01

    Cerebral malaria is the most severe pathology caused by the malaria parasite, Plasmodium falciparum. The pathogenic mechanisms leading to cerebral malaria are still poorly defined as studies have been hampered by limited accessibility to human tissues. Nevertheless, histopathology of post-mortem human tissues and mouse models of cerebral malaria have indicated involvement of the blood-brain barrier in cerebral malaria. In contrast to viruses and bacteria, malaria parasites do not infiltrate and infect the brain parenchyma. Instead, rupture of the blood-brain barrier occurs and may lead to hemorrhages resulting in neurological alterations. Here, we review the most recent findings from human studies and mouse models on the interactions of malaria parasites and the blood-brain barrier, shedding light on the pathogenesis of cerebral malaria, which may provide directions for possible interventions. PMID:22460644

  16. Cytochromes P450

    PubMed Central

    Werck-Reichhart, Danièle; Bak, Søren; Paquette, Suzanne

    2002-01-01

    There are 272 cytochrome P450 genes (including 26 pseudogenes) in the Arabidopsis genome. P450s thus form one of the largest families of proteins in higher plants. This explosion of the P450 family is thought to have occurred via gene duplication and conversion, and to result from the need of sessile plants to adapt to a harsh environment and to protect themselves from pathogens and predators. P450s sometimes share less than 20% identity and catalyze extremely diverse reactions. Their biological functions range from the synthesis of structural macromolecules such as lignin, cutin or suberin, to the synthesis or catabolism of all types of hormone or signaling molecules, the synthesis of pigments and defense compounds, and to the metabolism of xenobiotics. In despite of a huge acceleration in our understanding of plant P450 functions in the recent years, the vast majority of these functions remain completely unknown. PMID:22303202

  17. Cytochromes P450

    PubMed Central

    Bak, Søren; Beisson, Fred; Bishop, Gerard; Hamberger, Björn; Höfer, René; Paquette, Suzanne; Werck-Reichhart, Danièle

    2011-01-01

    There are 244 cytochrome P450 genes (and 28 pseudogenes) in the Arabidopsis genome. P450s thus form one of the largest gene families in plants. Contrary to what was initially thought, this family diversification results in very limited functional redundancy and seems to mirror the complexity of plant metabolism. P450s sometimes share less than 20% identity and catalyze extremely diverse reactions leading to the precursors of structural macromolecules such as lignin, cutin, suberin and sporopollenin, or are involved in biosynthesis or catabolism of all hormone and signaling molecules, of pigments, odorants, flavors, antioxidants, allelochemicals and defense compounds, and in the metabolism of xenobiotics. The mechanisms of gene duplication and diversification are getting better understood and together with co-expression data provide leads to functional characterization. PMID:22303269

  18. Cerebral Palsy (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Cerebral Palsy KidsHealth > For Parents > Cerebral Palsy A A A ... kids who are living with the condition. About Cerebral Palsy Cerebral palsy is one of the most common ...

  19. Cerebral palsy - resources

    MedlinePlus

    Resources - cerebral palsy ... The following organizations are good resources for information on cerebral palsy : National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/disorders/cerebral_palsy/cerebral_palsy. ...

  20. Cerebral Palsy (For Teens)

    MedlinePlus

    ... Right Sport for You Healthy School Lunch Planner Cerebral Palsy KidsHealth > For Teens > Cerebral Palsy Print A A ... do just what everyone else does. What Is Cerebral Palsy? Cerebral palsy (CP) is a disorder of the ...

  1. Cox26 is a novel stoichiometric subunit of the yeast cytochrome c oxidase.

    PubMed

    Levchenko, Maria; Wuttke, Jan-Moritz; Römpler, Katharina; Schmidt, Bernhard; Neifer, Klaus; Juris, Lisa; Wissel, Mirjam; Rehling, Peter; Deckers, Markus

    2016-07-01

    The cytochrome c oxidase (COX) is the terminal enzyme of the respiratory chain. The complex accepts electrons from cytochrome c and passes them onto molecular oxygen. This process contributes to energy capture in the form of a membrane potential across the inner membrane. The enzyme complex assembles in a stepwise process from the three mitochondria-encoded core subunits Cox1, Cox2 and Cox3, which associate with nuclear-encoded subunits and cofactors. In the yeast Saccharomyces cerevisiae, the cytochrome c oxidase associates with the bc1-complex into supercomplexes, allowing efficient energy transduction. Here we report on Cox26 as a protein found in respiratory chain supercomplexes containing cytochrome c oxidase. Our analyses reveal Cox26 as a novel stoichiometric structural subunit of the cytochrome c oxidase. A loss of Cox26 affects cytochrome c oxidase activity and respirasome organization.

  2. Cerebral palsy.

    PubMed

    Colver, Allan; Fairhurst, Charles; Pharoah, Peter O D

    2014-04-05

    The syndrome of cerebral palsy encompasses a large group of childhood movement and posture disorders. Severity, patterns of motor involvement, and associated impairments such as those of communication, intellectual ability, and epilepsy vary widely. Overall prevalence has remained stable in the past 40 years at 2-3·5 cases per 1000 livebirths, despite changes in antenatal and perinatal care. The few studies available from developing countries suggest prevalence of comparable magnitude. Cerebral palsy is a lifelong disorder; approaches to intervention, whether at an individual or environmental level, should recognise that quality of life and social participation throughout life are what individuals with cerebral palsy seek, not improved physical function for its own sake. In the past few years, the cerebral palsy community has learned that the evidence of benefit for the numerous drugs, surgery, and therapies used over previous decades is weak. Improved understanding of the role of multiple gestation in pathogenesis, of gene environment interaction, and how to influence brain plasticity could yield significant advances in treatment of the disorder. Reduction in the prevalence of post-neonatal cerebral palsy, especially in developing countries, should be possible through improved nutrition, infection control, and accident prevention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. The cytochrome p450 homepage.

    PubMed

    Nelson, David R

    2009-10-01

    The Cytochrome P450 Homepage is a universal resource for nomenclature and sequence information on cytochrome P450 ( CYP ) genes. The site has been in continuous operation since February 1995. Currently, naming information for 11,512 CYPs are available on the web pages. The P450 sequences are manually curated by David Nelson, and the nomenclature system conforms to an evolutionary scheme such that members of CYP families and subfamilies share common ancestors. The organisation and content of the Homepage are described.

  4. Reversible cerebral vasoconstriction syndrome.

    PubMed

    Ducros, Anne

    2014-01-01

    Reversible cerebral vasoconstriction syndrome is characterized by severe headaches with or without focal neurologic deficits and/or seizures, and segmental constriction of cerebral arteries that resolves within 3 months. This increasingly recognized syndrome is supposedly due to a transient disturbance in the control of cerebral vascular tone with sympathetic overactivity. It can cause stroke in the young. It affects mainly middle-aged women. More than half the cases occur after exposure to vasoactive substances or during postpartum. The manifestations have a monophasic course, without new clinical symptom after 4 weeks, and range from pure cephalalgic forms with recurrent thunderclap headaches over 1-2 weeks to rare catastrophic forms with multiple hemorrhagic and ischemic strokes, brain edema and death. Diagnosis may be hampered by the dynamic nature of clinicoradiological features. Convexity subarachnoid hemorrhage or stroke may occur a few days after initial normal imaging, and cerebral vasoconstriction is maximal on angiography 2-3 weeks after clinical onset. Symptomatic treatment includes rest and removal of vasoactive substances. Nimodipine has been proposed to reduce thunderclap headaches within 48 hours, but has no proven effect on the hemorrhagic and ischemic complications. © 2014 Elsevier B.V. All rights reserved.

  5. Cerebral Palsy Litigation

    PubMed Central

    Sartwelle, Thomas P.

    2015-01-01

    The cardinal driver of cerebral palsy litigation is electronic fetal monitoring, which has continued unabated for 40 years. Electronic fetal monitoring, however, is based on 19th-century childbirth myths, a virtually nonexistent scientific foundation, and has a false positive rate exceeding 99%. It has not affected the incidence of cerebral palsy. Electronic fetal monitoring has, however, increased the cesarian section rate, with the expected increase in mortality and morbidity risks to mothers and babies alike. This article explains why electronic fetal monitoring remains endorsed as efficacious in the worlds’ labor rooms and courtrooms despite being such a feeble medical modality. It also reviews the reasons professional organizations have failed to condemn the use of electronic fetal monitoring in courtrooms. The failures of tort reform, special cerebral palsy courts, and damage limits to stem the escalating litigation are discussed. Finally, the authors propose using a currently available evidence rule—the Daubert doctrine that excludes “junk science” from the courtroom—as the beginning of the end to cerebral palsy litigation and electronic fetal monitoring’s 40-year masquerade as science. PMID:25183322

  6. Cerebral Malaria.

    PubMed

    Marsden, P D; Bruce-Chwatt, L J

    1975-01-01

    Cerebral malaria is an acute diffuse encephalopathy associated only with Plasmodium falciparum. It is probably a consequence of the rapid proliferation of the parasites in the body of man in relation to red cell invasion, and results in stagnation of blood flow in cerebralcapillaries with thromobotic occlusion of large numbers of cerebral capillaries. The subsequent cerebral pathology is cerebral infarction with haemorrhage and cerebral oedema. The wide prevalence of P. falciparum in highly endemic areas results in daily challenges to patients from several infected mosquitoes. It is thus important to understand the characteristics of P. falciparum, since this is one of the most important protozoan parasites of man and severe infection from it constitutes one of the few real clinical emergencies in tropical medicine. One of the more important aspects of the practice of medicine in the tropics is to establish a good understanding of the pattern of medical practice in that area. This applies to malaria as well as to other diseases. The neophyte might be somewhat surprised to learn, for example that an experienced colleague who lives in a holoendemic malarious area such as West Africa, sees no cerebral malaria. But the explanation is simple when the doctor concerned has a practice which involves treating adults only. Cerebral malaria is rare in adults, because in highly endemic areas, by the age of 1 year most of the infants in a group under study have already experienced their first falciparum infection. By the time they reach adult life, they have a solid immunity against severe falciparum infections. In fact, "clinical malaria" could occur in such a group under only two circumstances: 1) in pregnancy, a patent infection with P. falciparum might develop, probably due to an IgG drain across the placenta to the foetus;2) in an individual who has constantly taken antimalarials and who may have an immunity at such a low level that when antimalarial therapy is interrupted

  7. A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells

    PubMed Central

    Pagenstecher, Axel; Stahl, Sonja; Sure, Ulrich; Felbor, Ute

    2009-01-01

    Cavernous vascular malformations occur with a frequency of 1:200 and can cause recurrent headaches, seizures and hemorrhagic stroke if located in the brain. Familial cerebral cavernous malformations (CCMs) have been associated with germline mutations in CCM1/KRIT1, CCM2 or CCM3/PDCD10. For each of the three CCM genes, we here show complete localized loss of either CCM1, CCM2 or CCM3 protein expression depending on the inherited mutation. Cavernous but not adjacent normal or reactive endothelial cells of known germline mutation carriers displayed immunohistochemical negativity only for the corresponding CCM protein but not for the two others. In addition to proving loss of function at the protein level, our data are the first to demonstrate endothelial cell mosaicism within cavernous tissues and provide clear pathogenetic evidence that the endothelial cell is the cell of disease origin. PMID:19088124

  8. A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells.

    PubMed

    Pagenstecher, Axel; Stahl, Sonja; Sure, Ulrich; Felbor, Ute

    2009-03-01

    Cavernous vascular malformations occur with a frequency of 1:200 and can cause recurrent headaches, seizures and hemorrhagic stroke if located in the brain. Familial cerebral cavernous malformations (CCMs) have been associated with germline mutations in CCM1/KRIT1, CCM2 or CCM3/PDCD10. For each of the three CCM genes, we here show complete localized loss of either CCM1, CCM2 or CCM3 protein expression depending on the inherited mutation. Cavernous but not adjacent normal or reactive endothelial cells of known germline mutation carriers displayed immunohistochemical negativity only for the corresponding CCM protein but not for the two others. In addition to proving loss of function at the protein level, our data are the first to demonstrate endothelial cell mosaicism within cavernous tissues and provide clear pathogenetic evidence that the endothelial cell is the cell of disease origin.

  9. Cerebral White Matter

    PubMed Central

    Schmahmann, Jeremy D.; Smith, Eric E.; Eichler, Florian S.; Filley, Christopher M.

    2013-01-01

    Lesions of the cerebral white matter (WM) result in focal neurobehavioral syndromes, neuropsychiatric phenomena, and dementia. The cerebral WM contains fiber pathways that convey axons linking cerebral cortical areas with each other and with subcortical structures, facilitating the distributed neural circuits that subserve sensorimotor function, intellect, and emotion. Recent neuroanatomical investigations reveal that these neural circuits are topographically linked by five groupings of fiber tracts emanating from every neocortical area: (1) cortico-cortical association fibers; (2) corticostriatal fibers; (3) commissural fibers; and cortico-subcortical pathways to (4) thalamus and (5) pontocerebellar system, brain stem, and/or spinal cord. Lesions of association fibers prevent communication between cortical areas engaged in different domains of behavior. Lesions of subcortical structures or projection/striatal fibers disrupt the contribution of subcortical nodes to behavior. Disconnection syndromes thus result from lesions of the cerebral cortex, subcortical structures, and WM tracts that link the nodes that make up the distributed circuits. The nature and the severity of the clinical manifestations of WM lesions are determined, in large part, by the location of the pathology: discrete neurological and neuropsychiatric symptoms result from focal WM lesions, whereas cognitive impairment across multiple domains—WM dementia—occurs in the setting of diffuse WM disease. We present a detailed review of the conditions affecting WM that produce these neurobehavioral syndromes, and consider the pathophysiology, clinical effects, and broad significance of the effects of aging and vascular compromise on cerebral WM, in an attempt to help further the understanding, diagnosis, and treatment of these disorders. PMID:18990132

  10. Coulometric and spectroscopic analysis of the purified cytochrome d complex of Escherichia coli: evidence for the identification of "cytochrome a1" as cytochrome b595.

    PubMed

    Lorence, R M; Koland, J G; Gennis, R B

    1986-05-06

    Coulometric and spectroscopic analyses were performed on the three cytochrome components (cytochrome d, cytochrome b558, and the cytochrome previously described as cytochrome a1) of the purified cytochrome d complex, a terminal oxidase of the Escherichia coli aerobic respiratory chain. On the basis of heme extraction, spectroscopic, and coulometric data, the "cytochrome a1" component was identified as a b-type cytochrome: cytochrome b595. The pyridine hemochromogen technique revealed the presence of two molecules of protoheme IX per cytochrome d complex. This quantity of protoheme IX fully accounted for the sum of the cytochrome b558 and cytochrome b595 components as determined coulometrically. The renaming of cytochrome a1 as cytochrome b595 was further indicated by the lack of any heme a in the complex and by its resolved reduced-minus-oxidized spectrum. The latter was found to be similar to that of cytochrome c peroxidase, which contains protoheme IX. Coulometric titrations and carbon monoxide binding titrations revealed that there are two molecules of cytochrome d per complex. A convenient measurement of the amount of cytochrome b558 was found to be the beta-band at 531 nm since cytochrome b558 was observed to be the only component of the cytochrome d complex with a peak at this wavelength. By use of this method and the extinction coefficient for the purified cytochrome b558, it was estimated that there is one molecule of cytochrome b595 and one of cytochrome b558 per cytochrome complex.

  11. Cerebral vascular findings in PAPA syndrome: cerebral arterial vasculopathy or vasculitis and a posterior cerebral artery dissecting aneurysm.

    PubMed

    Khatibi, Kasra; Heit, Jeremy J; Telischak, Nicholas A; Elbers, Jorina M; Do, Huy M

    2015-06-24

    A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.

  12. Cerebral vascular findings in PAPA syndrome: cerebral arterial vasculopathy or vasculitis and a posterior cerebral artery dissecting aneurysm.

    PubMed

    Khatibi, Kasra; Heit, Jeremy J; Telischak, Nicholas A; Elbers, Jorina M; Do, Huy M

    2016-08-01

    A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.

  13. Mitochondrial cytochrome c biogenesis: no longer an enigma.

    PubMed

    Babbitt, Shalon E; Sutherland, Molly C; San Francisco, Brian; Mendez, Deanna L; Kranz, Robert G

    2015-08-01

    Cytochromes c (cyt c) and c1 are heme proteins that are essential for aerobic respiration. Release of cyt c from mitochondria is an important signal in apoptosis initiation. Biogenesis of c-type cytochromes involves covalent attachment of heme to two cysteines (at a conserved CXXCH sequence) in the apocytochrome. Heme attachment is catalyzed in most mitochondria by holocytochrome c synthase (HCCS), which is also necessary for the import of apocytochrome c (apocyt c). Thus, HCCS affects cellular levels of cyt c, impacting mitochondrial physiology and cell death. Here, we review the mechanisms of HCCS function and the roles of heme and residues in the CXXCH motif. Additionally, we consider concepts emerging within the two prokaryotic cytochrome c biogenesis pathways.

  14. Isolation of Rhizobium phaseoli Tn5-induced mutants with altered expression of cytochrome terminal oxidases o and aa3.

    PubMed Central

    Soberón, M; Membrillo-Hernández, J; Aguilar, G R; Sánchez, F

    1990-01-01

    Two Rhizobium phaseoli mutants affected in cytochrome expression were obtained by Tn5-mob mutagenesis of the wild-type strain (CE3). Mutant strain CFN031 expressed sevenfold less cytochrome o in culture, expressed cytochrome aa3 under microaerophilic culture conditions, in contrast to strain CE3, and was affected in its vegetative growth properties and proliferation inside plant host cells. Mutant CFN037 expressed cytochrome aa3 under microaerophilic culture conditions, while bacteroid development and nitrogen fixation occurred earlier than in strain CE3. Images FIG. 2 PMID:2155209

  15. The Cytochrome P450 Homepage

    PubMed Central

    2009-01-01

    The Cytochrome P450 Homepage is a universal resource for nomenclature and sequence information on cytochrome P450 (CYP) genes. The site has been in continuous operation since February 1995. Currently, naming information for 11,512 CYPs are available on the web pages. The P450 sequences are manually curated by David Nelson, and the nomenclature system conforms to an evolutionary scheme such that members of CYP families and subfamilies share common ancestors. The organisation and content of the Homepage are described. PMID:19951895

  16. Evolution of the couple cytochrome c and cytochrome c oxidase in Primates

    PubMed Central

    Pierron, Denis; Wildman, Derek E.; Hüttemann, Maik; Letellier, Thierry; Grossman, Lawrence I.

    2013-01-01

    Mitochondrial energy metabolism has been affected by a broad set of ancient and recent evolutionary events. The oldest example is the endosymbiosis theory that led to mitochondria and a recently proposed example is adaptation to cold climate by anatomically modern human lineages. Mitochondrial energy metabolism has also been associated with an important area in anthropology and evolutionary biology, brain enlargement in human evolution. Indeed, several studies have pointed to the need for a major metabolic rearrangement to supply a sufficient amount of energy for brain development in primates. The gene encoding for the coupled cytochrome c (cyt c) / cytochrome c oxidase (COX, complex IV, EC 1.9.3.1) seems to have an exceptional pattern of evolution in the anthropoid lineage. It has been proposed that this evolution was linked to the rearrangement of energy metabolism needed for brain enlargement. This hypothesis is reinforced by the fact that the COX enzyme was proposed to have a large role in control of the respiratory chain and thereby global energy production. After summarizing major events that occurred during the evolution of COX and cytochrome c on the primate lineage, we review the different evolutionary forces that could have influenced primate COX evolution and discuss the probable causes and consequence of this evolution. Finally, we discuss and review the co-occurring primate phenotypic evolution. PMID:22729859

  17. Acute cerebral vascular accident associated with hyperperfusion.

    PubMed

    Soin, J S; Burdine, J A

    1976-01-01

    Cerebral radionuclide angiography can demonstrate decreased or normal radioactivity in the affected region during the arterial phase in patients who have sustained a cerebral vascular accident and thus enhances the diagnostic specificity of the static brain image. In an occasional patient, however, a seemingly paradoxical pattern of regional hyperperfusion with a return to normal or subnormal perfusion following the acute phase has been observed. This phenomenon, called "luxury perfusion," has been defined using intra-arterial 133Xe for semiquantitative cerebral blood flow measurements and should be kept in mind as a potentially misleading cerebral imaging pattern.

  18. Hepatic and intestinal cytochrome P-450, glutathione-S-transferase and UDP-glucuronosyl transferase are affected by six types of dietary fiber in rats inoculated with human whole fecal flora.

    PubMed

    Roland, N; Nugon-Baudon, L; Flinois, J P; Beaune, P

    1994-09-01

    The effects of six different sources of dietary fiber (inulin, wheat brain, carrot, cocoa, pea and oat fiber) on hepatic and intestinal cytochrome P-450 (EC 1.14.14.1), glutathione-S-transferase (GSH-T, EC 2.5.1.18) and UDP-glucuronosyl transferase (UDPG-T, EC 2.4.1.17) were studied using germ-free F344 rats subsequently inoculated with a human whole fecal flora. In the liver, the total concentration of P-450 was significantly lower in the wheat bran-fed group than in the carrot-fed group. The 2E1 form of P-450, involved in nitrosamine metabolism, was enhanced in the carrot-fed group compared with those fed most other types of fiber. Compared with the pea-fed group, rats fed cocoa had a lower constitutive 2C11 form and a higher 1A2 form. A very high concentration of small intestinal 1A1 form--involved in "toxication" reactions--was observed in rats fed cocoa. The specific activity of hepatic GSH-T was significantly higher in rats fed inulin than in all other groups, except the carrot-fed group. In the colon, GSH-T specific activity was twice as high in the oat-fed group as in the wheat bran-fed counterpart. Small intestinal GSH-T activity and hepatic and intestinal UDPG-T activities were unaffected by diet. Results are discussed in relation to potential health benefits.

  19. Primary structure determination of two cytochromes c2: close similarity to functionally unrelated mitochondrial cytochrome C.

    PubMed Central

    Ambler, R P; Meyer, T E; Kamen, M D

    1976-01-01

    The amino-acid sequences of the cytochromes c2 from the photosynthetic non-sulfur purple bacteria Rhodomicrobium vannielii and Rhodopseudomonas viridis have been determined. Only a single residue deletion (at position 11 in horse cytochrome c) is necessary to align the sequences with those of mitochondrial cytochromes c. The overall sequence similarity between these cytochromes c2 and mitochondrial cytochromes c is closer than that between mitochondrial cytochromes c and the other cytochromes c2 of known sequence, and in the latter multiple insertions and deletions must be postulated before a match can be obtained. Nevertheless, these two cytochromes c2 show no better reactivity with the mitochondrial cytochrome c oxidase than do the less well-matched cytochromes c2. The bearing of these findings on possible evolutionary relationship between mitochondria and prokaryotes is discussed. PMID:174109

  20. Sequence of b cytochromes relative to ubiquinone in the electron transport chain of Escherichia coli.

    PubMed Central

    Downie, J A; Cox, G B

    1978-01-01

    A ubiquinone-deficient mutant, carrying mutations in two genes affecting ubiquinone biosynthesis, has been used, in comparison with a normal strain, to determine the sequence of some of the components of the electron transport chain of Escherichia coli. The amounts of cytochromes reduced during aerobic steady-state conditions were estimated by comparing low-temperature difference spectra of normal or ubiquinone-deficient membranes with either D-lactate or reduced nicotinamide adenine dinucleotide as substrate. From the amounts of cytochromes reduced it was concluded that ubiquinone functions at two sites, one site being between the dehydrogenases and cytochromes and the second site being after cytochromes b562 and b556 but before cytochromes b558, d, and o. The scheme proposed is discussed in relation to the Mitchell protonmotive ubiquinone cycle. PMID:203570

  1. Brain-Derived Neurotrophic Factor Val66Met Polymorphism Affects the Relationship Between an Anxiety-Related Personality Trait and Resting Regional Cerebral Blood Flow.

    PubMed

    Wei, Shau-Ming; Eisenberg, Daniel P; Nabel, Katherine G; Kohn, Philip D; Kippenhan, J Shane; Dickinson, Dwight; Kolachana, Bhaskar; Berman, Karen F

    2017-03-01

    Brain-derived neurotrophic factor (BDNF) is an important modulator of constitutive stress responses mediated by limbic frontotemporal circuits, and its gene contains a functional polymorphism (Val66Met) that may influence trait stress sensitivity. Reports of an association of this polymorphism with anxiety-related personality traits have been controversial and without clear neurophysiological support. We, therefore, determined the relationship between resting regional cerebral blood flow (rCBF) and a well-validated measure of anxiety-related personality, the TPQ Harm Avoidance (HA) scale, as a function of BDNF Val66Met genotype. Sixty-four healthy participants of European ancestry underwent resting H215O positron emission tomography scans. For each genotype group separately, we first determined the relationship between participants' HA scores and their resting rCBF values in each voxel across the entire brain, and then directly compared these HA-rCBF relationships between Val66Met genotype groups. HA-rCBF relationships differed between Val homozygotes and Met carriers in several regions relevant to stress regulation: subgenual cingulate, orbital frontal cortex, and the hippocampal/parahippocampal region. In each of these areas, the relationship was positive in Val homozygotes and negative in Met carriers. These data demonstrate a coupling between trait anxiety and basal resting blood flow in frontolimbic neurocircuitry that may be determined in part by genetically mediated BDNF signaling. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. Cytochrome aa3 in Haloferax volcanii

    PubMed Central

    Tanaka, Mikiei; Ogawa, Naohide; Ihara, Kunio; Sugiyama, Yasuo; Mukohata, Yasuo

    2002-01-01

    A cytochrome in an extremely halophilic archaeon, Haloferax volcanii, was purified to homogeneity. This protein displayed a redox difference spectrum that is characteristic of a-type cytochromes and a CN− complex spectrum that indicates the presence of heme a and heme a3. This cytochrome aa3 consisted of 44- and 35-kDa subunits. The amino acid sequence of the 44-kDa subunit was similar to that of the heme-copper oxidase subunit I, and critical amino acid residues for metal binding, such as histidines, were highly conserved. The reduced cytochrome c partially purified from the bacterial membrane fraction was oxidized by the cytochrome aa3, providing physiological evidence for electron transfer from cytochrome c to cytochrome aa3 in archaea. PMID:11790755

  3. Cerebral Disorders of Calves.

    PubMed

    Dore, Vincent; Smith, Geof

    2017-03-01

    Neurologic diseases of the cerebrum are relatively common in cattle. In calves, the primary cerebral disorders are polioencephalomalacia, meningitis, and sodium toxicity. Because diagnostic testing is not always readily available, the practitioner must often decide on a course of treatment based on knowledge of the likely disease, as well as his or her own clinical experience. This is particularly true with neurologic diseases in which the prognosis is often poor and euthanasia may be the most humane outcome. This article reviews the most common diseases affecting the cerebrum of calves with a focus on pathophysiology, diagnosis, and treatment.

  4. Cytochromes P450 in Nanodiscs

    PubMed Central

    Denisov, Ilia G.; Sligar, Stephen G.

    2010-01-01

    Nanodiscs have proven to be a versatile tool for the study all types of membrane proteins, including receptors, transporters, enzymes and viral antigens. The self-assembled Nanodisc system provides a robust and common means for rendering these targets soluble in aqueous media while providing a native like bilayer environment that maintains functional activity. This system has thus provided a means for studying the extensive collection of membrane bound cytochromes P450 with the same biochemical and biophysical tools that have been previously limited to use with the soluble P450s. These include a plethora of spectroscopic, kinetic and surface based methods. Significant improvements in homogeneity and stability of these preparations open new possibilities for detailed analysis of equilibrium and steady-state kinetic characteristics of catalytic mechanisms of human cytochromes P450 involved in xenobiotic metabolism and in steroid biosynthesis. The experimental methods developed for physico-chemical and functional studies of membrane cytochromes P450 incorporated in Nanodiscs allow for more detailed understanding of the scientific questions along the lines pioneered by Professor Klaus Ruckpaul and his array of colleagues and collaborators. PMID:20685623

  5. Genes involved in the formation and assembly of rhizobial cytochromes and their role in symbiotic nitrogen fixation.

    PubMed

    Delgado, M J; Bedmar, E J; Downie, J A

    1998-01-01

    Rhizobia fix nitrogen in a symbiotic association with leguminous plants and this occurs in nodules. A low-oxygen environment is needed for nitrogen fixation, which paradoxically has a requirement for rapid respiration to produce ATP. These conflicting demands are met by control of oxygen flux and production of leghaemoglobin (an oxygen carrier) by the plant, coupled with the expression of a high-affinity oxidase by the nodule bacteria (bacteroids). Many of the bacterial genes encoding cytochrome synthesis and assembly have been identified in a variety of rhizobial strains. Nitrogen-fixing bacteroids use a cytochrome cbb3-type oxidase encoded by the fixNOQP operon; electron transfer to this high-affinity oxidase is via the cytochrome bc1 complex. During free-living growth, electron transport from the cytochrome bc1 complex to cytochrome aa3 occurs via a transmembrane cytochrome c (CycM). In some rhizobia (such as Bradyrhizobium japonicum) there is a second cytochrome oxidase that also requires electron transport via the cytochrome bc1 complex. In parallel with these cytochrome c oxidases there are quinol oxidases that are expressed during free-living growth. A cytochrome bb3 quinol oxidase is thought to be present in B. japonicum; in Rhizobium leguminosarum, Rhizobium etli and Azorhizobium caulinodans cytochrome d-type oxidases have been identified. Spectroscopic data suggest the presence of a cytochrome o-type oxidase in several rhizobia, although the absence of haem O in B. japonicum may indicate that the absorption attributed to cytochrome o could be due to a high-spin cytochrome b in a cytochrome bb3-type oxidase. In some rhizobia, mutation of genes involved in cytochrome c assembly does not strongly affect growth, presumably because the bacteria utilize the cytochrome c-independent quinol oxidases. In this review, we outline the work on various rhizobial mutants affected in different components of the electron transport pathways, and the effects of these

  6. Encephaloduroarteriosynangiosis for cerebral proliferative angiopathy with cerebral ischemia.

    PubMed

    Kono, Kenichi; Terada, Tomoaki

    2014-12-01

    Cerebral proliferative angiopathy (CPA) is a rare clinical entity. This disorder is characterized by diffuse vascular abnormalities with intermingled normal brain parenchyma, and is differentiated from classic arteriovenous malformations. The management of CPA in patients presenting with nonhemorrhagic neurological deficits due to cerebral ischemia is challenging and controversial. The authors report a case of adult CPA with cerebral ischemia in which neurological deficits were improved after encephaloduroarteriosynangiosis (EDAS). A 28-year-old man presented with epilepsy. Magnetic resonance imaging and angiography showed a diffuse vascular network (CPA) in the right hemisphere. Antiepileptic medications were administered. Four years after the initial onset of epilepsy, the patient's left-hand grip strength gradually decreased over the course of 1 year. The MRI studies showed no infarcts, but technetium-99m-labeled ethyl cysteinate dimer ((99m)Tc-ECD) SPECT studies obtained with acetazolamide challenge demonstrated hypoperfusion and severely impaired cerebrovascular reactivity over the affected hemisphere. This suggested that the patient's neurological deficits were associated with cerebral ischemia. The authors performed EDAS for cerebral ischemia, and the patient's hand grip strength gradually improved after the operation. Follow-up angiography studies obtained 7 months after the operation showed profound neovascularization through the superficial temporal artery and the middle meningeal artery. A SPECT study showed slight improvement of hypoperfusion at the focal region around the right motor area, indicating clinical improvement from the operation. The authors conclude that EDAS may be a treatment option for CPA-related hypoperfusion.

  7. Cerebral Tissue Oxygenation during Immediate Neonatal Transition and Resuscitation

    PubMed Central

    Pichler, Gerhard; Schmölzer, Georg M.; Urlesberger, Berndt

    2017-01-01

    This article provides a review of cerebral tissue oxygenation during immediate transition after birth in human neonates. Recommended routine monitoring, especially if resuscitation is needed, during this period includes arterial oxygen saturation and heart rate measured by pulse oximetry and electrocardiogram. However, there is increasing interest to monitor in addition with near-infrared spectroscopy (NIRS) the oxygenation of the brain. There is a different pattern of increase between cerebral tissue oxygenation and arterial oxygen saturation during the immediate transition, with cerebral tissue oxygenation reaching a plateau faster than arterial oxygen saturation. Differences can be explained, since cerebral tissue oxygenation is not only affected by arterial oxygen saturation but also by cerebral blood flow, hemoglobin content, and cerebral oxygen consumption. Normal values have already been established for different devices, gestational ages, and modes of delivery in neonates without any medical support. Cerebral hypoxia during immediate transition might cause brain damage. In preterm neonates with cerebral hemorrhage evolving in the first week after birth, the cerebral tissue oxygenation is already lower in the first minutes after birth compared to preterm neonates without cerebral hemorrhage. Using cerebral NIRS in combination with intervention guidelines has been shown to reduce the burden of cerebral hypoxia in preterm neonates. Cerebral tissue oxygenation during immediate transition seems to have an impact on outcome, whereby NIRS monitoring is feasible and has the advantage of continuous, non-invasive recording. The impact of NIRS monitoring and interventions on short- and long-term outcomes still need to be evaluated. PMID:28280719

  8. Cerebral Tissue Oxygenation during Immediate Neonatal Transition and Resuscitation.

    PubMed

    Pichler, Gerhard; Schmölzer, Georg M; Urlesberger, Berndt

    2017-01-01

    This article provides a review of cerebral tissue oxygenation during immediate transition after birth in human neonates. Recommended routine monitoring, especially if resuscitation is needed, during this period includes arterial oxygen saturation and heart rate measured by pulse oximetry and electrocardiogram. However, there is increasing interest to monitor in addition with near-infrared spectroscopy (NIRS) the oxygenation of the brain. There is a different pattern of increase between cerebral tissue oxygenation and arterial oxygen saturation during the immediate transition, with cerebral tissue oxygenation reaching a plateau faster than arterial oxygen saturation. Differences can be explained, since cerebral tissue oxygenation is not only affected by arterial oxygen saturation but also by cerebral blood flow, hemoglobin content, and cerebral oxygen consumption. Normal values have already been established for different devices, gestational ages, and modes of delivery in neonates without any medical support. Cerebral hypoxia during immediate transition might cause brain damage. In preterm neonates with cerebral hemorrhage evolving in the first week after birth, the cerebral tissue oxygenation is already lower in the first minutes after birth compared to preterm neonates without cerebral hemorrhage. Using cerebral NIRS in combination with intervention guidelines has been shown to reduce the burden of cerebral hypoxia in preterm neonates. Cerebral tissue oxygenation during immediate transition seems to have an impact on outcome, whereby NIRS monitoring is feasible and has the advantage of continuous, non-invasive recording. The impact of NIRS monitoring and interventions on short- and long-term outcomes still need to be evaluated.

  9. [Cerebral palsy].

    PubMed

    Malagón Valdez, Jorge

    2007-01-01

    The term cerebral palsy (CP), is used for a great number of clinical neurological syndromes. The syndromes are characterized by having a common cause, motor defects. It is important, because they can cause a brain damage by presenting motor defects and some associated deficiencies, such as mental deficiency, epilepsy, language and visual defects and pseudobulbar paralysis, with the non-evolving fact. Some authors prefer using terms such as "non-evolving encephalopathies". In the treatment the utility of prevention programs of early stimulation and special rehabilitation methods, and treatment of associated deficiencies such as epilepsy, mental deficiency, language, audition and visual problems, and the attention deficit improve the prognosis in an important way. The prognosis depends on the severity of the disease and the associated manifestations.

  10. Cytochrome allelic variants and clopidogrel metabolism in cardiovascular diseases therapy.

    PubMed

    Jarrar, Mohammed; Behl, Shalini; Manyam, Ganiraju; Ganah, Hany; Nazir, Mohammed; Nasab, Reem; Moustafa, Khaled

    2016-06-01

    Clopidogrel and aspirin are among the most prescribed dual antiplatelet therapies to treat the acute coronary syndrome and heart attacks. However, their potential clinical impacts are a subject of intense debates. The therapeutic efficiency of clopidogrel is controlled by the actions of hepatic cytochrome P450 (CYPs) enzymes and impacted by individual genetic variations. Inter-individual polymorphisms in CYPs enzymes affect the metabolism of clopidogrel into its active metabolites and, therefore, modify its turnover and clinical outcome. So far, clinical trials fail to confirm higher or lower adverse cardiovascular effects in patients treated with combinations of clopidogrel and proton pump inhibitors, compared with clopidogrel alone. Such inconclusive findings may be due to genetic variations in the cytochromes CYP2C19 and CYP3A4/5. To investigate potential interactions/effects of these cytochromes and their allele variants on the treatment of acute coronary syndrome with clopidogrel alone or in combination with proton pump inhibitors, we analyze recent literature and discuss the potential impact of the cytochrome allelic variants on cardiovascular events and stent thrombosis treated with clopidogrel. The diversity of CYP2C19 polymorphisms and prevalence span within various ethnic groups, subpopulations and demographic areas are also debated.

  11. A novel mutation in the mitochondrial DNA cytochrome b gene (MTCYB) in a patient with Prader Willi syndrome.

    PubMed

    Yiş, Uluç; Ezgü, Fatih Süheyl; Karakaya, Pakize; Polat, İpek; Arslan, Nur; Çankaya, Tufan; Bozkaya, Özlem Giray; Kurul, Semra Hız

    2015-03-01

    In recent years, it has been suggested that defects in energy metabolism may accompany Prader Willi syndrome. Mutations in the mitochondrial cytochrome b gene have been commonly associated isolated mitochondrial myopathy and exercise intolerance, rarely with multisystem disorders. The authors describe a novel mutation (mt. 15209T>C) in mitochondrial cytochrome b gene in a 2-year-old girl with Prader-Willi syndrome with a clinical history of lactic acidosis attacks, renal sodium loss, hepatopathy, progressive cerebral atrophy, and sudden death. The authors suggest that atypical clinical findings in patients with Prader-Willi syndrome should direct the physician to search for a mitochondrial disease.

  12. Effects of membrane mimetics on cytochrome P450-cytochrome b5 interactions characterized by NMR spectroscopy.

    PubMed

    Zhang, Meng; Huang, Rui; Im, Sang-Choul; Waskell, Lucy; Ramamoorthy, Ayyalusamy

    2015-05-15

    Mammalian cytochrome P450 (P450) is a membrane-bound monooxygenase whose catalytic activities require two electrons to be sequentially delivered from its redox partners: cytochrome b5 (cytb5) and cytochrome P450 reductase, both of which are membrane proteins. Although P450 functional activities are known to be affected by lipids, experimental evidence to reveal the effect of membrane on P450-cytb5 interactions is still lacking. Here, we present evidence for the influence of phospholipid bilayers on complex formation between rabbit P450 2B4 (CYP2B4) and rabbit cytb5 at the atomic level, utilizing NMR techniques. General line broadening and modest chemical shift perturbations of cytb5 resonances characterize CYP2B4-cytb5 interactions on the intermediate time scale. More significant intensity attenuation and a more specific protein-protein binding interface are observed in bicelles as compared with lipid-free solution, highlighting the importance of the lipid bilayer in stabilizing stronger and more specific interactions between CYP2B4 and cytb5, which may lead to a more efficient electron transfer. Similar results observed for the interactions between CYP2B4 lacking the transmembrane domain (tr-CYP2B4) and cytb5 imply interactions between tr-CYP2B4 and the membrane surface, which might assist in CYP2B4-cytb5 complex formation by orienting tr-CYP2B4 for efficient contact with cytb5. Furthermore, the observation of weak and nonspecific interactions between CYP2B4 and cytb5 in micelles suggests that lipid bilayer structures and low curvature membrane surface are preferable for CYP2B4-cytb5 complex formation. Results presented in this study provide structural insights into the mechanism behind the important role that the lipid bilayer plays in the interactions between P450s and their redox partners. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Cytochrome Electron Transfer and Biomolecular Electronics.

    DTIC Science & Technology

    1988-06-22

    polarograms of cytochrome c3 "a) DvM: Desulfovibrio vulgaris Miyazaki F (solid line,rmeasured; dots, si ulated) .. b) DvH: Desulfovibrio vulgaris ...Miyazaki); 2. D. vulgaris (H ldenborough); 3. D. sulfurlcans (Norway) and % 4. D. gigas. The macroscopic redox potentials for each of the hemes in the...Structure of Cytochrome C 3 Four cytochromes C have been selected for study: 1. D. vulgaris (Miyazaki) DvM) ; 2. D. vulgaris (Hildenborough) (DvH); 3. D

  14. Direct inhibitions of the activities of steroidogenic cytochrome P-450 mono-oxygenase systems by anticonvulsants.

    PubMed

    Ohnishi, T; Ichikawa, Y

    1997-01-01

    The effects of anticonvulsants on the activities of cytochromes P-450(17alpha,lyase) (CYP17), P-450arom (CYP19), P-450C21 (CYP21), P-450SCC (CYP11A1), and P-450(11beta) (CYP11B1) mono-oxygenase systems were studied using rat testicular microsomes, human placental microsomes, bovine adrenocortical microsomes, bovine adrenocortical mitochondria and purified cytochrome P-450(11beta). Phenytoin, clonazepam and carbamazepine inhibited the steroidogenesis catalysed by these cytochrome P-450 mono-oxygenase systems and the Ki values for each anticonvulsant were determined. Neither hydantoin nor sodium valproate inhibited the activities of steroidogenic cytochromes P-450. When the activities of cytochromes P-450arom and P-450C21 were measured in the presence of anticonvulsants, the Ki values (0.15 mM) for phenytoin were close to the plasma concentration of phenytoin under therapeutic conditions. Phenytoin, clonazepam and carbamazepine directly inhibited the monooxygenase activities of cytochromes P-450, because they did not affect the activities of NADPH-cytochrome P-450 reductase, NADPH-adrenoferredoxin reductase and adrenoferredoxin.

  15. DAC is involved in the accumulation of the cytochrome b6/f complex in Arabidopsis.

    PubMed

    Xiao, Jianwei; Li, Jing; Ouyang, Min; Yun, Tao; He, Baoye; Ji, Daili; Ma, Jinfang; Chi, Wei; Lu, Congming; Zhang, Lixin

    2012-12-01

    The biogenesis and assembly of photosynthetic multisubunit protein complexes is assisted by a series of nucleus-encoded auxiliary protein factors. In this study, we characterize the dac mutant of Arabidopsis (Arabidopsis thaliana), which shows a severe defect in the accumulation of the cytochrome b(6)/f complex, and provide evidence suggesting that the efficiency of cytochrome b(6)/f complex assembly is affected in the mutant. DAC is a thylakoid membrane protein with two predicted transmembrane domains that is conserved from cyanobacteria to vascular plants. Yeast (Saccharomyces cerevisiae) two-hybrid and coimmunoprecipitation analyses revealed a specific interaction between DAC and PetD, a subunit of the cytochrome b(6)/f complex. However, DAC was found not to be an intrinsic component of the cytochrome b(6)/f complex. In vivo chloroplast protein labeling experiments showed that the labeling rates of the PetD and cytochrome f proteins were greatly reduced, whereas that of the cytochrome b(6) protein remained normal in the dac mutant. DAC appears to be a novel factor involved in the assembly/stabilization of the cytochrome b(6)/f complex, possibly through interaction with the PetD protein.

  16. Canine cytochrome P-450 pharmacogenetics.

    PubMed

    Court, Michael H

    2013-09-01

    The cytochrome P-450 (CYP) drug metabolizing enzymes are essential for the efficient elimination of many clinically used drugs. These enzymes typically display high interindividual variability in expression and function resulting from enzyme induction, inhibition, and genetic polymorphism thereby predisposing patients to adverse drug reactions or therapeutic failure. There are also substantial species differences in CYP substrate specificity and expression that complicate direct extrapolation of information from humans to veterinary species. This article reviews the available published data regarding the presence and impact of genetic polymorphisms on CYP-dependent drug metabolism in dogs in the context of known human-dog CYP differences. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Cytochrome P450-activated prodrugs

    PubMed Central

    Ortiz de Montellano, Paul R

    2013-01-01

    A prodrug is a compound that has negligible, or lower, activity against a specified pharmacological target than one of its major metabolites. Prodrugs can be used to improve drug delivery or pharmacokinetics, to decrease toxicity, or to target the drug to specific cells or tissues. Ester and phosphate hydrolysis are widely used in prodrug design because of their simplicity, but such approaches are relatively ineffective for targeting drugs to specific sites. The activation of prodrugs by the cytochrome P450 system provides a highly versatile approach to prodrug design that is particularly adaptable for targeting drug activation to the liver, to tumors or to hypoxic tissues. PMID:23360144

  18. Cytochrome c Adducts with PCB Quinoid Metabolites

    PubMed Central

    Li, Miao; Teesch, Lynn M.; Murry, Daryl J.; Pope, R. Marshal; Li, Yalan; Robertson, Larry W.; Ludewig, Gabriele

    2015-01-01

    PCBs are a group of 209 individual congeners widely used as industrial chemicals. PCBs are found as by-products in dye and paint manufacture and are legacy, ubiquitous and persistent as human and environmental contaminants. PCBs with fewer chlorine atoms may be metabolized to hydroxy- and dihydroxy- metabolites and further oxidized to quinoid metabolites both in vitro and in vivo. Specifically, quinoid metabolites may form adducts on nucleophilic sites within cells. We hypothesized that the PCB-quinones covalently bind to cytochrome c and thereby cause defects in the function of cytochrome c. In this study synthetic PCB quinones (2-(4’-chlorophenyl)-1,4-benzoquinone, 2-(3’, 5’-dichlorophenyl)-1,4-benzoquinone, 2-(3’,4’, 5’-trichlorophenyl)-1,4-benzoquinone, and 2-(4’-chlorophenyl)-3,6-dichloro-1,4-benzoquinone) were incubated with cytochrome c, and adducts were detected by LC-MS and MALDI TOF. SDS PAGE gel electrophoresis was employed to separate the adducted proteins, while trypsin digestion and LC-MS/MS were applied to identify the amino acid binding sites on cytochrome c. Conformation change of cytochrome c after binding with PCB3-para-quinone was investigated by SYBYL-X simulation and cytochrome c function was examined. We found that more than one molecule of PCB-quinone may bind to one molecule of cytochrome c. Lysine and glutamic acid were identified as the predominant binding sites. Software simulation showed conformation changes of adducted cytochrome c. Additionally, cross-linking of cytochrome c was observed on the SDS PAGE gel. Cytochrome c was found to be in the reduced form after incubation with PCB quinones. These data provide evidence that the covalent binding of PCB quinone metabolites to cytochrome c may be included among the toxic effects of PCBs. PMID:26062463

  19. Pathogenic mutations associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy differently affect Jagged1 binding and Notch3 activity via the RBP/JK signaling Pathway.

    PubMed

    Joutel, Anne; Monet, Marie; Domenga, Valérie; Riant, Florence; Tournier-Lasserve, Elisabeth

    2004-02-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited vascular dementia characterized by the degeneration of smooth-muscle cells in small cerebral arteries. CADASIL is caused by mutations in NOTCH3, one of the four mammalian homologs to the Drosophila melanogaster NOTCH gene. Disease-associated mutations are distributed throughout the 34 epidermal growth factor-like repeats (EGFRs) that compose the extracellular domain of the Notch3 receptor and result in a loss or a gain of a cysteine residue in one of these EGFRs. In human adults, Notch3 expression is highly restricted to vascular smooth-muscle cells. In patients with CADASIL, there is an abnormal accumulation of Notch3 in the vessel. Molecular pathways linking NOTCH3 mutations to degeneration of vascular smooth-muscle cells are as yet poorly understood. In this study, we investigated the effect of CADASIL mutations on Notch3 activity. We studied five naturally occurring mutations: R90C and C212S, located in the previously identified mutational hotspot EGFR2-5; C428S, shown in this study to be located in the ligand-binding domain EGFR10-11; and C542Y and R1006C, located in EGFR13 and EGFR26, respectively. All five mutant proteins were correctly processed. The C428S and C542Y mutant receptors exhibited a significant reduction in Jagged1-induced transcriptional activity of a RBP/JK responsive luciferase reporter, relative to wild-type Notch3. Impaired signaling activity of these two mutants arose through different mechanisms; the C428S mutant lost its Jagged1-binding ability, whereas C542Y retained it but exhibited an impaired presentation to the cell surface. In contrast, the R90C, C212S, and R1006C mutants retained the ability to bind Jagged1 and were associated with apparently normal levels of signaling activity. We conclude that mutations in Notch3 differently affect Jagged1 binding and Notch3 signaling via the RBP/JK pathway.

  20. The electron transfer complexes of cytochrome c peroxidase from Paracoccus denitrificans.

    PubMed

    Pettigrew, Graham W; Goodhew, Celia F; Cooper, Alan; Nutley, Margaret; Jumel, Kornelia; Harding, Stephen E

    2003-02-25

    We have used microcalorimetry and analytical ultracentrifugation to test the model proposed in Pettigrew et al. [(1999) J. Biol. Chem. 274, 11383-11389] for the binding of small cytochromes to the cytochrome c peroxidase of Paracoccus denitrificans. Both methods reveal complexity in behavior due to the presence of a monomer/dimer equilibrium in the peroxidase. In the presence of either Ca(2+), or higher ionic strength, this equilibrium is shifted to the dimer. Experiments to study complex formation with redox partners were performed in the presence of Ca(2+) in order to simplify the equilibria that had to be considered. The results of isothermal titration calorimetry reveal that the enzyme can bind two molecules of horse cytochrome c with K(d) values of 0.8 microM and 2.5 microM (at 25 degrees C, pH 6.0, I = 0.026) but only one molecule of Paracoccus cytochrome c-550 with a K(d) of 2.8 microM, molar binding ratios confirmed by ultracentrifugation. For both horse cytochrome c and Paracoccus cytochrome c-550, the binding is endothermic and driven by a large entropy change, a pattern consistent with the expulsion of water molecules from the interface. For horse cytochrome c, the binding is weakened 3-fold at I = 0.046 M due to a smaller entropy change, and this is associated with an increase in enzyme turnover. In contrast, neither the binding of cytochrome c-550 nor its oxidation rate is affected by raising the ionic strength in this range. We propose that, at low ionic strength, horse cytochrome c is trapped in a nonproductive orientation on a broad capture surface of the peroxidase.

  1. Dependence on NIRS source-detector spacing of cytochrome c oxidase response to hypoxia and hypercapnia in the adult brain.

    PubMed

    Kolyva, Christina; Ghosh, Arnab; Tachtsidis, Ilias; Highton, David; Smith, Martin; Elwell, Clare E

    2013-01-01

    Transcranial near-infrared spectroscopy (NIRS) provides an assessment of cerebral oxygen metabolism by monitoring concentration changes in oxidised cytochrome c oxidase Δ[oxCCO]. We investigated the response of Δ[oxCCO] to global changes in cerebral oxygen delivery at different source-detector separations in 16 healthy adults. Hypoxaemia was induced by delivery of a hypoxic inspired gas mix and hypercapnia by addition of 6 % CO2 to the inspired gases. A hybrid optical spectrometer was used to measure frontal cortex light absorption and scattering at discrete wavelengths and broadband light attenuation at 20, 25, 30 and 35 mm. Without optical scattering changes, a decrease in cerebral oxygen delivery, resulting from the reduction in arterial oxygen saturation during hypoxia, led to a decrease in Δ[oxCCO]. In contrast, Δ[oxCCO] increased when cerebral oxygen delivery increased due to increased cerebral blood flow during hypercapnia. In both cases the magnitude of the Δ[oxCCO] response increased from the detectors proximal (measuring superficial tissue layers) to the detectors distal (measuring deep tissue layers) to the broadband light source. We conclude that the Δ[oxCCO] response to hypoxia and hypercapnia appears to be dependent on penetration depth, possibly reflecting differences between the intra- and extracerebral tissue concentration of cytochrome c oxidase.

  2. Cerebral sinus venous thrombosis

    PubMed Central

    Alvis-Miranda, Hernando Raphael; Milena Castellar-Leones, Sandra; Alcala-Cerra, Gabriel; Rafael Moscote-Salazar, Luis

    2013-01-01

    Cerebral sinus venous thrombosis (CSVT) is a rare phenomenon that can be seen with some frequency in young patients. CSVT is a multifactorial condition with gender-related specific causes, with a wide clinical presentation, the leading causes differ between developed and developing countries, converting CSVT in a condition characterized by a highly variable clinical spectra, difficult diagnosis, variable etiologies and prognosis that requires fine medical skills and a high suspicious index. Patients who presents with CSVT should underwent to CT-scan venography (CVT) and to the proper inquiry of the generating cause. This disease can affect the cerebral venous drainage and related anatomical structure. The symptoms may appear in relation to increased intracranial pressure imitating a pseudotumorcerebri. Prognosis depends on the early detection. Correcting the cause, generally the complications can be prevented. Mortality trends have diminished, and with the new technologies, surely it will continue. This work aims to review current knowledge about CSVT including its pathogenesis, etiology, clinical manifestations, diagnosis, and treatment. PMID:24347950

  3. Cytochrome c Negatively Regulates NLRP3 Inflammasomes

    PubMed Central

    Shi, Chong-Shan; Kehrl, John H.

    2016-01-01

    The release of cytochrome c from the inner mitochondrial membrane, where it is anchored by caridolipin, triggers the formation of the Apaf-1 apoptosome. Cardiolipin also interacts with NLRP3 recruiting NLRP3 to mitochondria and facilitating inflammasome assembly. In this study we investigated whether cytosolic cytochrome c impacts NLRP3 inflammasome activation in macrophages. We report that cytochrome c binds to the LRR domain of NLRP3 and that cytochrome c reduces the interactions between NLRP3 and cardiolipin and between NLRP3 and NEK7, a recently recognized component of the NLRP3 inflammasome needed for NLRP3 oligomerization. Protein transduction of cytochrome c impairs NLRP3 inflammasome activation, while partially silencing cytochrome c expression enhances it. The addition of cytochrome c to an in vitro inflammasome assay severely limited caspase-1 activation. We propose that there is a crosstalk between the NLRP3 inflammasome and apoptosome pathways mediated by cytochrome c, whose release during apoptosis acts to limit NLRP3 inflammasome activation. PMID:28030552

  4. Idiopathic reversible cerebral vasoconstriction syndrome (RCVS).

    PubMed

    Abkur, Tarig Mohammed; Saeed, Mamoun; Alfaki, Nidal Osman; O'Connor, Margaret

    2014-10-15

    Reversible cerebral vasoconstriction syndrome is characterised by severe thunderclap headache with associated characteristic transient, multifocal, segmental vasoconstriction of cerebral arteries lasting several weeks to months. We describe a 50-years old woman who presented with a severe sudden onset occipital headache. Neuroimaging revealed segmental vasospasm affecting the intracerebral arteries. The pain improved gradually over the next 6 weeks. Repeat brain MR angiography at 12 weeks showed complete resolution of the segmental narrowing. 2014 BMJ Publishing Group Ltd.

  5. United Cerebral Palsy

    MedlinePlus

    ... stay up to date with everything UCP! Affiliate Network UCP affiliates provide services and support on a ... with Cerebral Palsy and other disabilities and their networks. Individuals with cerebral palsy and other disabilities deserve ...

  6. Cerebral Palsy (For Kids)

    MedlinePlus

    ... Emergency Room? What Happens in the Operating Room? Cerebral Palsy KidsHealth > For Kids > Cerebral Palsy A A A ... the things that kids do every day. What's CP? Some kids with CP use wheelchairs and others ...

  7. Outer-membrane cytochrome-c, OmcF from Geobacter sulfurreducens: high structural similarity to an algal cytochrome c6.

    SciTech Connect

    Pokkuluri, P. R.; Londer, Y. Y.; Wood, S. J.; Duke, N. E. C.; Morgado, L.; Salgueiro, C. A.; Schiffer, M.; Biosciences Division; Univ. Nova de Lisboa

    2009-01-01

    Putative outer membrane c-type cytochromes have been implicated in metal ion reducing properties of Geobacter sulfurreducens. OmcF (GSU2432), OmcB (GSU2731), and OmcC (GSU2737) are three such proteins that have predicted lipid anchors. OmcF is a monoheme cytochrome, whereas OmcB and OmcC are multiheme cytochromes. Deletion of OmcF was reported to affect the expression of OmcB and OmcC in G. sulfurreducens. The OmcF deficient strain was impaired in its ability to both reduce and grow on Fe(III) citrate probably because the expression of OmcB, which is crucial for iron reduction, is low in this strain. U(VI) reduction activity of this bacterium is also lower on deletion of OmcB or OmcF. The U(VI) reduction activity is affected more by the deletion of OmcF than by the deletion of OmcB. The soluble part of OmcF (residues 20-104, referred to as OmcF{sub S} hereafter) has sequence similarity to soluble cytochromes c{sub 6} of photosynthetic algae and cyanobacteria. The cytochrome c{sub 6} proteins in algae and cyanobacteria are electron transport proteins that mediate the transfer of electrons from cytochrome b{sub 6}f to photosystem I and have high reduction potentials of about +350 mV and low pI. The structures of seven cytochromes c{sub 6} have been previously determined. Further, a c{sub 6}-like cytochrome (PetJ2) of unknown function was recently identified in Synechoccus sp. PCC 7002 with a reduction potential of +148 mV and high pI. Here, we report the structure of OmcF{sub S} and its remarkable structural similarity to that of cytochrome c{sub 6} from the green alga, Monoraphidium braunii. To our knowledge, OmcF{sub S} is the first example of a cytochrome c{sub 6}-like structure from a nonphotosynthetic organism.

  8. Amino acid sequences of bacterial cytochromes c' and c-556.

    PubMed Central

    Ambler, R P; Bartsch, R G; Daniel, M; Kamen, M D; McLellan, L; Meyer, T E; Van Beeumen, J

    1981-01-01

    The cytochrome c' are electron transport proteins widely distributed in photosynthetic and aerobic bacteria. We report the amino acid sequences of the proteins from 12 different bacterial species, and we show by sequences that the cytochromes c-556 from 2 different bacteria are structurally related to the cytochromes c'. Unlike the mitochondrial cytochromes c, the heme binding site in the cytochromes c' and c-556 is near the COOH terminus. The cytochromes c-556 probably have a methionine sixth heme ligand located near the NH2 terminus, whereas the cytochromes c' may be pentacoordinate. Quantitative comparison of cytochrome c' and c-556 sequences indicates a relatively low 28% average identity. PMID:6273892

  9. Cerebral Palsy (For Kids)

    MedlinePlus

    ... CPR: A Real Lifesaver Kids Talk About: Coaches Cerebral Palsy KidsHealth > For Kids > Cerebral Palsy Print A A A What's in this article? ... the first word you spoke? For kids with cerebral palsy, called CP for short, taking a first step ...

  10. Aging and Cerebral Palsy.

    ERIC Educational Resources Information Center

    Networker, 1993

    1993-01-01

    This special edition of "The Networker" contains several articles focusing on aging and cerebral palsy (CP). "Aging and Cerebral Palsy: Pathways to Successful Aging" (Jenny C. Overeynder) reports on the National Invitational Colloquium on Aging and Cerebral Palsy held in April 1993. "Observations from an Observer" (Kathleen K. Barrett) describes…

  11. Effect of ageing and ischemia on enzymatic activities linked to Krebs' cycle, electron transfer chain, glutamate and aminoacids metabolism of free and intrasynaptic mitochondria of cerebral cortex.

    PubMed

    Villa, Roberto Federico; Gorini, Antonella; Hoyer, Siegfried

    2009-12-01

    The effect of ageing and the relationships between the catalytic properties of enzymes linked to Krebs' cycle, electron transfer chain, glutamate and aminoacid metabolism of cerebral cortex, a functional area very sensitive to both age and ischemia, were studied on mitochondria of adult and aged rats, after complete ischemia of 15 minutes duration. The maximum rate (Vmax) of the following enzyme activities: citrate synthase, malate dehydrogenase, succinate dehydrogenase for Krebs' cycle; NADH-cytochrome c reductase as total (integrated activity of Complex I-III), rotenone sensitive (Complex I) and cytochrome oxidase (Complex IV) for electron transfer chain; glutamate dehydrogenase, glutamate-oxaloacetate-and glutamate-pyruvate transaminases for glutamate metabolism were assayed in non-synaptic, perikaryal mitochondria and in two populations of intra-synaptic mitochondria, i.e., the light and heavy mitochondrial fraction. The results indicate that in normal, steady-state cerebral cortex, the value of the same enzyme activity markedly differs according (a) to the different populations of mitochondria, i.e., non-synaptic or intra-synaptic light and heavy, (b) and respect to ageing. After 15 min of complete ischemia, the enzyme activities of mitochondria located near the nucleus (perikaryal mitochondria) and in synaptic structures (intra-synaptic mitochondria) of the cerebral tissue were substantially modified by ischemia. Non-synaptic mitochondria seem to be more affected by ischemia in adult and particularly in aged animals than the intra-synaptic light and heavy mitochondria. The observed modifications in enzyme activities reflect the metabolic state of the tissue at each specific experimental condition, as shown by comparative evaluation with respect to the content of energy-linked metabolites and substrates. The derangements in enzyme activities due to ischemia is greater in aged than in adult animals and especially the non-synaptic and the intra-synaptic light

  12. Repeated Estradiol Treatment Attenuates Chronic Cerebral Hypoperfusion-Induced Neurodegeneration in Rat Hippocampus.

    PubMed

    Stanojlović, Miloš; Guševac, Ivana; Grković, Ivana; Mitrović, Nataša; Zlatković, Jelena; Horvat, Anica; Drakulić, Dunja

    2016-08-01

    Although a substantial number of pre-clinical and experimental studies have investigated effects of 17β-estradiol, its precise molecular mechanism of action in the early state of chronic cerebral hypoperfusion remains controversial. The present study attempted to verify whether post-ischemic estradiol treatment (33.3 μg/kg for seven consecutive days) affects previously reported number of hippocampal apoptotic cells and amount of DNA fragmentation characteristic for apoptosis as well as the expression of key elements within synaptosomal Akt and Erk signal transduction pathways (NF-κB, Bax, Bcl-2, cytochrome C, caspase 3, and PARP). Additionally, alterations of aforementioned molecules linked to protection in various neurodegenerative disorders were monitored in the cytosolic, mitochondrial, and nuclear fractions associating investigated kinases and NF-κB with gene expression of their downstream effectors-Bcl-2, Bax, and caspase 3. The results revealed that an initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by chronic cerebral hypoperfusion was significantly reduced by 17β-estradiol. In synaptic regions, an altered profile with respect to the protein expression of Bcl-2 and phosphorylated Akt was detected, although the level of other examined proteins was not modified. In other investigated sub-cellular fractions, 17β-estradiol elicited phosphorylation and translocation of Akt and Erk along with modulation of the expression of their subsequent effectors. Our findings support the concept that repeated post-ischemic 17β-estradiol treatment attenuates neurodegeneration induced by chronic cerebral hypoperfusion in hippocampus through the activation of investigated kinases and regulation of their downstream molecules in sub-cellular manner indicating a time window and regime of its administration as a valid therapeutic intervention.

  13. Simultaneous near-IR spectroscopy and magnetic resonance imaging to assess cerebral oxygenation and brain water during hypoxia-ischemia in two-week-old rats

    NASA Astrophysics Data System (ADS)

    Shaw, R. A.; Tuor, U. I.; Foniok, T.; Bascaramurty, S.; Ringland, K.; McKenzie, E.; Qiao, M.; Tomanek, B.; Mantsch, Henry H.

    2001-10-01

    Cerebral near-infrared spectroscopy can potentially probe several parameters related to the onset of stroke and the ensuing tissue damage. One obvious marker of ischemia is cerebral oxygenation, which can be lowered sharply in stroke-affected tissue. Also commonly assessed, though less straightforward to recover, is the redox state of the cytochrome aa3 copper center. Finally, parameters that are in principle available but seldom recovered from in vivo near-IR spectra are changes in water concentration and scattering properties of the tissue. We have evaluated the potential for near-IR spectroscopy to detect relevant changes in cerebral oxygenation, blood volume, water content, and scattering properties in an infant rat stroke model that is well characterized by magnetic resonance imaging methods. The specific aim was to acquire near-IR spectra simultaneously with MR images and to correlate stroke-associated changes detected via these two modalities prior to, during and after a hypoxia-ischemia episode within this stroke model. Presented here are results from the design and testing of a near-IR illumination/detection system that is compatible with an MR imaging system, and the recovery of trends in the near-IR spectra that complement the hypoxic-ischemic changes observed in the MR images. Unexpectedly large intensity changes observed for the in vivo near-IR water absorptions are ascribed to hypoxia-induced variations in effective optical pathlength, suggesting that the water absorptions may prove generally useful as a means to track such changes.

  14. Maturation of Plastid c-type Cytochromes.

    PubMed

    Gabilly, Stéphane T; Hamel, Patrice P

    2017-01-01

    Cytochromes c are hemoproteins, with the prosthetic group covalently linked to the apoprotein, which function as electron carriers. A class of cytochromes c is defined by a CXXCH heme-binding motif where the cysteines form thioether bonds with the vinyl groups of heme. Plastids are known to contain up to three cytochromes c. The membrane-bound cytochrome f and soluble cytochrome c6 operate in photosynthesis while the activity of soluble cytochrome c6A remains unknown. Conversion of apo- to holocytochrome c occurs in the thylakoid lumen and requires the independent transport of apocytochrome and heme across the thylakoid membrane followed by the stereospecific attachment of ferroheme via thioether linkages. Attachment of heme to apoforms of plastid cytochromes c is dependent upon the products of the CCS (for cytochrome csynthesis) genes, first uncovered via genetic analysis of photosynthetic deficient mutants in the green alga Chlamydomonas reinhardtii. The CCS pathway also occurs in cyanobacteria and several bacteria. CcsA and CCS1, the signature components of the CCS pathway are polytopic membrane proteins proposed to operate in the delivery of heme from the stroma to the lumen, and also in the catalysis of the heme ligation reaction. CCDA, CCS4, and CCS5 are components of trans-thylakoid pathways that deliver reducing equivalents in order to maintain the heme-binding cysteines in a reduced form prior to thioether bond formation. While only four CCS components are needed in bacteria, at least eight components are required for plastid cytochrome c assembly, suggesting the biochemistry of thioether formation is more nuanced in the plastid system.

  15. Multi-modal assessment of neurovascular coupling during cerebral ischaemia and reperfusion using remote middle cerebral artery occlusion.

    PubMed

    Sutherland, Brad A; Fordsmann, Jonas C; Martin, Chris; Neuhaus, Ain A; Witgen, Brent M; Piilgaard, Henning; Lønstrup, Micael; Couch, Yvonne; Sibson, Nicola R; Lauritzen, Martin; Buchan, Alastair M

    2017-07-01

    Hyperacute changes in cerebral blood flow during cerebral ischaemia and reperfusion are important determinants of injury. Cerebral blood flow is regulated by neurovascular coupling, and disruption of neurovascular coupling contributes to brain plasticity and repair problems. However, it is unknown how neurovascular coupling is affected hyperacutely during cerebral ischaemia and reperfusion. We have developed a remote middle cerebral artery occlusion model in the rat, which enables multi-modal assessment of neurovascular coupling immediately prior to, during and immediately following reperfusion. Male Wistar rats were subjected to remote middle cerebral artery occlusion, where a long filament was advanced intraluminally through a guide cannula in the common carotid artery. Transcallosal stimulation evoked increases in blood flow, tissue oxygenation and neuronal activity, which were diminished by middle cerebral artery occlusion and partially restored during reperfusion. These evoked responses were not affected by administration of the thrombolytic alteplase at clinically used doses. Evoked cerebral blood flow responses were fully restored at 24 h post-middle cerebral artery occlusion indicating that neurovascular dysfunction was not sustained. These data show for the first time that the rat remote middle cerebral artery occlusion model coupled with transcallosal stimulation provides a novel method for continuous assessment of hyperacute neurovascular coupling changes during ischaemia and reperfusion, and offers unique insight into hyperacute ischaemic pathophysiology.

  16. A world of cytochrome P450s.

    PubMed

    Nelson, David R

    2013-02-19

    The world we live in is a biosphere influenced by all organisms who inhabit it. It is also an ecology of genes, with some having rather startling effects. The premise put forth in this issue is cytochrome P450 is a significant player in the world around us. Life and the Earth itself would be visibly different and diminished without cytochrome P450s. The contributions to this issue range from evolution on the billion year scale to the colour of roses, from Darwin to Rachel Carson; all as seen through the lens of cytochrome P450.

  17. Contrasting pediatric and adult cerebral malaria

    PubMed Central

    Hawkes, Michael; Elphinstone, Robyn E; Conroy, Andrea L; Kain, Kevin C

    2013-01-01

    Malaria affects millions of people around the world and a small subset of those infected develop cerebral malaria. The clinical presentation of cerebral malaria differs between children and adults, and it has been suggested that age-related changes in the endothelial response may account for some of these differences. During cerebral malaria, parasites sequester within the brain microvasculature but do not penetrate into the brain parenchyma and yet, the infection causes severe neurological symptoms. Endothelial dysfunction is thought to play an important role in mediating these adverse clinical outcomes. During infection, the endothelium becomes activated and more permeable, which leads to increased inflammation, hemorrhages, and edema in the surrounding tissue. We hypothesize that post-natal developmental changes, occurring in both endothelial response and the neurovascular unit, account for the differences observed in the clinical presentations of cerebral malaria in children compared with adults. PMID:23924893

  18. Reversible cerebral vasoconstriction syndrome: a comprehensive update.

    PubMed

    Mehdi, Ali; Hajj-Ali, Rula A

    2014-09-01

    Reversible cerebral vasoconstriction syndrome (RCVS) is a clinico-radiological syndrome characterized by recurrent thunderclap headache, with or without neurologic symptoms, and reversible vasoconstriction of cerebral arteries. RCVS affects patients in various racial and ethnic groups and in all age groups, although most commonly in the fourth decade of life. Many conditions and exposures have been linked to RCVS, including vasoactive drugs and the peripartum period. Disturbance of the cerebral vascular tone is thought to contribute to the disease's pathophysiology. RCVS generally follows a monophasic course. Associated strokes and cerebral hemorrhages are not uncommon. In this review we will attempt to provide a comprehensive overview of RCVS, with emphasis on the controversies in the field and the newest findings in the reported literature.

  19. Acute cerebral vasculopathy in systemic sclerosis.

    PubMed

    Faucher, Benoit; Granel, Brigitte; Nicoli, Francois

    2013-12-01

    Systemic sclerosis is an autoimmune disease characterized by skin and deep organ fibrosis and obliterative microvasculopathy. Cerebral involvement is currently not recognized as a manifestation of the disease, although several morphologic and functional studies suggested a frequent cerebral involvement in systemic sclerosis. We report a new case of acute cerebral vasculopathy in a patient suffering from systemic sclerosis together with five historical cases identified through a literature review. Cerebral acute vasculopathy most often revealed the disease. Affected patients suffered often from limited or diffuse cutaneous systemic sclerosis. Reversibility of arterial lesions, absence of specific histologic findings, and association with severe peripheral vascular involvement plead for a major role of vasospasm. However, the apparent efficacy of immunosuppressive treatments suggests an association with inflammatory or immune mechanisms. Awareness should be raised because of the severity of the disease, the risk of relapse, and the possible occurrence early in the course of systemic sclerosis.

  20. Bcr-Abl-Mediated Protection from Apoptosis Downstream of Mitochondrial Cytochrome c Release

    PubMed Central

    Deming, Paula B.; Schafer, Zachary T.; Tashker, Jessica S.; Potts, Malia B.; Deshmukh, Mohanish; Kornbluth, Sally

    2004-01-01

    Bcr-Abl, activated in chronic myelogenous leukemias, is a potent cell death inhibitor. Previous reports have shown that Bcr-Abl prevents apoptosis through inhibition of mitochondrial cytochrome c release. We report here that Bcr-Abl also inhibits caspase activation after the release of cytochrome c. Bcr-Abl inhibited caspase activation by cytochrome c added to cell-free lysates and prevented apoptosis when cytochrome c was microinjected into intact cells. Bcr-Abl acted posttranslationally to prevent the cytochrome c-induced binding of Apaf-1 to procaspase 9. Although Bcr-Abl prevented interaction of endogenous Apaf-1 with the recombinant prodomain of caspase 9, it did not affect the association of endogenous caspase 9 with the isolated Apaf-1 caspase recruitment domain (CARD) or Apaf-1 lacking WD-40 repeats. These data suggest that Apaf-1 recruitment of caspase 9 is faulty in the presence of Bcr-Abl and that cytochrome c/dATP-induced exposure of the Apaf-1 CARD is likely defective. These data provide a novel locus of Bcr-Abl antiapoptotic action and suggest a distinct mechanism of apoptosomal inhibition. PMID:15542838

  1. Inactivation of nitric oxide by cytochrome c oxidase under steady-state oxygen conditions.

    PubMed

    Unitt, David C; Hollis, Veronica S; Palacios-Callender, Miriam; Frakich, Nanci; Moncada, Salvador

    2010-03-01

    We have developed a respiration chamber that allows intact cells to be studied under controlled oxygen (O(2)) conditions. The system measures the concentrations of O(2) and nitric oxide (NO) in the cell suspension, while the redox state of cytochrome c oxidase is continuously monitored optically. Using human embryonic kidney cells transfected with a tetracycline-inducible NO synthase we show that the inactivation of NO by cytochrome c oxidase is dependent on both O(2) concentration and electron turnover of the enzyme. At a high O(2) concentration (70 microM), and while the enzyme is in turnover, NO generated by the NO synthase upon addition of a given concentration of l-arginine is partially inactivated by cytochrome c oxidase and does not affect the redox state of the enzyme or consumption of O(2). At low O(2) (15 microM), when the cytochrome c oxidase is more reduced, inactivation of NO is decreased. In addition, the NO that is not inactivated inhibits the cytochrome c oxidase, further reducing the enzyme and lowering O(2) consumption. At both high and low O(2) concentrations the inactivation of NO is decreased when sodium azide is used to inhibit cytochrome c oxidase and decrease electron turnover.

  2. Toxic dark effects of protoporphyrin on the cytochrome P-450 system in rat liver microsomes.

    PubMed Central

    Williams, M; Van der Zee, J; Van Steveninck, J

    1992-01-01

    In erythropoietic protoporphyria, accumulation of protoporphyrin has been found in various tissues and liver cirrhosis occurs frequently in this disease, probably due to toxic dark effects of protoporphyrin. We have studied the effect of porphyrins on various enzymic functions in rat liver microsomes. Incubation of microsomes with protoporphyrin resulted in a concentration-dependent inhibition of the oxidation of 7-ethoxycoumarin and aminopyrine by the cytochrome P-450 system. Kinetic analysis showed a decrease in Vmax., whereas the Km was not affected (non-competitive inhibition). Furthermore, reduction of cytochrome c by the NADPH-cytochrome P-450 reductase and by the NADH-cytochrome b5 reductase was inhibited. However, the activity of the reductases was only affected when the microsomes were pre-incubated with protoporphyrin, and it was found that the inhibition was dependent on the duration of the pre-incubation. Kinetic analysis again revealed non-competitive inhibition. When these experiments were repeated with uroporphyrin, no inhibition could be observed. With Stern-Volmer plots it was demonstrated that this was most likely caused by the localization of the porphyrins: protoporphyrin is localized in the membrane, whereas uroporphyrin remains in solution. From these results it is concluded that accumulation of protoporphyrin in the liver may markedly affect the cytochrome P-450 system and thus its detoxification function. PMID:1332695

  3. The Interaction of Microsomal Cytochrome P450 2B4 with its Redox Partners, Cytochrome P450 Reductase and Cytochrome b5

    PubMed Central

    Im, Sang-Choul; Waskell, Lucy

    2010-01-01

    1 Cytochrome P450 2B4 is a microsomal protein with a multi-step reaction cycle similar to that observed in the majority of other cytochromes P450. The cytochrome P450 2B4-substrate complex is reduced from the ferric to the ferrous form by cytochrome P450 reductase. After binding oxygen, the oxyferrous protein accepts a second electron which is provided by either cytochrome P450 reductase or cytochrome b5. In both instances, product formation occurs. When the second electron is donated by cytochrome b5, catalysis (product formation) is ∼ 10 to 100-fold faster than in the presence of cytochrome P450 reductase. This allows less time for side product formation (hydrogen peroxide and superoxide) and improves by ∼ 15% the coupling of NADPH consumption to product formation. Cytochrome b5 has also been shown to compete with cytochrome P450 reductase for a binding site on the proximal surface of cytochrome P450 2B4. These two different effects of cytochrome b5 on cytochrome P450 2B4 reactivity can explain how cytochrome b5 is able to stimulate, inhibit, or have no effect on cytochrome P450 2B4 activity. At low molar ratios (<1) of cytochrome b5 to cytochrome P450 reductase, the more rapid catalysis results in enhanced substrate metabolism. In contrast, at high molar ratios (>1) of cytochome b5 to cytochrome P450 reductase, cytochrome b5 inhibits activity by binding to the proximal surface of cytochrome P450 and preventing the reductase from reducing ferric cytochrome P450 to the ferrous protein, thereby aborting the catalytic reaction cycle. When the stimulatory and inhibitory effects of cytochrome b5 are equal, it will appear to have no effect on the enzymatic activity. It is hypothesized that cytochrome b5 stimulates catalysis by causing a conformational change in the active site, which allows the active oxidizing oxyferryl species of cytochrome P450 to be formed more rapidly than in the presence of reductase. PMID:21055385

  4. Cytochromes P460 and c'-beta; a new family of high-spin cytochromes c.

    PubMed

    Elmore, Bradley O; Bergmann, David J; Klotz, Martin G; Hooper, Alan B

    2007-03-06

    Cytochromes-P460 of Nitrosomonas europaea and Methylococcus capsulatus (Bath), and the cytochrome c' of M. capsulatus, believed to be involved in binding or transformation of N-oxides, are shown to represent an evolutionarily related new family of monoheme, approximately 17kDa, cytochromes c found in the genomes of diverse Proteobacteria. All members of this family have a predicted secondary structure predominantly of beta-sheets in contrast to the predominantly alpha-helical cytochromes c' found in photoheterotrophic and denitrifying Proteobacteria.

  5. Mutations in the membrane anchor of yeast cytochrome c1 compensate for the absence of Oxa1p and generate carbonate-extractable forms of cytochrome c1.

    PubMed Central

    Hamel, P; Lemaire, C; Bonnefoy, N; Brivet-Chevillotte, P; Dujardin, G

    1998-01-01

    Oxa1p is a mitochondrial inner membrane protein that is mainly required for the insertion/assembly of complex IV and ATP synthase and is functionally conserved in yeasts, humans, and plants. We have isolated several independent suppressors that compensate for the absence of Oxa1p. Molecular cloning and sequencing reveal that the suppressor mutations (CYT1-1 to -6) correspond to amino acid substitutions that are all located in the membrane anchor of cytochrome c1 and decrease the hydrophobicity of this anchor. Cytochrome c1 is a catalytic subunit of complex III, but the CYT1-1 mutation does not seem to affect the electron transfer activity. The double-mutant cyt1-1,164, which has a drastically reduced electron transfer activity, still retains the suppressor activity. Altogether, these results suggest that the suppressor function of cytochrome c1 is independent of its electron transfer activity. In addition to the membrane-bound cytochrome c1, carbonate-extractable forms accumulate in all the suppressor strains. We propose that these carbonate-extractable forms of cytochrome c1 are responsible for the suppressor function by preventing the degradation of the respiratory complex subunits that occur in the absence of Oxa1p. PMID:9755193

  6. Effect of naphthalene on cytochrome oxidase activity

    SciTech Connect

    Harmon, H.J.

    1988-01-01

    Previous reports have demonstrated that naphthalene inhibits oxygen consumption in Daphnia magna tissue culture cells, and intact mitochondria and submitochondrial particles. These studies were extended to algal mitochondrial respiration as well as photosynthetic activity. The authors were able to demonstrate the specific site of apparent respiratory inhibition to be coenzyme Q (ubiquinone, UQ) and later to demonstrate the molecular basis of this inhibition at ubiquinone. The authors previously could not demonstrate an effect of naphthalene on cytochrome oxidase activity. However, the observation that naphthalene can stimulate respiration in algae prompted the reinvestigation of the effect of naphthalene on the kinetics of cytochrome oxidase. Cytochrome oxidase is a multi-subunit membranous protein responsible for the oxidation of cytochrome c and the reduction of molecular oxygen to water. Because of the complicated nature and mechanism of this enzyme, the potential exists for multiple and possibly opposite effects of naphthalene on its function.

  7. Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

    PubMed Central

    Berghella, Libera; Ferraro, Elisabetta

    2012-01-01

    Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

  8. Kienböck's disease in cerebral palsy.

    PubMed

    Leclercq, C; Xarchas, C

    1998-12-01

    The incidence of Kienböck's disease is known to be higher in cerebral palsy patients, but little has been written on treatment. We report a case of Kienböck's disease in a young man affected by cerebral palsy. A proximal row carpectomy was done, which relieved spasticity at the same time as treating the disease.

  9. How Abnormal Reflexes Influence Movements in Cerebral Palsy.

    ERIC Educational Resources Information Center

    Sellers, Jeanne Shanks

    Some of the more frequently observed reflex patterns in cerebral palsy are examined, and descriptions are given of how they affect movement. A chart outlines: (1) desirable movement patterns; (2) typical abnormal movement of the cerebral palsied child; (3) possible physical cause of abnormal movements; and (4) activities which may facilitate…

  10. Metazoan cytochrome P450 evolution.

    PubMed

    Nelson, D R

    1998-11-01

    There are 37 cytochrome P450 families currently identified in animals. The concept of higher order groupings of P450 families called P450 CLANS is introduced. The mammalian CYP3 and CYP5 families belong to the same clan as insect CYP6 and CYP9. All mitochondrial P450s seem to belong to the same clan. Lack of mitochondrial P450s in C. elegans suggests that mitochondrial P450s probably arose from the mistargeting of a microsomal P450 after the coelomates diverged from acoelomates and pseudocoelomates. Different taxonomic groups appear to have recruited different ancestral P450s for expansion as they evolved, since each major taxon seems to have one large cluster of P450s. In insects, this cluster derives from the ancestor to the CYP4 family. Vertebrates and C. elegans may have used the same ancestor independently to generate the CYP1, 2, 17, and 21 families in vertebrates and a large distinctive clan with 45 genes in C. elegans.

  11. Cytochrome bd Displays Significant Quinol Peroxidase Activity

    PubMed Central

    Al-Attar, Sinan; Yu, Yuanjie; Pinkse, Martijn; Hoeser, Jo; Friedrich, Thorsten; Bald, Dirk; de Vries, Simon

    2016-01-01

    Cytochrome bd is a prokaryotic terminal oxidase that catalyses the electrogenic reduction of oxygen to water using ubiquinol as electron donor. Cytochrome bd is a tri-haem integral membrane enzyme carrying a low-spin haem b558, and two high-spin haems: b595 and d. Here we show that besides its oxidase activity, cytochrome bd from Escherichia coli is a genuine quinol peroxidase (QPO) that reduces hydrogen peroxide to water. The highly active and pure enzyme preparation used in this study did not display the catalase activity recently reported for E. coli cytochrome bd. To our knowledge, cytochrome bd is the first membrane-bound quinol peroxidase detected in E. coli. The observation that cytochrome bd is a quinol peroxidase, can provide a biochemical basis for its role in detoxification of hydrogen peroxide and may explain the frequent findings reported in the literature that indicate increased sensitivity to hydrogen peroxide and decreased virulence in mutants that lack the enzyme. PMID:27279363

  12. [Reversible cerebral vasoconstriction syndrome].

    PubMed

    Laakso, Elina; Pekkola, Johanna; Soinne, Lauri; Putaala, Jukka

    2014-01-01

    Reversible cerebral vasoconstriction syndrome (RCVS) is increasingly recognized. The condition is characterized by multifocal vasoconstriction lesions in cerebral arteries. Headache is the central symptom, with an acute onset and paroxysmal occurrence. Some of the patients develop intracranial hemorrhage, ischemic disturbance of the cerebral circulation, hypertensive encephalopathy (PRES) or epileptic seizures as complications. The disease is most common in middle-aged women. Most patients have an underlying predisposing factor, most commonly vasoactive medications, drugs or puerperium. There is no evidence-based practice.

  13. Statins and cerebral hemodynamics

    PubMed Central

    Giannopoulos, Sotirios; Katsanos, Aristeidis H; Tsivgoulis, Georgios; Marshall, Randolph S

    2012-01-01

    HMG-CoA reductase inhibitors (statins) are associated with improved stroke outcome. This observation has been attributed in part to the palliative effect of statins on cerebral hemodynamics and cerebral autoregulation (CA), which are mediated mainly through the upregulation of endothelium nitric oxide synthase (eNOS). Several animal studies indicate that statin pretreatment enhances cerebral blood flow after ischemic stroke, although this finding is not further supported in clinical settings. Cerebral vasomotor reactivity, however, is significantly improved after long-term statin administration in most patients with severe small vessel disease, aneurysmal subarachnoid hemorrhage, or impaired baseline CA. PMID:22929438

  14. Kinetics of flavin semiquinone reduction of the components of the cytochrome c-cytochrome b5 complex.

    PubMed

    Eltis, L; Mauk, A G; Hazzard, J T; Cusanovich, M A; Tollin, G

    1988-07-26

    The kinetics of flavin semiquinone reduction of the components of the 1:1 complex formed by cytochrome c with either cytochrome b5 or a derivative of cytochrome b5 in which the heme propionates are esterified (DME-cytochrome b5) have been studied. The rate constant for the reduction of horse heart cytochrome c by the electrostatically neutral lumiflavin semiquinone (LfH) is unaffected by complexation with native cytochrome b5 at pH 7. However, complex formation with DME-cytochrome b5 (pH 7) decreases by 35% the rate constant for cytochrome c reduction by LfH. At pH 8, complex formation with native cytochrome b5 decreases the rate constant for cytochrome c reduction by LfH markedly, whereas the rate constant for cytochrome c reduction, either unbound or in the complex formed with DME-cytochrome b5, is increased 2-fold relative to pH 7. These results indicate that the accessibility of the cytochrome c heme is not the same in the complexes formed with the two cytochrome b5 derivatives and that the docking geometry of the complex formed by the two native cytochromes is pH dependent. Binding of horse heart and tuna cytochromes c to native and DME-cytochromes b5 decreases the rate constants for reduction of cytochrome c by the negatively charged flavin mononucleotide semiquinone (FMNH) by approximately 30% and approximately 40%, respectively. This finding is attributed to substantial neutralization of the positive electrostatic potential surface of cytochrome c that occurs when it binds to either form of cytochrome b5.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. [Posterior cerebral artery infarctions with possible interaction between hypoperfusion and embolism].

    PubMed

    Durand-Birchenall, J; Bugnicourt, J-M

    2013-12-01

    Although embolism and hypoperfusion may well occur concurrently in a non-negligible proportion of cerebral infarction patients, there is currently lack of proof, especially in the posterior circulation. Here, we are reporting on a case of multiple cerebral infarctions in a patient with neurofibromatosis type 1, multiple vascular abnormalities of the posterior cerebral circulation and intracranial artery occlusion. We hypothesize that cerebral blood flow impairment may have affected the clearance and destination of embolic particles.

  16. Cerebral blood flow variations in CNS lupus

    SciTech Connect

    Kushner, M.J.; Tobin, M.; Fazekas, F.; Chawluk, J.; Jamieson, D.; Freundlich, B.; Grenell, S.; Freemen, L.; Reivich, M. )

    1990-01-01

    We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery.

  17. Cytochrome c1 exhibits two binding sites for cytochrome c in plants.

    PubMed

    Moreno-Beltrán, Blas; Díaz-Quintana, Antonio; González-Arzola, Katiuska; Velázquez-Campoy, Adrián; De la Rosa, Miguel A; Díaz-Moreno, Irene

    2014-10-01

    In plants, channeling of cytochrome c molecules between complexes III and IV has been purported to shuttle electrons within the supercomplexes instead of carrying electrons by random diffusion across the intermembrane bulk phase. However, the mode plant cytochrome c behaves inside a supercomplex such as the respirasome, formed by complexes I, III and IV, remains obscure from a structural point of view. Here, we report ab-initio Brownian dynamics calculations and nuclear magnetic resonance-driven docking computations showing two binding sites for plant cytochrome c at the head soluble domain of plant cytochrome c1, namely a non-productive (or distal) site with a long heme-to-heme distance and a functional (or proximal) site with the two heme groups close enough as to allow electron transfer. As inferred from isothermal titration calorimetry experiments, the two binding sites exhibit different equilibrium dissociation constants, for both reduced and oxidized species, that are all within the micromolar range, thus revealing the transient nature of such a respiratory complex. Although the docking of cytochrome c at the distal site occurs at the interface between cytochrome c1 and the Rieske subunit, it is fully compatible with the complex III structure. In our model, the extra distal site in complex III could indeed facilitate the functional cytochrome c channeling towards complex IV by building a "floating boat bridge" of cytochrome c molecules (between complexes III and IV) in plant respirasome.

  18. The role of cytochrome b5 structural domains in interaction with cytochromes P450.

    PubMed

    Sergeev, G V; Gilep, A A; Usanov, S A

    2014-05-01

    To understand the role of the structural elements of cytochrome b5 in its interaction with cytochrome P450 and the catalysis performed by this heme protein, we carried out comparative structural and functional analysis of the two major mammalian forms of membrane-bound cytochrome b5 - microsomal and mitochondrial, designed chimeric forms of the heme proteins in which the hydrophilic domain of one heme protein is replaced by the hydrophilic domain of another one, and investigated the effect of the highly purified native and chimeric heme proteins on the enzymatic activity of recombinant cytochromes P4503A4 and P45017A1 (CYP3A4 and CYP17A1). We show that the presence of a hydrophobic domain in the structure of cytochrome b5 is necessary for its effective interaction with its redox partners, while the nature of the hydrophobic domain has no significant effect on the ability of cytochrome b5 to stimulate the activity of cytochrome P450-catalyzed reactions. Thus, the functional properties of cytochrome b5 are mainly determined by the structure of the heme-binding domain.

  19. Cytochrome P450 3A, NADPH cytochrome P450 reductase and cytochrome b5 in the upper airways in horse.

    PubMed

    Tydén, E; Olsén, L; Tallkvist, J; Tjälve, H; Larsson, P

    2008-08-01

    Gene and protein expression as well as catalytic activity of cytochrome P450 (CYP) 3A were studied in the nasal olfactory and respiratory mucosa and the tracheal mucosa of the horse. We also examined the activity of NADPH cytochrome P450 reductase (NADPH P450 reductase), the amount of cytochrome b(5) and the total CYP content in these tissues. Comparative values for the above were obtained using liver as a control. The CYP3A related catalytic activity in the tissues of the upper airways was considerably higher than in the liver. The CYP3A gene and protein expression, on the other hand, was higher in the liver than in the upper airway tissues. Thus, the pattern of CYP3A metabolic activity does not correlate with the CYP3A gene and protein expression. Our results showed that the activity of NADPH P450 reductase and the level of cytochrome b(5) in the relation to the gene and protein expression of CYP3A were higher in the tissues of the upper airways than in the liver. It is concluded that CYP3A related metabolism in horse is not solely dependent on the expression of the enzyme but also on adequate levels of NADPH P450 reductase and cytochrome b(5).

  20. Cerebral Asymmetries and Reading Acquisition

    ERIC Educational Resources Information Center

    Pirozzolo, Francis J.

    1978-01-01

    Reviewed are historical developments regarding the concepts of cerebral localization, and analyzed are implications of current research on the role of the cerebral hemispheres in reading disorders. (CL)

  1. The cytochrome bd respiratory oxygen reductases.

    PubMed

    Borisov, Vitaliy B; Gennis, Robert B; Hemp, James; Verkhovsky, Michael I

    2011-11-01

    Cytochrome bd is a respiratory quinol: O₂ oxidoreductase found in many prokaryotes, including a number of pathogens. The main bioenergetic function of the enzyme is the production of a proton motive force by the vectorial charge transfer of protons. The sequences of cytochromes bd are not homologous to those of the other respiratory oxygen reductases, i.e., the heme-copper oxygen reductases or alternative oxidases (AOX). Generally, cytochromes bd are noteworthy for their high affinity for O₂ and resistance to inhibition by cyanide. In E. coli, for example, cytochrome bd (specifically, cytochrome bd-I) is expressed under O₂-limited conditions. Among the members of the bd-family are the so-called cyanide-insensitive quinol oxidases (CIO) which often have a low content of the eponymous heme d but, instead, have heme b in place of heme d in at least a majority of the enzyme population. However, at this point, no sequence motif has been identified to distinguish cytochrome bd (with a stoichiometric complement of heme d) from an enzyme designated as CIO. Members of the bd-family can be subdivided into those which contain either a long or a short hydrophilic connection between transmembrane helices 6 and 7 in subunit I, designated as the Q-loop. However, it is not clear whether there is a functional consequence of this difference. This review summarizes current knowledge on the physiological functions, genetics, structural and catalytic properties of cytochromes bd. Included in this review are descriptions of the intermediates of the catalytic cycle, the proposed site for the reduction of O₂, evidence for a proton channel connecting this active site to the bacterial cytoplasm, and the molecular mechanism by which a membrane potential is generated. 2011 Elsevier B.V. All rights reserved.

  2. Cytochrome bc1 complexes of microorganisms.

    PubMed Central

    Trumpower, B L

    1990-01-01

    The cytochrome bc1 complex is the most widely occurring electron transfer complex capable of energy transduction. Cytochrome bc1 complexes are found in the plasma membranes of phylogenetically diverse photosynthetic and respiring bacteria, and in the inner mitochondrial membrane of all eucaryotic cells. In all of these species the bc1 complex transfers electrons from a low-potential quinol to a higher-potential c-type cytochrome and links this electron transfer to proton translocation. Most bacteria also possess alternative pathways of quinol oxidation capable of circumventing the bc1 complex, but these pathways generally lack the energy-transducing, protontranslocating activity of the bc1 complex. All cytochrome bc1 complexes contain three electron transfer proteins which contain four redox prosthetic groups. These are cytochrome b, which contains two b heme groups that differ in their optical and thermodynamic properties; cytochrome c1, which contains a covalently bound c-type heme; and a 2Fe-2S iron-sulfur protein. The mechanism which links proton translocation to electron transfer through these proteins is the proton motive Q cycle, and this mechanism appears to be universal to all bc1 complexes. Experimentation is currently focused on understanding selected structure-function relationships prerequisite for these redox proteins to participate in the Q-cycle mechanism. The cytochrome bc1 complexes of mitochondria differ from those of bacteria, in that the former contain six to eight supernumerary polypeptides, in addition to the three redox proteins common to bacteria and mitochondria. These extra polypeptides are encoded in the nucleus and do not contain redox prosthetic groups. The functions of the supernumerary polypeptides of the mitochondrial bc1 complexes are generally not known and are being actively explored by genetically manipulating these proteins in Saccharomyces cerevisiae. Images PMID:2163487

  3. The cytochrome bd respiratory oxygen reductases

    PubMed Central

    Borisov, Vitaliy B.; Gennis, Robert B.; Hemp, James; Verkhovsky, Michael I.

    2011-01-01

    Summary Cytochrome bd is a respiratory quinol:O2 oxidoreductase found in many prokaryotes, including a number of pathogens. The main bioenergetic function of the enzyme is the production of a proton motive force by the vectorial charge transfer of protons. The sequences of cytochromes bd are not homologous to those of the other respiratory oxygen reductases, i.e., the heme-copper oxygen reductases or alternative oxidases (AOX). Generally, cytochromes bd are noteworthy for their high affinity for O2 and resistance to inhibition by cyanide. In E. coli, for example, cytochrome bd (specifically, cytochrome bd-I) is expressed under O2-limited conditions. Among the members of the bd-family are the so-called cyanide-insensitive quinol oxidases (CIO) which often have a low content of the eponymous heme d but, instead, have heme b in place of heme d in at least a majority of the enzyme population. However, at this point, no sequence motif has been identified to distinguish cytochrome bd (with a stoichiometric complement of heme d) from an enzyme designated as CIO. Members of the bd-family can be subdivided into those which contain either a long or a short hydrophilic connection between transmembrane helices 6 and 7 in subunit I, designated as the Q-loop. However, it is not clear whether there is a functional consequence of this difference. This review summarizes current knowledge on the physiological functions, genetics, structural and catalytic properties of cytochromes bd. Included in this review are descriptions of the intermediates of the catalytic cycle, the proposed site for the reduction of O2, evidence for a proton channel connecting this active site to the bacterial cytoplasm, and the molecular mechanism by which a membrane potential is generated. PMID:21756872

  4. The small domain of cytochrome f from the psychrophile Chlamydomonas raudensis UWO 241 modulates the apparent molecular mass and decreases the accumulation of cytochrome f in the mesophile Chlamydomonas reinhardtii.

    PubMed

    Gudynaite-Savitch, Loreta; Loiselay, Christelle; Savitch, Leonid V; Simmonds, John; Kohalmi, Susanne E; Choquet, Yves; Hüner, Norman P A

    2007-10-01

    Cytochrome f from the psychrophile Chlamydomonas raudensis UWO 241 has a lower thermostability of its c-type heme and an apparent molecular mass that is 7 kDa lower than that of the model mesophilic green alga Chlamydomonas reinhardtii. We combined chloroplast transformation, site-directed mutagensis, and the creation of chimeric fusion constructs to assess the contribution of specific domains and (or) amino acids residues to the structure, stability, and accumulation of cytochrome f, as well as its function in photosynthetic intersystem electron transport. We demonstrate that differences in the amino acid sequence of the small domain and specific charged amino acids in the large domain of cytochrome f alter the physical properties of this protein but do not affect either the thermostability of the c-type heme, the apparent half-life of cytochrome f in the presence of the chloroplastic protein synthesis inhibitor chloramphenicol, or the capacity for photosynthetic intersystem electron transport, measured as e-/P700. However, pulse-labeling with [14C]acetate, combined with immunoblotting, indicated that the negative autoregulation of cytochrome f accumulation observed in mesophilic C. reinhardtii transformed with chimeric constructs from the psychrophile was likely the result of the defective association of the chimeric forms of cytochrome f with the other subunits of the cytochrome b6/f complex native to the C. reinhardtii wild type. These results are discussed in terms of the unique fatty acid composition of the thylakoid membranes of C. raudensis UWO 241 adapted to cold environments.

  5. The cytochromes in microsomal fractions of germinating mung beans.

    PubMed Central

    Hendry, G A; Houghton, J D; Jones, O T

    1981-01-01

    Detailed studies of microsomal cytochromes from mung-bean radicles showed the presence of cytochrome P-420, particularly in dark-grown seedlings, accompanied by smaller quantities of cytochrome P-450. Similar proportions of cytochrome P-420 to cytochrome P-450 were found spectrophotometrically in vivo with whole radicles and hypocotyls. Assayed in vitro, maximum concentrations of both cytochromes were attained after 4 days of growth, before undergoing rapid degradation. Illumination of seedlings stabilized cytochrome P-450 and decreased the amount of cytochrome P-420. Three b cytochromes were present in the microsomal fraction, namely cytochromes b-562.5 (Em + 105 +/- 23 mV), b-560.5 (Em + 49 +/- 13 mV) and b5 (Em - 45 +/- 14 mV), all at pH 7.0. Of the b cytochromes, cytochrome b5 alone undergoes a rapid degradation after day 4, Changes in cytochrome b concentrations were confined to the microsomal fraction: mitochondrial b cytochrome concentrations were unaltered with age. Protohaem degradation (of exogenous methaemalbumin) was detected in microsomal fractions of mung beans. The rates of degradation were highest in extracts of young tissue and declined after day 4. The degradation mechanism and products did not resemble those of mammalian haem oxygenase. PMID:7306021

  6. Schisandrin B enhances cerebral mitochondrial antioxidant status and structural integrity, and protects against cerebral ischemia/reperfusion injury in rats.

    PubMed

    Chen, Na; Chiu, Po Yee; Ko, Kam Ming

    2008-07-01

    Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to enhance mitochondrial antioxidant status in liver, heart and brain tissues in rodents. Whether or not long-term Sch B treatment can protect against oxidative stress-induced cerebral damage remains unclear. In the present study, the effect of long-term Sch B treatment (1-30 mg/kg/dx15) on cerebral ischemia/reperfusion (I/R) injury was examined in rats. Sch B treatment protected against I/R-induced cerebral damage, as evidenced by the significant increase in the percentage of 2,3,5-triphenyl tetrazolium chloride (TTC)-stained tissues in representative brain slices, when compared with the Sch B-untreated and I/R control. The cerebroprotection was associated with an enhancement in cerebral mitochondrial antioxidant status, as assessed by the level/activity of reduced glutathione, alpha-tocopherol and Mn-superoxide dismutase, as well as the improvement/preservation of mitochondrial structural integrity, as assessed by the extents of malondialdehyde production, Ca(2+) loading and cytochrome c release, as well as the sensitivity to Ca(2+)-induced permeability transition, in control and I/R-challenged rats. In conclusion, long-term Sch B treatment could enhance cerebral mitochondrial antioxidant status as well as improve mitochondrial structural integrity, thereby protecting against I/R injury.

  7. NADPH: cytochrome P-450 reductase in olfactory epithelium. Relevance to cytochrome P-450-dependent reactions.

    PubMed Central

    Reed, C J; Lock, E A; De Matteis, F

    1986-01-01

    The presence of a very active cytochrome P-450-dependent drug-metabolizing system in the olfactory epithelium has been confirmed by using 7-ethoxycoumarin, 7-ethoxyresorufin, hexobarbitone and aniline as substrates, and the reasons for the marked activity of the cytochrome P-450 in this tissue have been investigated. The spectral interaction of hexobarbitone and aniline with hepatic and olfactory microsomes has been examined. By this criterion there was no evidence for marked differences in the spin state of the cytochromes of the two tissues, or for the olfactory epithelium containing a greater amount of cytochrome capable of binding hexobarbitone, a very actively metabolized substrate. Rates of NADPH and NADH: cytochrome c reductase activity were found to be higher in the olfactory epithelium than in the liver, and direct evidence was obtained for a greater amount of the NADPH-dependent flavoprotein in the olfactory microsomes. Investigation of male rats and male and female mice, as well as male hamsters, demonstrated that, in all cases, the cytochrome P-450 levels of the olfactory epithelium were lower than those of the liver, while the 7-ethoxycoumarin de-ethylase and NADPH:cytochrome c reductase activities were higher. A correlation was found between 7-ethoxycoumarin de-ethylase and NADPH:cytochrome c reductase activities for both tissues in all species examined. The ratio of reductase to cytochrome P-450 was found to be considerably higher in the olfactory epithelium (1:2-1:3) than in the liver (1:11-1:15), regardless of the species examined, suggesting that facilitated electron flow may contribute significantly to the cytochrome P-450 catalytic turnover in the olfactory tissue. Images Fig. 1. PMID:3101674

  8. Bone age in cerebral palsy

    PubMed Central

    Miranda, Eduardo Régis de Alencar Bona; Palmieri, Maurício D'arc; de Assumpção, Rodrigo Montezuma César; Yamada, Helder Henzo; Rancan, Daniela Regina; Fucs, Patrícia Maria de Moraes Barros

    2013-01-01

    Objective To compare the chronological age and bone age among cerebral palsy patients in the outpatient clinic and its correlation with the type of neurological involvement, gender and functional status. Methods 401 patients with spastic cerebral palsy, and ages ranging from three months to 20 years old, submitted to radiological examination for bone age and analyzed by two independent observers according Greulich & Pyle. Results In the topographic distribution, there was a significant delay (p<0.005) in tetraparetic (17.7 months), hemiparetic (10.1 months), and diparetic patients (7.9 months). In the hemiparetic group, the mean bone age in the affected side was 96.88 months and the uncompromised side was 101.13 months (p<0.005). Regarding functional status, the ambulatory group showed a delay of 18.73 months in bone age (p<0.005). Comparing bone age between genders, it was observed a greater delay in males (13.59 months) than in females (9.63 months), but not statistically significant (p = 0.54). Conclusion There is a delay in bone age compared to chronological age influenced by the topography of spasticity, functional level and gender in patients with cerebral palsy. Level of Evidence IV, Case Series. PMID:24453693

  9. Canine cytochrome P450 (CYP) pharmacogenetics

    PubMed Central

    Court, Michael H.

    2013-01-01

    Synopsis The cytochrome P450 (CYP) drug metabolizing enzymes are essential for the efficient elimination of many clinically used drugs. These enzymes typically display high interindividual variability in expression and function resulting from enzyme induction, inhibition, and genetic polymorphism thereby predisposing patients to adverse drug reactions or therapeutic failure. There are also substantial species differences in CYP substrate specificity and expression that complicate direct extrapolation of information from humans to veterinary species. This article reviews the available published data regarding the presence and impact of genetic polymorphisms on CYP-dependent drug metabolism in dogs in the context of known human-dog CYP differences. Canine CYP1A2, which metabolizes phenacetin, caffeine, and theophylline, is the most widely studied polymorphic canine CYP. A single nucleotide polymorphism resulting in a CYP1A2 premature stop codon (c.1117C>T; R383X) with a complete lack of enzyme is highly prevalent in certain dog breeds including Beagle and Irish wolfhound. This polymorphism was shown to substantially affect the pharmacokinetics of several experimental compounds in Beagles during preclinical drug development. However, the impact on the pharmacokinetics of phenacetin (a substrate specific for human CYP1A2) was quite modest probably because other canine CYPs are capable of metabolizing phenacetin. Other canine CYPs with known genetic polymorphisms include CYP2C41 (gene deletion), as well as CYP2D15, CYP2E1, and CYP3A12 (coding SNPs). However the impact of these variants on drug metabolism in vitro or on drug pharmacokinetics is unknown. Future systematic investigations are needed to comprehensively identify CYP genetic polymorphisms that are predictive of drug effects in canine patients. PMID:23890236

  10. Reversible cerebral vasoconstriction syndrome.

    PubMed

    Lee, R; Ramadan, H; Bamford, J

    2013-01-01

    Reversible cerebral vasoconstriction syndrome (RCVS) is an underdiagnosed condition which usually presents as severe headache with or without neurological deficit. We report the case of a 55-year-old woman who presented with headache and multifocal intracerebral haemorrhage. We review the literature regarding the presentation, pathophysiology and management of RCVS and discuss how to differentiate it from cerebral vasculitis.

  11. Cerebral Palsy (CP) Quiz

    MedlinePlus

    ... SSI file Error processing SSI file Pop Quiz: Cerebral Palsy Language: English Español (Spanish) Recommend on Facebook Tweet ... Sandy is the parent of a child with cerebral palsy and the Board President of Gio’s Garden , a ...

  12. Cytochrome b5 from Giardia lamblia.

    PubMed

    Alam, Samiah; Yee, Janet; Couture, Manon; Takayama, Shin-ichi J; Tseng, Wan-Hsin; Mauk, A Grant; Rafferty, Steven

    2012-12-01

    The protozoan intestinal parasite Giardia lamblia lacks mitochondria and the ability to make haem yet encodes several putative haem-binding proteins, including three of the cytochrome b(5) family. We cloned one of these (gCYTb5-I) and expressed it within Escherichia coli as a soluble holoprotein. UV-visible and resonance Raman spectra of gCYTb5-I resemble those of microsomal cytochrome b(5), and homology modelling supports a structure in which a pair of invariant histidine residues act as axial ligands to the haem iron. The reduction potential of gCYTb5-I is -165 mV vs. SHE and is relatively low compared to most values (-110 to +80 mV) for this class of protein. The amino- and carboxy-terminal sequences that flank the central haem-binding core of the Giardia cytochromes are highly charged and differ from those of other family members. A core gCYTb5-I variant lacking these flanking sequences was also able to bind haem. The presence of one actual and two probable functional cytochromes b(5) in Giardia is evidence of uncharacterized cytochrome-mediated metabolic processes within this medically important protist.

  13. Yeast mutants overproducing iso-cytochromes c

    SciTech Connect

    Sherman, F.; Cardillo, T.S.; Errede, B.; Friedman, L.; McKnight, G.; Stiles, J.I.

    1980-01-01

    For over 15 years, the iso-cytochrome c system in the yeast Saccharomyces cerevisiae has been used to investigate a multitude of problems in genetics and molecular biology. More recently, attention has been focused on using mutants for examining translation and transcriptional processes and for probing regulatory regions governing gene expression. In an effort to explore regulatory mechanisms and to investigate mutational alterations that lead to increased levels of gene products, we have isolated and characterized mutants that overproduce cytochrome c. In this paper we have briefly summarized background information of some essential features of the iso-cytochrome c system and we have described the types of mutants that overproduce iso-1-cytochrome c or iso-2-cytochrome c. Genetic procedures and recombinant DNA procedures were used to demonstrate that abnormally high amounts of gene products occur in mutants as result of duplications of gene copies or of extended alteration of regulatory regions. The results summarized in this paper point out the requirements of gross mutational changes or rearrangements of chromosomal segments for augmenting gene products.

  14. A cytochrome c methyltransferase from Crithidia oncopelti.

    PubMed Central

    Valentine, J; Pettigrew, G W

    1982-01-01

    The mitochondrial cytochrome c-557 of Crithidia oncopelti contains two lysine residues and an N-terminal proline residue that are methylated in vivo by the methyl group of methionine. The purified cytochrome can act as a methyl acceptor for a methyltransferase activity in the cell extract that uses S-adenosylmethionine as methyl donor. Crithidia cytochrome c-557 is by far the best substrate for this methyltransferase of those tested, in spite of the fact that methylation sites are already almost fully occupied. The radioactive uptake of [14C]methyl groups from S-adenosylmethionine occurred only at a lysine residue (-8) and the N-terminal proline residue. This methyltransferase appears to differ from that of Neurospora and yeast [Durban, Nochumson, Kim, Paik & Chan (1978) J. Biol. Chem. 253, 1427-1435; DiMaria, Polastro, DeLange, Kim & Paik (1979) J. Biol. Chem. 254, 4645-4652] in that lysine-72 of horse cytochrome c is a poor acceptor. Also, the Crithidia methyltransferase appears to be stable to carry lysine methylation much further to completion than do the enzymes from yeast and Neurospora, which produce very low degrees of methylation in native cytochromes c. PMID:6282265

  15. Label-free photoacoustic microscopy of cytochromes.

    PubMed

    Zhang, Chi; Zhang, Yu Shrike; Yao, Da-Kang; Xia, Younan; Wang, Lihong V

    2013-02-01

    Photoacoustic microscopy (PAM) has achieved submicron lateral resolution in showing subcellular structures; however, relatively few endogenous subcellular contrasts have so far been imaged. Given that the hemeprotein, mostly cytochromes in general cells, is optically absorbing around the Soret peak (~420 nm), we implemented label-free PAM of cytochromes in cytoplasm for the first time. By measuring the photoacoustic spectra of the oxidized and reduced states of fibroblast lysate and fitting the difference spectrum with three types of cytochromes, we found that the three cytochromes account for more than half the optical absorption in the cell lysate at 420 nm wavelength. Fixed fibroblasts on slides were imaged by PAM at 422 and 250 nm wavelengths to reveal cytoplasms and nuclei, respectively, as confirmed by standard staining histology. PAM was also applied to label-free histology of mouse ear sections by showing cytoplasms and nuclei of various cells. PAM of cytochromes in cytoplasm is expected to be a high-throughput, label-free technique for studying live cell functions, which cannot be accomplished by conventional histology.

  16. Label-free photoacoustic microscopy of cytochromes

    NASA Astrophysics Data System (ADS)

    Zhang, Chi; Zhang, Yu Shrike; Yao, Da-Kang; Xia, Younan; Wang, Lihong V.

    2013-02-01

    Photoacoustic microscopy (PAM) has achieved submicron lateral resolution in showing subcellular structures; however, relatively few endogenous subcellular contrasts have so far been imaged. Given that the hemeprotein, mostly cytochromes in general cells, is optically absorbing around the Soret peak (˜420 nm), we implemented label-free PAM of cytochromes in cytoplasm for the first time. By measuring the photoacoustic spectra of the oxidized and reduced states of fibroblast lysate and fitting the difference spectrum with three types of cytochromes, we found that the three cytochromes account for more than half the optical absorption in the cell lysate at 420 nm wavelength. Fixed fibroblasts on slides were imaged by PAM at 422 and 250 nm wavelengths to reveal cytoplasms and nuclei, respectively, as confirmed by standard staining histology. PAM was also applied to label-free histology of mouse ear sections by showing cytoplasms and nuclei of various cells. PAM of cytochromes in cytoplasm is expected to be a high-throughput, label-free technique for studying live cell functions, which cannot be accomplished by conventional histology.

  17. Label-free photoacoustic microscopy of cytochromes

    PubMed Central

    Zhang, Chi; Zhang, Yu Shrike; Yao, Da-Kang; Xia, Younan

    2013-01-01

    Abstract. Photoacoustic microscopy (PAM) has achieved submicron lateral resolution in showing subcellular structures; however, relatively few endogenous subcellular contrasts have so far been imaged. Given that the hemeprotein, mostly cytochromes in general cells, is optically absorbing around the Soret peak (∼420  nm), we implemented label-free PAM of cytochromes in cytoplasm for the first time. By measuring the photoacoustic spectra of the oxidized and reduced states of fibroblast lysate and fitting the difference spectrum with three types of cytochromes, we found that the three cytochromes account for more than half the optical absorption in the cell lysate at 420 nm wavelength. Fixed fibroblasts on slides were imaged by PAM at 422 and 250 nm wavelengths to reveal cytoplasms and nuclei, respectively, as confirmed by standard staining histology. PAM was also applied to label-free histology of mouse ear sections by showing cytoplasms and nuclei of various cells. PAM of cytochromes in cytoplasm is expected to be a high-throughput, label-free technique for studying live cell functions, which cannot be accomplished by conventional histology. PMID:23370407

  18. Use of Ruthenium Photooxidation Techniques to Study Electron Transfer in the Cytochrome bc1 Complex

    PubMed Central

    Millett, Francis; Durham, Bill

    2009-01-01

    Ruthenium photooxidation methods are presented to study electron transfer between the cytochrome bc1 complex and cytochrome c, and within the cytochrome bc1 complex. Methods are described to prepare a ruthenium cytochrome c derivative, Ruz-39-Cc, by labeling the single sulfhydryl on yeast H39C;C102T iso-1-Cc with the reagent Ru(bpz)2(4-bromomethyl-4′-methylbipyridine). The ruthenium complex attached to Cys-39 on the opposite side of Cc from the heme crevice does not affect the interaction with cyt bc1. Laser excitation of reduced Ruz-39-Cc results in photooxidation of heme c within 1 μs with a yield of 20%. Flash photolysis of a 1:1 complex between reduced yeast cytochrome bc1 and Ruz-39-Cc leads to electron transfer from heme c1 to heme c with a rate constant of 1.4 × 104 s-1. Methods are described for the use of the ruthenium dimer, Ru2D, to photooxidize cyt c1 in the cytochrome bc1 complex within 1 μs with a yield of 20%. Electron transfer from the Rieske iron-sulfur center [2Fe2S] to cyt c1 was detected with a rate constant of 6 × 104 s-1 in R. sphaeroides cyt bc1 using this method. This electron transfer step is rate-limited by the rotation of the Rieske iron-sulfur protein in a conformational gating mechanism. This method provides critical information on the dynamics of rotation of the iron-sulfur protein (ISP) as it transfers electrons from QH2 in the Qo site to cyt c1 These ruthenium photooxidation methods can be used to measure many of the electron transfer reactions in cytochrome bc1 complexes from any source. PMID:19348884

  19. Proteomic profiling of the rat cerebral cortex in sleep and waking

    PubMed Central

    Cirelli, Chiara; Pfister-Genskow, Martha; McCarthy, Diane; Woodbury, Ronald; Tononi, Giulio

    2009-01-01

    Transcriptomic studies have shown that hundreds of genes change their expression levels across the sleep/waking cycle, and found that waking-related and sleep-related mRNAs belong to different functional categories. Proteins, however, rather than DNA or RNA, carry out most of the cellular functions, and direct measurements of protein levels and activity are required to assess the effects of behavioral states on the overall functional state of the cell. Here we used surface-enhanced laser desorption-ionization (SELDI), followed by time-of-flight mass spectrometry, to obtain a large-scale profiling of the proteins in the rat cerebral cortex whose expression is affected by sleep, spontaneous waking, short (6 hours) and long (7 days) sleep deprivation. Each of the 94 cortical samples was profiled in duplicate on 4 different ProteinChip Array surfaces using 2 different matrix molecules. Overall, 1055 protein peaks were consistently detected in cortical samples and 15 candidate biomarkers were selected for identification based on significant changes in multiple conditions (conjunction analysis): 8 “sleep” peaks, 4 “waking” peaks, and 4 “long sleep deprivation” peaks. Four candidate biomarkers were purified and positively identified. The 3353 Da candidate sleep marker was identified as the 30 amino acid C-terminal fragment of rat histone H4. This regions encompasses the osteogenic growth peptide, but a possible link between sleep and this peptide remains highly speculative. Two peaks associated with short and long sleep deprivation were identified as hemoglobin alpha1/2 and beta, respectively, while another peak associated with long sleep deprivation was identified as cytochrome C. The upregulation of hemoglobins and cytochrome C may be part of a cellular stress response triggered by even short periods of sleep loss. PMID:20014652

  20. Kinetics of the interaction of the cytochrome c oxidase of Paracoccus denitrificans with its own and bovine cytochrome c.

    PubMed

    Bolgiano, B; Smith, L; Davies, H C

    1988-04-22

    We have devised a relatively simple method for the purification of cytochrome aa3 of Paracoccus denitrificans with three major subunits similar to those of the larger subunits of the mitochondrial cytochrome oxidase. This preparation has no c-type cytochrome. Studies were made of the oxidation of soluble cytochromes c from bovine heart and Paracoccus. The cytochrome-c oxidase activity was stimulated by low concentrations of either cytochrome c, providing an explanation for the multiphasic nature of plots of v/S versus v. Kinetics of the oxidation of bovine cytochrome c by the Paracoccus oxidase resembled those of bovine oxidase with bovine cytochrome c in every way; the Paracoccus oxidase with bovine cytochrome c can serve as an appropriate model for the mitochondrial system. The kinetics of the oxidation of the soluble Paracoccus cytochrome c by the Paracoccus oxidase were different from those seen with bovine cytochrome c, but resembled the latter if poly(L-lysine) was added to the assays. The important difference between the two species of cytochrome c is the more highly negative hemisphere on the side of the molecule way from the heme crevice in the Paracoccus cytochrome. Thus, the data emphasize the importance of all of the charged groups on cytochrome c in influencing the binding or electron transfer reactions of this oxidation-reduction system. The data also permit some interesting connotations about the possible evolution from the bacterial to the mitochondrial electron transport system.

  1. Cerebral Arterial Thrombosis in Ulcerative Colitis

    PubMed Central

    Casella, Giovanni; Cortelezzi, Claudio Camillo; Marialuisa, DeLodovici; Cariddi Lucia, Princiotta; Elena Pinuccia, Verrengia; Baldini, Vittorio; Segato, Sergio

    2013-01-01

    Thrombosis, mainly venous, is a rare and well-recognized extraintestinal manifestation of inflammatory bowel disease (IBD). We describe a 25-year-old Caucasian man affected by ulcerative colitis and sclerosing cholangitis with an episode of right middle cerebral arterial thrombosis resolved by intraarterial thrombolysis. We perform a brief review of the International Literature. PMID:23864966

  2. Cerebral arterial thrombosis in ulcerative colitis.

    PubMed

    Casella, Giovanni; Cortelezzi, Claudio Camillo; Marialuisa, Delodovici; Cariddi Lucia, Princiotta; Elena Pinuccia, Verrengia; Baldini, Vittorio; Segato, Sergio

    2013-01-01

    Thrombosis, mainly venous, is a rare and well-recognized extraintestinal manifestation of inflammatory bowel disease (IBD). We describe a 25-year-old Caucasian man affected by ulcerative colitis and sclerosing cholangitis with an episode of right middle cerebral arterial thrombosis resolved by intraarterial thrombolysis. We perform a brief review of the International Literature.

  3. Modification of the spectral properties of cytochrome b in mutants of Saccharomyces cerevisiae resistant to 3-(3,4-dichlorophenyl)-1,1-dimethylurea. Mapping at two distinct genetic loci of the split mitochondrial gene of cytochrome b.

    PubMed

    Briquet, M; Goffeau, A

    1981-07-01

    The effects of five inhibitors of the cytochrome bc1 complex: 3-(3,4-dichlorophenyl)-1,1-dimethylurea (diuron), 2-n-heptyl-4-hydroxyquinoline-N-oxide (HpHOQnO), antimycin A, funiculosin and mucidin were measured in submitochondrial particles of strains of the yeast Saccharomyces cerevisiae belonging to two classes of diuron-resistant mutants Diu 1 and Diu 2 which are modified in different exons of the split mitochondrial gene of cytochrome b. 1. The oxidation of NADH and of cytochrome b-561 exhibits a similar resistance to diuron and HpHOQnO in Diu 1 and Diu 2 mutants. 2. No extra reduction of cytochrome b-561 and cytochrome b-565 is observed in the presence of diuron and HpHOQnO. 3. Both Diu 1 and Diu 2 mutants exhibit the red shift of cytochrome b-561 induced by concentrations of HpHOQno 2 -- 3-times higher than those required in the parental strains. 4. The spectral and respiratory effects of antimycin A, funiculosin and mucidin and generally similar in the diuron-resistant mutants and in their parental strains. However a cross-resistance between diuron and antimycin A is indicated in one Diu 2 mutant. 5. From the combined genetic and biochemical data it is concluded that the interaction of diuron and HpHOQnO with cytochrome b is mediated by at least two specific amino acids located apart in the central region of the apocytochrome b peptide coded by mitochondrial DNA. These two amino acids control tightly the extra reduction of cytochromes b-565 and b-561 as well as the flow of electrons through the bc1 complex. However the binding of HpHOQnO required for the expression of the red shift of cytochrome b-561 is only slightly affected by the diu-1 and diu-2 mutations.

  4. A Novel Redox State Heme a Marker in Cytochrome c Oxidase Revealed by Raman Spectroscopy

    NASA Astrophysics Data System (ADS)

    Piccoli, C.; Perna, G.; Scrima, R.; Cela, O.; Rinaldi, R.; Boffoli, D.; Capozzi, V.; Capitanio, N.

    2005-01-01

    This study was aimed to characterize by Raman spectroscopy (excitation line 633 nm) different redox states of the mitochondrial cytochrome c oxidase. The results obtained from a systematic analysis carried out on the mitochondrial enzyme prepared under redox conditions, differently affecting the valence state of the metal prosthetic groups, and a comparison with homologous bacterial heme-copper oxidases, cytochrome c and pyridine hemo-chrome extract revealed a novel redox state marker specifically linked to the redox transition of heme a, peaking at 1645 cm-1, and tentatively assigned to the C=C and/or C=N streching mode of the imidazole ring of a proxymal histidine ligand. The possible involvment of this redox-linked conformational change in the catalytic activity of cytochrome oxidase is discussed.

  5. Role of cytochrome P sub 450 in the control of the production of erythropoietin

    SciTech Connect

    Fandrey, J.; Seydel, F.P.; Siegers, C.P.; Jelkmann, W. )

    1990-01-01

    Effects of agents affecting cytochrome P{sub 450} were studied on the production of erythropoietin (Epo) in cultures of the human hepatoma cell line HepG2. Epo was measured by radioimmunoassay of the culture media after 24 h of incubation. The addition of phenobarbital or 3-methylcholanthrene, which induce cytochrome P{sub 450}, significantly enhanced the formation of Epo. Likewise, the thyroid hormones T{sub 3} and T{sub 4} stimulated the rate of the production of Epo. On the other hand, the formation of Epo was lowered following the addition of diethyl-dithiocarbamate or cysteamine chloride, which inhibit cytochrome P{sub 450}. These findings support the idea that O{sub 2} sensitive hemoproteins of the microsomal mixed-functional oxidases play a role in the control of the synthesis of Epo.

  6. Analysis of mammalian cytochrome P450 structure and function by site-directed mutagenesis.

    PubMed

    Domanski, T L; Halpert, J R

    2001-06-01

    Over the past decade, site-directed mutagenesis has become an essential tool in the study of mammalian cytochrome P450 structure-function relationships. Residues affecting substrate specificity, cooperativity, membrane localization, and interactions with redox partners have been identified using a combination of amino-acid sequence alignments, homology modeling, chimeragenesis, and site-directed mutagenesis. As homology modeling and substrate docking technology continue to improve, the ability to predict more precise functions for specific residues will also advance, making it possible to utilize site-directed mutagenesis to test these predictions. Future studies will employ site-directed mutagenesis to learn more about cytochrome P450 substrate access channels, to define the role of residues that do not lie within substrate recognition sites, to engineer additional soluble forms of microsomal cytochromes P450 for x-ray crystallography, and to engineer more efficient enzymes for drug activation and/or bioremediation.

  7. Role of protein-protein interactions in cytochrome P450-mediated drug metabolism and toxicity.

    PubMed

    Kandel, Sylvie E; Lampe, Jed N

    2014-09-15

    Through their unique oxidative chemistry, cytochrome P450 monooxygenases (CYPs) catalyze the elimination of most drugs and toxins from the human body. Protein-protein interactions play a critical role in this process. Historically, the study of CYP-protein interactions has focused on their electron transfer partners and allosteric mediators, cytochrome P450 reductase and cytochrome b5. However, CYPs can bind other proteins that also affect CYP function. Some examples include the progesterone receptor membrane component 1, damage resistance protein 1, human and bovine serum albumin, and intestinal fatty acid binding protein, in addition to other CYP isoforms. Furthermore, disruption of these interactions can lead to altered paths of metabolism and the production of toxic metabolites. In this review, we summarize the available evidence for CYP protein-protein interactions from the literature and offer a discussion of the potential impact of future studies aimed at characterizing noncanonical protein-protein interactions with CYP enzymes.

  8. RNA fragments mimicking tRNA analogs interact with cytochrome c.

    PubMed

    Pawlowska, Roza; Janicka, Magdalena; Jedrzejczyk, Dominika; Chworos, Arkadiusz

    2016-04-01

    In times, when drug seeking assays focus on the natural molecular triggers and their analogs, a deeper insight into molecular mechanisms governing the initial step of intrinsic apoptosis (cytochrome c release) is essential to suppress the immortality of pathologically changed cells. In this study, we examined RNA molecules mimicking mitochondrial tRNAs interacting with cytochrome c and possibly affecting its cellular function. tRNA analogs were designed and synthesized prior to the conformational analysis and gel assays clearly stating the nucleic acid-protein complex formation. The circular dichroism spectroscopic (CD) and microscale thermophoresis examination revealed the structural and conformational differences between four tRNA analogs in their interactions with cytochrome c. Obtained CD spectra and gel studies resulted in the complex ratio estimation and conclusion that not only the complex formation may be preferential towards specific tRNAs present in the cell, but nucleobase modifications are not essential for such interaction.

  9. Role of Protein–Protein Interactions in Cytochrome P450-Mediated Drug Metabolism and Toxicity

    PubMed Central

    2015-01-01

    Through their unique oxidative chemistry, cytochrome P450 monooxygenases (CYPs) catalyze the elimination of most drugs and toxins from the human body. Protein–protein interactions play a critical role in this process. Historically, the study of CYP–protein interactions has focused on their electron transfer partners and allosteric mediators, cytochrome P450 reductase and cytochrome b5. However, CYPs can bind other proteins that also affect CYP function. Some examples include the progesterone receptor membrane component 1, damage resistance protein 1, human and bovine serum albumin, and intestinal fatty acid binding protein, in addition to other CYP isoforms. Furthermore, disruption of these interactions can lead to altered paths of metabolism and the production of toxic metabolites. In this review, we summarize the available evidence for CYP protein–protein interactions from the literature and offer a discussion of the potential impact of future studies aimed at characterizing noncanonical protein–protein interactions with CYP enzymes. PMID:25133307

  10. Two-dimensional crystallization of monomeric bovine cytochrome c oxidase with bound cytochrome c in reconstituted lipid membranes.

    PubMed

    Osuda, Yukiho; Shinzawa-Itoh, Kyoko; Tani, Kazutoshi; Maeda, Shintaro; Yoshikawa, Shinya; Tsukihara, Tomitake; Gerle, Christoph

    2016-06-01

    Mitochondrial cytochrome c oxidase utilizes electrons provided by cytochrome c for the active vectorial transport of protons across the inner mitochondrial membrane through the reduction of molecular oxygen to water. Direct structural evidence on the transient cytochrome c oxidase-cytochrome c complex thus far, however, remains elusive and its physiological relevant oligomeric form is unclear. Here, we report on the 2D crystallization of monomeric bovine cytochrome c oxidase with tightly bound cytochrome c at a molar ratio of 1:1 in reconstituted lipid membranes at the basic pH of 8.5 and low ionic strength.

  11. Mouse lymphomyeloid cells can function with significantly decreased expression levels of cytochrome C.

    PubMed

    Shilov, E S; Kislyakov, I V; Gorshkova, E A; Zvartsev, R V; Drutskaya, M S; Mufazalov, I A; Skulachev, V P; Nedospasov, S A

    2014-12-01

    Cytochrome c is an indispensable electron carrier in the mitochondrial respiratory chain and also an important mediator of the internal pathway triggering apoptosis. Mice with a complete deficiency of the Cycs gene encoding the somatic cytochrome c die during the embryogenesis. Using the technology of LoxP-cre-dependent tissue-specific recombination, we obtained some mouse strains with significantly reduced expression of cytochrome c in certain cell types ("conditional genetic knockdown"). This knockdown was achieved by abrogation of the normal splicing of the Cycs locus pre-mRNA due to an additional acceptor site inside the stop-cassette neo(r). Previously, we observed embryonic lethality in homozygous mice with the same knockdown of cytochrome c in all cells of the organism. In the present work we studied two novel mouse strains with conditional knockdown of the Cycs gene in T lymphocytes and macrophages. Somewhat surprisingly, the mice of these two strains under normal conditions were not phenotypically different from the wild-type mice, either on the whole organism level or on the level of activity of individual target cells. Thus, the amount of cytochrome c in lymphomyeloid cells does not affect their development and normal functioning.

  12. Control of Insulin Secretion by Cytochrome c and Calcium Signaling in Islets with Impaired Metabolism*

    PubMed Central

    Rountree, Austin M.; Neal, Adam S.; Lisowski, Mark; Rizzo, Norma; Radtke, Jared; White, Sarah; Luciani, Dan S.; Kim, Francis; Hampe, Christiane S.; Sweet, Ian R.

    2014-01-01

    The aim of the study was to assess the relative control of insulin secretion rate (ISR) by calcium influx and signaling from cytochrome c in islets where, as in diabetes, the metabolic pathways are impaired. This was achieved either by culturing isolated islets at low (3 mm) glucose or by fasting rats prior to the isolation of the islets. Culture in low glucose greatly reduced the glucose response of cytochrome c reduction and translocation and ISR, but did not affect the response to the mitochondrial fuel α-ketoisocaproate. Unexpectedly, glucose-stimulated calcium influx was only slightly reduced in low glucose-cultured islets and was not responsible for the impairment in glucose-stimulated ISR. A glucokinase activator acutely restored cytochrome c reduction and translocation and ISR, independent of effects on calcium influx. Islets from fasted rats had reduced ISR and cytochrome c reduction in response to both glucose and α-ketoisocaproate despite normal responses of calcium. Our data are consistent with the scenario where cytochrome c reduction and translocation are essential signals in the stimulation of ISR, the loss of which can result in impaired ISR even when calcium response is normal. PMID:24841202

  13. Detection of human lung cytochromes P450 that are immunochemically related to cytochrome P450IIE1 and cytochrome P450IIIA.

    PubMed

    Wheeler, C W; Wrighton, S A; Guenthner, T M

    1992-07-07

    We have used monoclonal antibodies that were prepared against and specifically recognize human hepatic cytochromes P450 as probes for solid phase radioimmunoassay and Western immunoblotting to directly demonstrate the presence in human lung microsomes of cytochromes P450 immunochemically related to human liver cytochromes P450IIE1 (CYP2E1) and P450IIIA (CYP3A). The detected levels of these cytochromes are much lower than levels in human liver microsomes, but similar to the levels seen in microsomes from untreated baboon lung. Proteins immunochemically related to two other constitutive hepatic cytochromes P450, cytochrome P450IIC8 (CYP2C8) and cytochrome P450IIC9 (CYP2C9), were not detectable in lung microsomes.

  14. Reactive intermediates in cytochrome p450 catalysis.

    PubMed

    Krest, Courtney M; Onderko, Elizabeth L; Yosca, Timothy H; Calixto, Julio C; Karp, Richard F; Livada, Jovan; Rittle, Jonathan; Green, Michael T

    2013-06-14

    Recently, we reported the spectroscopic and kinetic characterizations of cytochrome P450 compound I in CYP119A1, effectively closing the catalytic cycle of cytochrome P450-mediated hydroxylations. In this minireview, we focus on the developments that made this breakthrough possible. We examine the importance of enzyme purification in the quest for reactive intermediates and report the preparation of compound I in a second P450 (P450ST). In an effort to bring clarity to the field, we also examine the validity of controversial reports claiming the production of P450 compound I through the use of peroxynitrite and laser flash photolysis.

  15. Nerval influences on liver cytochrome P450.

    PubMed

    Klinger, W; Karge, E; Danz, M; Krug, M

    1995-09-01

    In male young adult Wistar rats the influences of nucleus raphe electrocoagulation, spinal cord dissection (cordotomy between C7 and Th1), vagotomy and denervation of liver hilus by phenol on liver cytochrome P450-system (cytochrome P450 concentration, ethylmorphine N-demethylation and ethoxycoumarin O-deethylation activities, hexobarbitone sleeping time) were investigated. In general the influences were small or negligible when compared with sham operated controls, only after vagotomy the depressing effect of sham operation was abolished. In all cases sham operation had a depressing effect until up to five weeks after operation.

  16. Reactive Intermediates in Cytochrome P450 Catalysis*

    PubMed Central

    Krest, Courtney M.; Onderko, Elizabeth L.; Yosca, Timothy H.; Calixto, Julio C.; Karp, Richard F.; Livada, Jovan; Rittle, Jonathan; Green, Michael T.

    2013-01-01

    Recently, we reported the spectroscopic and kinetic characterizations of cytochrome P450 compound I in CYP119A1, effectively closing the catalytic cycle of cytochrome P450-mediated hydroxylations. In this minireview, we focus on the developments that made this breakthrough possible. We examine the importance of enzyme purification in the quest for reactive intermediates and report the preparation of compound I in a second P450 (P450ST). In an effort to bring clarity to the field, we also examine the validity of controversial reports claiming the production of P450 compound I through the use of peroxynitrite and laser flash photolysis. PMID:23632017

  17. [A subacute dementia: Inflammatory cerebral amyloid angiopathy].

    PubMed

    Charef, S; Leblanc, A; Guibourg, B; Quintin-Roue, I; Ben Salem, D; Zagnoli, F

    2015-12-01

    We report a case of inflammatory cerebral amyloid angiopathy (CAA) that led to rapid cognitive decline, seizures, visual hallucinations, hyperproteinorrachia and right hemispheric leukopathy. Brain biopsy gave the diagnosis of CAA. Although no inflammatory infiltrate was found in the biopsy sample, corticosteroids led to a regression of the radiological lesions without significant clinical improvement. CAA is a rare disease, defined by lesions of classical cerebral amyloid angiopathy and perivascular infiltrates in contact with the affected vessels. In cases of rapidly progressive dementia associated with leukopathy, inflammatory amyloid angiopathy should be considered as cognitive disorders may improve after immunosuppressive therapy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  18. Genetic characterization of Bagarius species using cytochrome c oxidase I and cytochrome b genes.

    PubMed

    Nagarajan, Muniyandi; Raja, Manikam; Vikram, Potnuru

    2016-09-01

    In this study, we first inferred the genetic variability of two Bagarius bagarius populations collected from Ganges and Brahmaputra rivers of India using two mtDNA markers. Sequence analysis of COI gene did not show significant differences between two populations whereas cytochrome b gene showed significant differences between two populations. Followed by, genetic relationship of B. bagarius and B. yarrielli was analyzed using COI and cytochrome b gene and the results showed a higher level genetic variation between two species. The present study provides support for the suitability of COI and cytochrome b genes for the identification of B. bagarius and B. yarrielli.

  19. Effects of Muscle-Specific Oxidative Stress on Cytochrome c Release and Oxidation-Reduction Potential Properties.

    PubMed

    Ke, Yiling; Mitacek, Rachel M; Abraham, Anupam; Mafi, Gretchen G; VanOverbeke, Deborah L; DeSilva, Udaya; Ramanathan, Ranjith

    2017-09-06

    Mitochondria play a significant role in beef color. However, the role of oxidative stress in cytochrome c release and mitochondrial degradation is not clear. The objective was to determine the effects of display time on cytochrome c content and oxidation-reduction potential (ORP) of beef longissimus lumborum (LL) and psoas major (PM) muscles. PM discolored by day 3 compared with LL. On day 0, mitochondrial content and mitochondrial oxygen consumption were greater in PM than LL. However, mitochondrial content and oxygen consumption were lower (P < 0.05) in PM than LL by day 7. Conversely, cytochrome c content in sarcoplasm was greater on days 3 and 7 for PM than LL. There were no significant differences in ORP for LL during display, but ORP increased for PM on day 3 when compared with day 0. The results suggest that muscle-specific oxidative stress can affect cytochrome c release and ORP changes.

  20. Potentiometric analysis of the cytochromes of an Escherichia coli mutant strain lacking the cytochrome d terminal oxidase complex.

    PubMed Central

    Lorence, R M; Green, G N; Gennis, R B

    1984-01-01

    A combination of potentiometric analysis and electrochemically poised low-temperature difference spectroscopy was used to examine a mutant strain of Escherichia coli that was previously shown by immunological criteria to be lacking the cytochrome d terminal oxidase. It was shown that this strain is missing cytochromes d, a1, and b558 and that the cytochrome composition of the mutant is similar to that of the wild-type strain grown under conditions of high aeration. The data indicate that the high-aeration branch of the respiratory chain contains two cytochrome components, b556 (midpoint potential [Em] = +35 mV) and cytochrome o (Em = +165 mV). The latter component binds to CO and apparently has a reduced-minus-oxidized split-alpha band with peaks at 555 and 562 nm. When the wild-type strain was grown under conditions of low aeration, the components of the cytochrome d terminal oxidase complex were observed: cytochrome d (Em = +260 mV), cytochrome a1 (Em = +150 mV) and cytochrome b558 (Em = +180 mV). All cytochromes appeared to undergo simple one-electron oxidation-reduction reactions. In the absence of CO, cytochromes b558 and o have nearly the same Em values. In the presence of CO, the Em of cytochrome o is raised, thus allowing cytochromes b558 and o to be individually quantitated by potentiometric analysis when they are both present. PMID:6317644

  1. [Cardioprotective effect of drugs with antioxidant activity in acute cerebral ischemia].

    PubMed

    Stoliarova, V V

    2001-01-01

    The bioelectric cardiac activity was studied in the experiments on white mice with an acute cerebral blood circulation disorder. It was found that he resulting EEG changes possess a specific character, with the sympathoadrenal system stimulation playing an important role in the acute cerebrocardiac syndrome development. The antioxidant-type agents such as emoxypine (50 mg/kg), mexidol (50 mg/kg), and cytochrome C (10 mg/kg) produce a significant cardioprotective effect in the test animals with experimental cerebral ischemia, which was comparable with the effect of propranolol (obsidane) (0.1 mg/kg).

  2. Evolution of cytochrome c genes and pseudogenes.

    PubMed

    Wu, C I; Li, W H; Shen, J J; Scarpulla, R C; Limbach, K J; Wu, R

    1986-01-01

    A statistical analysis of the nucleotide sequences of cytochrome c genes from four species of animals and two of yeast and of cytochrome c pseudogenes from rat, mouse, and human was conducted. It was estimated that animals and yeast diverged 1.2 billion years ago, that the two duplicated genes DC3 and DC4 in Drosophila diverged 520 million years ago, and that the two duplicated genes Iso-1 and Iso-2 in the yeast Saccharomyces cerevisiae diverged 200 million years ago. DC3 is expressed at a low level and has evolved 3 times faster than DC4. This observation supports the neutralist view that relaxation of functional constraints is a more likely cause of accelerated evolution following gene duplication than is advantageous mutation. All the rodent pseudogenes examined appear to be processed pseudogenes derived directly from the functional genes, and most of them apparently arose after the mouse-rat split. No event of gene conversion could be detected between any pair of the rodent pseudogenes. Our analysis suggests that the human cytochrome c gene has evolved at a rate comparable to the average rate for pseudogenes, whereas some human cytochrome c pseudogenes have evolved at an exceptionally low rate.

  3. Cytochrome C: A Biochemistry Laboratory Course

    ERIC Educational Resources Information Center

    Vincent, John B.; Woski, Stephen A.

    2005-01-01

    A laboratory course called cytochrome c that focuses on the theme of biochemical research is presented. The students follow this course by incorporating team-investigation and self-directed experimentation that provides them an opportunity to experience the excitement of research.

  4. Design and Use of Photoactive Ruthenium Complexes to Study Electron Transfer within Cytochrome bc1 and from Cytochrome bc1 to Cytochrome c

    PubMed Central

    Millett, Francis; Havens, Jeffrey; Rajagukguk, Sany; Durham, Bill

    2012-01-01

    The cytochrome bc1 complex (ubiquinone:cytochrome c oxidoreductase) is the central integral membrane protein in the mitochondrial respiratory chain as well as the electron-transfer chains of many respiratory and photosynthetic prokaryotes. Based on X-ray crystallographic studies of cytochrome bc1, a mechanism has been proposed in which the extrinsic domain of the iron-sulfur protein first binds to cytochrome b where it accepts an electron from ubiquinol in the Qo site, and then rotates by 57o to a position close to cytochrome c1 where it transfers an electron to cytochrome c1. This review describes the development of a ruthenium photooxidation technique to measure key electron transfer steps in cytochrome bc1, including rapid electron transfer from the iron-sulfur protein to cytochrome c1. It was discovered that this reaction is rate-limited by the rotational dynamics of the iron-sulfur protein rather than true electron transfer. A conformational linkage between the occupant of the Qo ubiquinol binding site and the rotational dynamics of the iron-sulfur protein was discovered which could play a role in the bifurcated oxidation of ubiquinol. A ruthenium photoexcitation method is also described for the measurement of electron transfer from cytochrome c1 to cytochrome c. This article is part of a special issue entitled: Respiratory Complex III. PMID:22985600

  5. Cerebral Cavernous Malformations (CCM)

    MedlinePlus

    ... Contact Registry Interest Form Contact Us | Login Disorder Definitions Learn More > Disorder Definitions Cerebral Cavernous Malformations (CCM) ... until it is too late to salvage vision. Routine screening is very important, even if there are ...

  6. Cerebral Aneurysms Fact Sheet

    MedlinePlus

    ... Caregiver Education » Fact Sheets Cerebral Aneurysms Fact Sheet Table of Contents (click to jump to sections) What ... Information Page NINDS Epilepsy Information Page NINDS Familial Periodic Paralyses Information Page NINDS Farber's Disease Information Page ...

  7. Acquired Cerebral Trauma: Epilogue.

    ERIC Educational Resources Information Center

    Bigler, Erin D., Ed.

    1988-01-01

    The article summarizes a series of articles concerning acquired cerebral trauma. Reviewed are technological advances, treatment, assessment, potential innovative therapies, long-term outcome, family impact of chronic brain injury, and prevention. (DB)

  8. Cerebral amyloid angiopathy

    MedlinePlus

    ... 911) if you have sudden loss of movement , sensation, vision, or speech. Alternative Names Amyloidosis - cerebral; CAA; Congophilic angiopathy Images Amyloidosis on the fingers Arteries of the brain References Kase CS, Shoamanesh A. Intracerebral hemorrhage. In: Daroff ...

  9. Cerebral hemodynamic changes in stroke during sleep-disordered breathing.

    PubMed

    Pizza, Fabio; Biallas, Martin; Kallweit, Ulf; Wolf, Martin; Bassetti, Claudio L

    2012-07-01

    Sleep-disordered breathing (SDB) negatively impacts stroke outcome. Near-infrared spectroscopy showed the acute cerebral hemodynamic effects of SDB. Eleven patients (7 men, age 61±13 years) with acute/subacute middle cerebral artery stroke (National Institutes of Health Stroke Scale score 10±7) and SDB (apnea-hypopnea index 32±28/hour) were assessed with nocturnal polysomnography and bilateral near-infrared spectroscopy recording. Cerebral oxygenation and hemoglobin concentration changes during obstructive and central apneas were analyzed. During SDB, near-infrared spectroscopy showed asymmetrical patterns of cerebral oxygenation and hemoglobin concentrations with changes significantly larger on the unaffected compared with the affected hemisphere. Brain tissue hypoxia was more severe during obstructive compared with central apneas. Profound cerebral deoxygenation effects of SDB occurred in acute/subacute stroke. These changes may contribute to poor outcome, arising in the possibility of a potential benefit of SDB treatment in stroke management.

  10. Isolation of ubiquinol oxidase from Paracoccus denitrificans and resolution into cytochrome bc1 and cytochrome c-aa3 complexes.

    PubMed

    Berry, E A; Trumpower, B L

    1985-02-25

    An enzyme complex with ubiquinol-cytochrome c oxidoreductase, cytochrome c oxidase, and ubiquinol oxidase activities was purified from a detergent extract of the plasma membrane of aerobically grown Paracoccus denitrificans. This ubiquinol oxidase consists of seven polypeptides and contains two b cytochromes, cytochrome c1, cytochrome aa3, and a previously unreported c-type cytochrome. This c-type cytochrome has an apparent Mr of 22,000 and an alpha absorption maximum at 552 nm. Retention of this c cytochrome through purification presumably accounts for the independence of ubiquinol oxidase activity on added cytochrome c. Ubiquinol oxidase can be separated into a 3-subunit bc1 complex, a 3-subunit c-aa3 complex, and a 57-kDa polypeptide. This, together with detection of covalently bound heme and published molecular weights of cytochrome c1 and the subunits of cytochrome c oxidase, allows tentative identification of most of the subunits of ubiquinol oxidase with the prosthetic groups present. Ubiquinol oxidase contains cytochromes corresponding to those of the mitochondrial bc1 complex, cytochrome c oxidase complex, and a bound cytochrome c. Ubiquinol-cytochrome c oxidoreductase activity of the complex is inhibited by inhibitors of the mitochondrial bc1 complex. Thus it seems likely that the pathway of electron transfer through the bc1 complex of ubiquinol oxidase is similar to that through the mitochondrial bc1 complex. The number of polypeptides present is less than half the number in the corresponding mitochondrial complexes. This structural simplicity may make ubiquinol oxidase from P. denitrificans a useful system with which to study the mechanisms of electron transfer and energy transduction in the bc1 and cytochrome c oxidase sections of the respiratory chain.

  11. Zonation of hepatic cytochrome P-450 expression and regulation.

    PubMed Central

    Oinonen, T; Lindros, K O

    1998-01-01

    The CYP genes encode enzymes of the cytochrome P-450 superfamily. Cytochrome P-450 (CYP) enzymes are expressed mainly in the liver and are active in mono-oxygenation and hydroxylation of various xenobiotics, including drugs and alcohols, as well as that of endogenous compounds such as steroids, bile acids, prostaglandins, leukotrienes and biogenic amines. In the liver the CYP enzymes are constitutively expressed and commonly also induced by chemicals in a characteristic zonated pattern with high expression prevailing in the downstream perivenous region. In the present review we summarize recent studies, mainly based on rat liver, on the factors regulating this position-dependent expression and induction. Pituitary-dependent signals mediated by growth hormone and thyroid hormone seem to selectively down-regulate the upstream periportal expression of certain CYP forms. It is at present unknown to what extent other hormones that also affect total hepatic CYP activities, i.e. insulin, glucagon, glucocorticoids and gonadal hormones, act zone-specifically. The expression and induction of CYP enzymes in the perivenous region probably have important toxicological implications, since many CYP-activated chemicals cause cell injury primarily in this region of the liver. PMID:9405271

  12. Oxidative modification of cytochrome c by singlet oxygen

    PubMed Central

    Kim, Junhwan; Rodriguez, Myriam E.; Guo, Ming; Kenney, Malcolm E.; Oleinick, Nancy L.; Anderson, Vernon E.

    2008-01-01

    Singlet oxygen (1O2) is a reactive oxygen species that may be generated in biological systems. Photodynamic therapy generates 1O2 by photoexcitation of sensitizers resulting in intracellular oxidative stress and induction of apoptosis. 1O2 oxidizes amino acid side chains of proteins and inactivates enzymes when generated in vitro. Among proteogenic amino acids, His, Tyr, Met, Cys, and Trp are known to be oxidized by 1O2 at physiological pH. However, there is a lack of direct evidence of oxidation of proteins by 1O2. Because 1O2 is difficult to detect in cells, identifying oxidized cellular products uniquely derived from 1O2 could serve as a marker of its presence. In the present study, 1O2 reactions with model peptides analyzed by tandem mass spectrometry provide insight into the mass of prominent adducts formed with the reactive amino acids. Analysis by MALDI-TOF and tandem mass spectrometry of peptides of cytochrome c exposed to 1O2 generated by photoexcitation of the phthalocyanine Pc 4 showed unique oxidation products, which might be used as markers of the presence of 1O2 in the mitochondrial intermembrane space. Differences in the elemental composition of the oxidized amino acid residues observed with cytochrome c and the model peptides suggest the protein environment can affect the oxidation pathway. PMID:18242196

  13. Fatty acids as modulators of cytochrome c oxidase in proteoliposomes.

    PubMed Central

    Sharpe, M; Perin, I; Wrigglesworth, J; Nicholls, P

    1996-01-01

    The control of cytochrome c oxidase turnover in proteoliposomes by membrane potential (delta psi) and by pH gradient (delta pH) is probably kinetic in nature, and inhibition by valinomycin and stimulation by nigericin indicate that delta pH exerts a greater influence than does an equivalent delta psi. Oleic acid at 100 microM removes all delta psi and delta pH control, whereas a similar concentration of palmitic acid increases turnover but does not completely abolish control. Valinomycin acts synergistically with both fatty acids, indicating that the latter can act as H+/K+ exchangers, but neither fatty acid alone markedly affects delta pH, showing that they cannot fully mimic nigericin. Oleate, but not palmitate, diminishes delta psi, and can move electrophoretically as oleate anion. Submicromolar palmitic acid concentrations partly stimulate turnover in delta psi- and delta pH-controlled proteoliposomes, as reported by Labonia, Muller and Azzi [(1988) Biochem. J. 254, 130-145], which might represent a direct effect on cytochrome c oxidase. The ubiquity of fatty acids in biological membranes suggests that these substances might be responsible for limiting respiratory control and enzyme activity in vivo. PMID:8973566

  14. Nanomedicine in cerebral palsy

    PubMed Central

    Balakrishnan, Bindu; Nance, Elizabeth; Johnston, Michael V; Kannan, Rangaramanujam; Kannan, Sujatha

    2013-01-01

    Cerebral palsy is a chronic childhood disorder that can have diverse etiologies. Injury to the developing brain that occurs either in utero or soon after birth can result in the motor, sensory, and cognitive deficits seen in cerebral palsy. Although the etiologies for cerebral palsy are variable, neuroinflammation plays a key role in the pathophysiology of the brain injury irrespective of the etiology. Currently, there is no effective cure for cerebral palsy. Nanomedicine offers a new frontier in the development of therapies for prevention and treatment of brain injury resulting in cerebral palsy. Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury. These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth. In this review, the current advances in nanotechnology for treatment of brain injury are discussed with specific relevance to cerebral palsy. Future directions that would facilitate clinical translation in neonates and children are also addressed. PMID:24204146

  15. Nanomedicine in cerebral palsy.

    PubMed

    Balakrishnan, Bindu; Nance, Elizabeth; Johnston, Michael V; Kannan, Rangaramanujam; Kannan, Sujatha

    2013-01-01

    Cerebral palsy is a chronic childhood disorder that can have diverse etiologies. Injury to the developing brain that occurs either in utero or soon after birth can result in the motor, sensory, and cognitive deficits seen in cerebral palsy. Although the etiologies for cerebral palsy are variable, neuroinflammation plays a key role in the pathophysiology of the brain injury irrespective of the etiology. Currently, there is no effective cure for cerebral palsy. Nanomedicine offers a new frontier in the development of therapies for prevention and treatment of brain injury resulting in cerebral palsy. Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury. These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth. In this review, the current advances in nanotechnology for treatment of brain injury are discussed with specific relevance to cerebral palsy. Future directions that would facilitate clinical translation in neonates and children are also addressed.

  16. Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

    PubMed

    Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

    2014-07-01

    The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects.

  17. Production of 20-HETE and its role in autoregulation of cerebral blood flow.

    PubMed

    Gebremedhin, D; Lange, A R; Lowry, T F; Taheri, M R; Birks, E K; Hudetz, A G; Narayanan, J; Falck, J R; Okamoto, H; Roman, R J; Nithipatikom, K; Campbell, W B; Harder, D R

    2000-07-07

    In the brain, pressure-induced myogenic constriction of cerebral arteriolar muscle contributes to autoregulation of cerebral blood flow (CBF). This study examined the role of 20-HETE in autoregulation of CBF in anesthetized rats. The expression of P-450 4A protein and mRNA was localized in isolated cerebral arteriolar muscle of rat by immunocytochemistry and in situ hybridization. The results of reverse transcriptase-polymerase chain reaction studies revealed that rat cerebral microvessels express cytochrome P-450 4A1, 4A2, 4A3, and 4A8 isoforms, some of which catalyze the formation of 20-HETE from arachidonic acid. Cerebral arterial microsomes incubated with [(14)C]arachidonic acid produced 20-HETE. An elevation in transmural pressure from 20 to 140 mm Hg increased 20-HETE concentration by 6-fold in cerebral arteries as measured by gas chromatography/mass spectrometry. In vivo, inhibition of vascular 20-HETE formation with N-methylsulfonyl-12, 12-dibromododec-11-enamide (DDMS), or its vasoconstrictor actions using 15-HETE or 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE), attenuated autoregulation of CBF to elevations of arterial pressure. In vitro application of DDMS, 15-HETE, or 20-HEDE eliminated pressure-induced constriction of rat middle cerebral arteries, and 20-HEDE and 15-HETE blocked the vasoconstriction action of 20-HETE. Taken together, these data suggest an important role for 20-HETE in the autoregulation of CBF.

  18. Enhancement of DMNQ-induced hepatocyte toxicity by cytochrome P450 inhibition

    SciTech Connect

    Ishihara, Yasuhiro; Shiba, Dai; Shimamoto, Norio . E-mail: n-shimamoto@kph.bunri-u.ac.jp

    2006-07-15

    Two mechanisms have been proposed to explain quinone cytotoxicity: oxidative stress via the redox cycle and the arylation of intracellular nucleophiles. As the redox cycle is catalyzed by NADPH cytochrome P450 reductase, cytochrome P450 systems are expected to be related to the cytotoxicity induced by redox-cycling quinones. Thus, we investigated the relationship between cytochrome P450 systems and quinone toxicity for rat primary hepatocytes using an arylator, 1,4-benzoquinone (BQ), and a redox cycler, 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). The hepatocyte toxicity of both BQ and DMNQ increased in a time- and dose-dependent manner. Pretreatment with cytochrome P450 inhibitors, such as SKF-525A (SKF), ketoconazole and 2-methy-1,2-di-3-pyridyl-1-propanone, enhanced the hepatocyte toxicity induced by DMNQ but did not affect BQ-induced hepatocyte toxicity. The production of superoxide anion and the levels of glutathione disulfide and thiobarbituric-acid-reactive substances were increased by treatment with DMNQ, and SKF pretreatment further enhanced their increases. In addition, NADPH oxidation in microsomes was increased by treatment with DMNQ and further augmented by pretreatment with SKF, and a NADPH cytochrome P450 reductase inhibitor, diphenyleneiodonium chloride completely suppressed NADPH oxidations increased by treatment with either DMNQ- or DMNQ + SKF. Pretreatment with antioxidants, such as {alpha}-tocopherol, reduced glutathione, N-acetyl cysteine or an iron ion chelator deferoxamine, totally suppressed DMNQ- and DMNQ + SKF-induced hepatocyte toxicity. These results indicate that the hepatocyte toxicity of redox-cycling quinones is enhanced under cytochrome P450 inhibition, and that this enhancement is caused by the potentiation of oxidative stress.

  19. Engineering of a functional human NADH-dependent cytochrome P450 system

    PubMed Central

    Döhr, Olaf; Paine, Mark J. I.; Friedberg, Thomas; Roberts, Gordon C. K.; Wolf, C. Roland

    2001-01-01

    A functional human NADH-dependent cytochrome P450 system has been developed by altering the cofactor preference of human NADPH cytochrome P450 reductase (CPR), the redox partner for P450s. This has been achieved by a single amino acid change of the conserved aromatic amino acid Trp-676, which covers the re-side of the FAD isoalloxazine ring in the nicotinamide-binding site. Of the mutations made, the substitution of Trp-676 with alanine (W676A) resulted in a functional NADH-dependent enzyme, which catalyzed the reduction of cytochrome c and ferricyanide as well as facilitated the metabolism of 7-ethoxyresorufin by CYP1A2. Kinetic analysis measuring cytochrome c activity revealed that the NADH-dependent kcat of W676A is equivalent (90%) to the NADPH-dependent kcat of the wild-type enzyme, with W676A having an approximately 1,000-fold higher specificity for NADH. The apparent KMNADPH and KMNADH values of W676A are 80- and 150-fold decreased, respectively. In accordance with structural data, which show a bipartite binding mode of NADPH, substitution of Trp-676 does not affect 2′-AMP binding as seen by the inhibition of both wild-type CPR and the W676A mutant. Furthermore, NADPH was a potent inhibitor of the W676A NADH-dependent cytochrome c reduction and CYP1A2 activity. Overall, the results show that Trp-676 of human CPR plays a major role in cofactor discrimination, and substitution of this conserved aromatic residue with alanine results in an efficient NADH-dependent cytochrome P450 system. PMID:11136248

  20. Sensitivity of near infrared spectroscopy to cerebral and extra-cerebral oxygenation changes is determined by emitter-detector separation.

    PubMed

    Germon, T J; Evans, P D; Manara, A R; Barnett, N J; Wall, P; Nelson, R J

    1998-07-01

    To examine the effect of two emitter-detector separations (2.7 and 5.5 cm) on the detection of changes in cerebral and extra-cerebral tissue oxygenation using near infrared spectroscopy (NIRS). Two NIR detectors were placed on the scalp 2.7 and 5.5 cm from a single NIR emitter. Changes in deoxyhaemoglobin (HHb), oxyhaemoglobin (O2Hb),oxidised cytochrome C oxidase (Cyt) and total haemoglobin (tHb) were recorded from each detector during the induction of cerebral oligaemia (transition from hypercapnia to hypocapnia) and scalp hyperaemia (following release of a scalp tourniquet). Cerebral oligaemia (mean decrease in middle cerebral artery blood flow velocity of 44%) induced by a mean reduction in end tidal CO2 of 18 mmHg was accompanied by a significant increase in the spectroscopic signal for HHb and a decrease in the O2Hb signal. The signal change per unit photon path length detected at 5.5 cm was significantly greater for HHb (p = 0.007) than that detected at 2.7 cm. In contrast, the increase in all chromophores detected at 5.5 cm during scalp hyperaemia was significantly less than that detected at 2.7 cm (p<0.001). The differing sensitivity of the proximal and distal channels to changes in cerebral and extracerebral oxygenation is compatible with theoretical models of NIR light transmission in the adult head and may provide a basis for spatially resolving these changes. The optimal emitter-detector separation for adult NIRS requires further investigation and may differ between individuals.

  1. Isolation and purification of the cytochrome oxidase of Azotobacter vinelandii.

    PubMed

    Jurtshuk, P; Mueller, T J; Wong, T Y

    1981-09-14

    A membrane-bound cytochrome oxidase for Azobacter vinelandii was purified 20-fold using a detergent-solubilization procedure. Activity was monitored using as ascorbate-TMPD oxidation assay. The oxidase was 'solubilized' from a sonic-type electron-transport particle (R3 fraction) using Triton X-100 and deoxycholate. Low detergent concentrations first solubilized the flavoprotein oxidoreductases, then higher concentrations of Triton X-100 and KCl solubilized the oxidase, which was precipitated at 27-70% (NH4)2SO4. The highly purified cytochrome oxidase has a V of 60-78 microgatom O consumed/min per mg protein. TMPD oxidation by the purified enzyme was inhibited by CO, KCN, NaN3 and NH2OH; NaNO2 (but not NaNO3) also had a potent inhibitory effect. Spectral analyses revealed two major hemoproteins, the c-type cytochrome c4 and cytochrome o; cytochromes a1 and d were not detected. The Azotobacter cytochrome oxidase is an integrated cytochrome c4-o complex, TMPD-dependent cytochrome oxidase activity being highest in preparations having a high c-type cytochrome content. This TMPD-dependent cytochrome oxidase serves as a major oxygen-activation site for the A. vinelandii respiratory chain. It appears functionally analogous to cytochrome a+a3 oxidase of mammalian mitochondria.

  2. Isolation and characterization of a complementary DNA specific for human aromatase-system cytochrome P-450 mRNA.

    PubMed Central

    Evans, C T; Ledesma, D B; Schulz, T Z; Simpson, E R; Mendelson, C R

    1986-01-01

    A cloned complementary DNA sequence has been isolated from a human placental cDNA library in the bacteriophage expression vector lambda gt11 after screening with polyclonal antibodies against human placental aromatase-system cytochrome P-450 (P-450Arom). A single recombinant clone, lambda hAROM1, was characterized by its ability to generate a beta-galactosidase fusion protein that reacted independently with polyclonal antibodies raised against beta-galactosidase and cytochrome P-450Arom and with monoclonal antibodies specific for cytochrome P-450Arom. The cDNA insert, which was found to be 1.8 kilobases in length, was radiolabeled and used to analyze poly(A)+ RNA isolated from human placenta and total RNA isolated from human adipose stromal cells cultured in the absence or presence of regulatory factors. The radiolabeled cDNA hybridized to several size species of mRNA in both placental and adipose stromal cell RNA fractions. Changes in the levels of adipose stromal cell RNA that hybridized to the cDNA insert were associated with comparable changes in the levels of translatable cytochrome P-450Arom mRNA and aromatase system activity. These findings are indicative that lambda hAROM1 contains DNA sequences complementary to human cytochrome P-450Arom mRNA and are suggestive that regulatory factors affect aromatase activity by altering the transcriptional activity of the cytochrome P-450Arom gene. Images PMID:3018730

  3. The cytochrome b5 reductase HPO-19 is required for biosynthesis of polyunsaturated fatty acids in Caenorhabditis elegans.

    PubMed

    Zhang, Yuru; Wang, Haizhen; Zhang, Jingjing; Hu, Ying; Zhang, Linqiang; Wu, Xiaoyun; Su, Xiong; Li, Tingting; Zou, Xiaoju; Liang, Bin

    2016-04-01

    Polyunsaturated fatty acids (PUFAs) are fatty acids with backbones containing more than one double bond, which are introduced by a series of desaturases that insert double bonds at specific carbon atoms in the fatty acid chain. It has been established that desaturases need flavoprotein-NADH-dependent cytochrome b5 reductase (simplified as cytochrome b5 reductase) and cytochrome b5 to pass through electrons for activation. However, it has remained unclear how this multi-enzyme system works for distinct desaturases. The model organism Caenorhabditis elegans contains seven desaturases (FAT-1, -2, -3, -4, -5, -6, -7) for the biosynthesis of PUFAS, providing an excellent model in which to characterize different desaturation reactions. Here, we show that RNAi inactivation of predicted cytochrome b5 reductases hpo-19 and T05H4.4 led to increased levels of C18:1n-9 but decreased levels of PUFAs, small lipid droplets, decreased fat accumulation, reduced brood size and impaired development. Dietary supplementation with different fatty acids showed that HPO-19 and T05H4.4 likely affect the activity of FAT-1, FAT-2, FAT-3, and FAT-4 desaturases, suggesting that these four desaturases use the same cytochrome b5 reductase to function. Collectively, these findings indicate that cytochrome b5 reductase HPO-19/T05H4.4 is required for desaturation to biosynthesize PUFAs in C. elegans. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Research of Sleep Disorders in Patients with Acute Cerebral Infarction.

    PubMed

    Chen, Xiaofang; Bi, Hongye; Zhang, Meiyun; Liu, Haiyan; Wang, Xueying; Zu, Ruonan

    2015-11-01

    The purpose of this study is to investigate the incidence of sleep disorders (SD), characteristic of cerebral infarction patients with different parts affected. The research selected 101 patients with a first occurrence of acute cerebral infarction as the experimental group, and 86 patients without cerebral infarction as controls. Polysomnography, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and US National Stroke Scale were assessed. Compared with control group, the incidence of SD was higher in experimental group (P < .05), and the incidence of SD in women was more frequent in experimental group (P < .05). There was no significant difference in the types of SD patients with acute cerebral infarction. In addition, the sleep quality of cerebral infarction patients with different parts affected was different: the sleep quality of left hemisphere infarction patients was poor compared with the right one, and the sleep quality of anterior circulation patients was poor compared with posterior circulation patients. Patients with thalamus infarction had a longer sleep time and a shorter sleep latency and stage 2 of non-rapid eye movement sleep compared with non-thalamus infarction group. The prevalence of SD was relatively high in acute cerebral infarction patients, and the detailed classification of acute cerebral infarction may provide a more effective therapeutic method and therefore relieve patients' pain and supply a better quality of sleep. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Cytochrome c Maturation and the Physiological Role of c-Type Cytochromes in Vibrio cholerae

    PubMed Central

    Braun, Martin; Thöny-Meyer, Linda

    2005-01-01

    Vibrio cholerae lives in different habitats, varying from aquatic ecosystems to the human intestinal tract. The organism has acquired a set of electron transport pathways for aerobic and anaerobic respiration that enable adaptation to the various environmental conditions. We have inactivated the V. cholerae ccmE gene, which is required for cytochrome c biogenesis. The resulting strain is deficient of all c-type cytochromes and allows us to characterize the physiological role of these proteins. Under aerobic conditions in rich medium, V. cholerae produces at least six c-type cytochromes, none of which is required for growth. Wild-type V. cholerae produces active fumarate reductase, trimethylamine N-oxide reductase, cbb3 oxidase, and nitrate reductase, of which only the fumarate reductase does not require maturation of c-type cytochromes. The reduction of nitrate in the medium resulted in the accumulation of nitrite, which is toxic for the cells. This suggests that V. cholerae is able to scavenge nitrate from the environment only in the presence of other nitrite-reducing organisms. The phenotypes of cytochrome c-deficient V. cholerae were used in a transposon mutagenesis screening to search for additional genes required for cytochrome c maturation. Over 55,000 mutants were analyzed for nitrate reductase and cbb3 oxidase activity. No transposon insertions other than those within the ccm genes for cytochrome c maturation and the dsbD gene, which encodes a disulphide bond reductase, were found. In addition, the role of a novel CcdA-like protein in cbb3 oxidase assembly is discussed. PMID:16109941

  6. Posaconazole responsive cerebral aspergillosis in an immunocompetent adult.

    PubMed

    Ellenbogen, Jonathan Richard; Waqar, Mueez; Denning, David W; Cooke, Richard P D; Skinner, Derek W; Lesser, Tristram; Javadpour, Mohsen

    2014-10-01

    Cerebral aspergillosis is a rare manifestation of invasive aspergillosis that usually affects immunocompromised patients. There are few treatment options for recurrent disease and experiences with immunocompetent patients are lacking. We report the clinical course of an immunocompetent patient with recurrent cerebral aspergillosis, following initial treatment with burr hole aspiration and voriconazole, who showed remarkable response to posaconazole. The patient remains clinically well with no evidence of recurrence on MRI 7 years following diagnosis. To our knowledge this is the first reported experience with posaconazole in an immunocompetent patient with cerebral aspergillosis.

  7. [Physiopathology of ocular movements in infantile cerebral paralysis].

    PubMed

    Escobar, R; Ronquillo, A; Escobar, F; Alvarez-Morujo, M

    1989-01-01

    Cerebral palsy is a permanent and non-progressive brain damage due to various causes affecting a child from the intrauterine life up to the first two years of life. Its most common cause is neonatal hypoxic encephalopathy. The cerebral damage is diffuse so that it is commonly associated with epilepsy, mental retardation, dysarthria, hearing loss and oculomotor abnormalities. Strabismus is found in 50% of children with cerebral palsy. This prevalence is significantly different from the 2% incidence of oculomotor abnormalities in the pre-school age, it is noteworthy that strabismus and refractive errors respond to the classical therapeutic measures.

  8. Role of cytochrome P450 in drug interactions.

    PubMed

    Bibi, Zakia

    2008-10-18

    Drug-drug interactions have become an important issue in health care. It is now realized that many drug-drug interactions can be explained by alterations in the metabolic enzymes that are present in the liver and other extra-hepatic tissues. Many of the major pharmacokinetic interactions between drugs are due to hepatic cytochrome P450 (P450 or CYP) enzymes being affected by previous administration of other drugs. After coadministration, some drugs act as potent enzyme inducers, whereas others are inhibitors. However, reports of enzyme inhibition are very much more common. Understanding these mechanisms of enzyme inhibition or induction is extremely important in order to give appropriate multiple-drug therapies. In future, it may help to identify individuals at greatest risk of drug interactions and adverse events.

  9. Role of cytochrome P450 in drug interactions

    PubMed Central

    Bibi, Zakia

    2008-01-01

    Drug-drug interactions have become an important issue in health care. It is now realized that many drug-drug interactions can be explained by alterations in the metabolic enzymes that are present in the liver and other extra-hepatic tissues. Many of the major pharmacokinetic interactions between drugs are due to hepatic cytochrome P450 (P450 or CYP) enzymes being affected by previous administration of other drugs. After coadministration, some drugs act as potent enzyme inducers, whereas others are inhibitors. However, reports of enzyme inhibition are very much more common. Understanding these mechanisms of enzyme inhibition or induction is extremely important in order to give appropriate multiple-drug therapies. In future, it may help to identify individuals at greatest risk of drug interactions and adverse events. PMID:18928560

  10. Unusual Cytochrome P450 Enzymes and Reactions*

    PubMed Central

    Guengerich, F. Peter; Munro, Andrew W.

    2013-01-01

    Cytochrome P450 enzymes primarily catalyze mixed-function oxidation reactions, plus some reductions and rearrangements of oxygenated species, e.g. prostaglandins. Most of these reactions can be rationalized in a paradigm involving Compound I, a high-valent iron-oxygen complex (FeO3+), to explain seemingly unusual reactions, including ring couplings, ring expansion and contraction, and fusion of substrates. Most P450s interact with flavoenzymes or iron-sulfur proteins to receive electrons from NAD(P)H. In some cases, P450s are fused to protein partners. Other P450s catalyze non-redox isomerization reactions. A number of permutations on the P450 theme reveal the diversity of cytochrome P450 form and function. PMID:23632016

  11. Distal anterior cerebral artery aneurysms.

    PubMed

    Lehecka, Martin; Dashti, Reza; Lehto, Hanna; Kivisaari, Riku; Niemelä, Mika; Hernesniemi, Juha

    2010-01-01

    Distal anterior cerebral artery (DACA) aneurysms, also known as pericallosal artery aneurysms, represent about 6% of all intracranial aneurysms. They are located on the A2-A5 segments of the anterior cerebral artery and on its distal branches. This paper summarizes present knowledge on radiological features, treatment options, treatment results, and long-term follow-up of DACA aneurysms. Typical features of DACA aneurysms are small size, broad base, and branches originating from the base. When ruptured, they cause intracerebral hematoma in nearly half of the cases. DACA aneurysms are nowadays more often treated with microsurgical clipping than endovascular coiling due to their distal location and morphologic features. With clipping the results are same or slightly better than for aneurysms at other locations, coiling is often associated with more complications than in other aneurysms. Clipping is a long-lasting treatment with very small recurrence rate, there is no long-term data available on efficacy of coiling yet. For ruptured DACA aneurysms the most important factors affecting outcome is the severity of initial bleeding and patient's age.

  12. Cerebral oxygenation following epinephrine infusion.

    PubMed

    Steinback, Craig D; Zubin, Petra; Breskovic, Toni; Bakovic, Darija; Pivac, Nediljko; Dujic, Zeljko

    2012-10-15

    Evidence suggests that the autonomic nervous system may actively regulate the cerebral vasculature. In this study, central hemodynamics and brain oxy-hemoglobin, deoxy-hemoglobin and total hemoglobin changes (bO₂Hb, bdHb and bTHb) were monitored during infusion of epinephrine (0.06 μg/kg/min over 6 min, and 0.12 μg/kg/min for 3 min) in 12 men. Epinephrine decreased mean arterial pressure (MAP) and total peripheral resistance (TPR), while heart rate (HR), stroke volume (SV) and cardiac output (CO) increased, but did not affect bO₂Hb, bdHb or bTHb. However, upon the cessation of epinephrine infusion an increase in both Oxy- and Total Hb occurred which peaked at 3 min post infusion (+6.0±4.6 and +4.9±4.8 μmol/L respectively, P<0.05) and persisted for 20 min post infusion (+1.5±2.2 and +1.8±2.7 μmol/L respectively, P<0.05). No evidence was found for reduction in cerebral oxygenation during a cold-pressor test. The results of the present study demonstrated that clinical doses of epinephrine result in a delayed increase in cortical blood volume due to an increase in Oxy-Hb, consistent with vasodilation.

  13. Early evolution of cytochrome bc complexes.

    PubMed

    Schütz, M; Brugna, M; Lebrun, E; Baymann, F; Huber, R; Stetter, K O; Hauska, G; Toci, R; Lemesle-Meunier, D; Tron, P; Schmidt, C; Nitschke, W

    2000-07-21

    Primary structures, functional characteristics and phylogenetic relationships of subunits of cytochrome bc complexes from phylogenetically diverse bacterial and archaeal species were analysed. A single case of lateral gene transfer, i.e. the import of an epsilon-proteobacterial cytochrome bc(1) complex into Aquificales, was identified. For the enzyme in the remainder of the species studied, the obtained phylogenies were globally in line with small subunit rRNA trees. The distribution of a few key phylogenetic markers, such as contiguousness of cytochrome b, nature of the c-type subunit or spacing between b-heme ligands, are discussed. A localised modification of previous tree topologies is proposed on the basis of the obtained data. The comparison of extant enzymes furthermore allowed us to define the minimal functional and evolutionary core of the enzyme. The data furthermore suggest that the ancestral enzyme was put together from subunits that previously had played a role in other electron transfer chains. Copyright 2000 Academic Press.

  14. Maternal inheritance of cytochrome f in interspecific Nicotiana hybrids.

    PubMed

    Gray, J C

    1980-11-01

    Cytochrome f has been purified to homogeneity, as judged by polyacrylamide gel electrophoresis, from the leaves of Nicotiana tabacum, Nicotiana glutinosa and their reciprocal hybrids. The cytochrome was extracted from chloroplast membranes by sonication in 2% Triton X-100 and 4M urea and was subsequently purified by acetone precipitation and chromatography on Ultrogel AcA 22 in the presence of cholate and on Sephadex G-200 in the presence of sodium dodecylsulphate. The purified cytochrome had a molecular weight of 32,700 determined by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulphate. A difference in the primary structure of cytochrome f from N. tabacum and N. glutinosa was detected by ion-exchange chromatography of the products of trypsin hydrolysis. Cytochrome f from N. tabacum contained an additional peptide not present in the cytochrome fom N. glutinosa. This additional peptide was present in the cytochrome from N. tabacum female x N. glutinosa male, but not in the cytochrome from N. glutinosa female x N. tabacum male, indicating a maternal mode of inheritance of the primary structure of cytochrome f. This suggests an extranuclear, probably chloroplast, location for the genetic information for cytochrome f.

  15. [Cerebral ischemia and histamine].

    PubMed

    Adachi, Naoto

    2002-10-01

    Cerebral ischemia induces excess release of glutamate and an increase in the intracellular Ca2+ concentration, which provoke catastrophic enzymatic processes leading to irreversible neuronal injury. Histamine plays the role of neurotransmitter in the central nervous system, and histaminergic fibers are widely distributed in the brain. In cerebral ischemia, release of histamine from nerve endings has been shown to be enhanced by facilitation of its activity. An inhibition of the histaminergic activity in ischemia aggravates the histologic outcome. In contrast, intracerebroventricular administration of histamine improves the aggravation, whereas blockade of histamine H2 receptors aggravates ischemic injury. Furthermore, H2 blockade enhances ischemic release of glutamate and dopamine. These findings suggest that central histamine provides beneficial effects against ischemic neuronal damage by suppressing release of excitatory neurotransmitters. However, histaminergic H2 action facilitates the permeability of the blood-brain barrier and shows deleterious effects on cerebral edema.

  16. Hypernatraemia in cerebral disorders

    PubMed Central

    Taylor, W. H.

    1962-01-01

    Six patients are described in whom cerebral damage was associated with raised plasma sodium and chloride concentrations and with extremely low urinary outputs of sodium and chloride. The patients were not clinically dehydrated and direct determinations showed that the blood and plasma volumes, the endogenous creatinine clearance, and the urinary output of antidiuretic hormone were normal. For these and other reasons it is concluded that the metabolic picture results not from diminished circulatory volume, water deficiency, sodium deficiency, undetected diabetes insipidus or osmotic diuresis, but from the cerebral damage itself. In these and other cited cases, the cerebral damage was localized chiefly in the frontal lobes, hypothalamus or lower brain-stem, thus suggesting a descending pathway, the relationship of which to the pineal area controlling aldosterone secretion requires clarification. Images PMID:13920001

  17. Duplicated middle cerebral artery.

    PubMed

    Perez, Jesus; Machado, Calixto; Scherle, Claudio; Hierro, Daniel

    2009-01-01

    Duplicated middle cerebral artery (DMCA) is an anomalous vessel arising from the internal carotid artery. The incidence DMCA is relatively law, and an association between this anomaly and cerebral aneurysms has been documented. There is a controversy whether DMCA may have perforating arteries. This is an important fact to consider in aneurysm surgery. We report the case of a 34-year-old black woman who suffered a subarachnoid hemorrhage and the angiography a left DMCA, and an aneurysm in an inferior branch of the main MCA. The DMCA and the MCA had perforating arteries. The aneurysm was clipped without complications. The observation of perforating arteries in our patient confirms that the DMCA may have perforating arteries. This is very important to be considered in cerebral aneurysms surgery. Moreover, the DMCA may potentially serve as a collateral blood supply to the MCA territory in cases of MCA occlusion.

  18. VDAC regulates AAC-mediated apoptosis and cytochrome c release in yeast

    PubMed Central

    Trindade, Dário; Pereira, Clara; Chaves, Susana R.; Manon, Stéphen; Côrte-Real, Manuela; Sousa, Maria J.

    2016-01-01

    Mitochondrial outer membrane permeabilization is a key event in apoptosis processes leading to the release of lethal factors. We have previously shown that absence of the ADP/ATP carrier (AAC) proteins (yeast orthologues of mammalian ANT proteins) increased the resistance of yeast cells to acetic acid, preventing MOMP and the release of cytochrome c from mitochondria during acetic acid - induced apoptosis. On the other hand, deletion of POR1 (yeast voltage-dependent anion channel - VDAC) increased the sensitivity of yeast cells to acetic acid. In the present work, we aimed to further characterize the role of yeast VDAC in acetic acid - induced apoptosis and assess if it functionally interacts with AAC proteins. We found that the sensitivity to acetic acid resulting from POR1 deletion is completely abrogated by the absence of AAC proteins, and propose that Por1p acts as a negative regulator of acetic acid - induced cell death by a mechanism dependent of AAC proteins, by acting on AAC - dependent cytochrome c release. Moreover, we show that Por1p has a role in mitochondrial fusion that, contrary to its role in apoptosis, is not affected by the absence of AAC, and demonstrate that mitochondrial network fragmentation is not sufficient to induce release of cytochrome c or sensitivity to acetic acid - induced apoptosis. This work enhances our understanding on cytochrome c release during cell death, which may be relevant in pathological scenarios where MOMP is compromised. PMID:28357318

  19. Paracoccus denitrificans cytochrome c oxidase: a kinetic study on the two- and four-subunit complexes.

    PubMed

    Nicoletti; Witt; Ludwig; Brunori; Malatesta

    1998-07-20

    Cytochrome c oxidase from Paracoccus denitrificans has been purified in two different forms differing in polypeptide composition. An enzyme containing polypeptides I-IV is obtained when the purification procedure is performed in beta-d-dodecylmaltoside. If, however, Triton X-100 is used to purify the enzyme under otherwise identical conditions, an enzyme is obtained containing only subunits I-II. The two enzymes are undistinguishable by optical spectroscopy but show significant differences in the transient and steady-state time regimes, as studied by stopped-flow spectroscopy. The observed differences, however, are not due to removal of subunits III and IV, but rather to a specific effect of Triton X-100 which appears to affect cytochrome c binding. From these results it is not expected that subunits III and IV play any significant role in cytochrome c binding and, possibly, in the subsequent electron transfer processes. The results also suggest that both electrostatic and hydrophobic interactions may be important in the initial electron transfer process from cytochrome c.

  20. Role of Bradyrhizobium japonicum cytochrome c550 in nitrite and nitrate respiration.

    PubMed

    Bueno, Emilio; Bedmar, Eulogio J; Richardson, David J; Delgado, María J

    2008-02-01

    Bradyrhizobium japonicum cytochrome c(550), encoded by cycA, has been previously suggested to play a role in denitrification, the respiratory reduction of nitrate to dinitrogen. However, the exact role of this cytochrome in the denitrification process is unknown. This study shows that cytochrome c(550) is involved in electron transfer to the copper-containing nitrite reductase of B. japonicum, as revealed by the inability of a cycA mutant strain to consume nitrite and, consequently, to grow under denitrifying conditions with nitrite as the electron acceptor. Mutation of cycA had no apparent effect on methylviologen-dependent nitrite reductase activity. However, succinate-dependent nitrite reduction was largely inhibited, suggesting that c(550) is the in vivo electron donor to copper-containing nitrite reductase. In addition, this study demonstrates that a cytochrome c(550) mutation has a negative effect on expression of the periplasmic nitrate reductase. This phenotype can be rescued by extending the growth period of the cells. A model is proposed whereby a mutation in cycA reduces expression of the cbb(3)-type oxidase, affecting oxygen consumption rate by the cells and consequently preventing maximal expression of the periplasmic nitrate reductase during the first days of the growth period.

  1. Cerebral venous sinus thrombosis with cerebral hemorrhage during early pregnancy

    PubMed Central

    Nie, Quanmin; Guo, Pin; Ge, Jianwei; Qiu, Yongming

    2015-01-01

    Cerebral venous sinus thrombosis (CVST) rarely induces cerebral hemorrhage, and CVST with cerebral hemorrhage during early pregnancy is extremely rare. Upon literature review, we are able to find only one case of CVST with cerebral hemorrhage in early pregnancy. In this paper, we report another case of a 27-year-old patient who developed CVST with cerebral hemorrhage in her fifth week of pregnancy. Although the optimal treatment for this infrequent condition remains controversial, we adopted anticoagulation as the first choice of treatment and obtained favorable results. PMID:25630781

  2. Impaired cerebral autoregulation in obstructive sleep apnea.

    PubMed

    Urbano, Fred; Roux, Francoise; Schindler, Joseph; Mohsenin, Vahid

    2008-12-01

    Obstructive sleep apnea (OSA) increases the risk of stroke independent of known vascular and metabolic risk factors. Although patients with OSA have higher prevalence of hypertension and evidence of hypercoagulability, the mechanism of this increased risk is unknown. Obstructive apnea events are associated with surges in blood pressure, hypercapnia, and fluctuations in cerebral blood flow. These perturbations can adversely affect the cerebral circulation. We hypothesized that patients with OSA have impaired cerebral autoregulation, which may contribute to the increased risk of cerebral ischemia and stroke. We examined cerebral autoregulation in patients with and without OSA by measuring cerebral artery blood flow velocity (CBFV) by using transcranial Doppler ultrasound and arterial blood pressure using finger pulse photoplethysmography during orthostatic hypotension and recovery as well as during 5% CO(2) inhalation. Cerebral vascular conductance and reactivity were determined. Forty-eight subjects, 26 controls (age 41.0+/-2.3 yr) and 22 OSA (age 46.8+/-2.3 yr) free of cerebrovascular and active coronary artery disease participated in this study. OSA patients had a mean apnea-hypopnea index of 78.4+/-7.1 vs. 1.8+/-0.3 events/h in controls. The oxygen saturation during sleep was significantly lower in the OSA group (78+/-2%) vs. 91+/-1% in controls. The dynamic vascular analysis showed mean CBFV was significantly lower in OSA patients compared with controls (48+/-3 vs. 55+/-2 cm/s; P <0.05, respectively). The OSA group had a lower rate of recovery of cerebrovascular conductance for a given drop in blood pressure compared with controls (0.06+/-0.02 vs. 0.20+/-0.06 cm.s(-2).mmHg(-1); P <0.05). There was no difference in cerebrovascular vasodilatation in response to CO(2). The findings showed that patients with OSA have decreased CBFV at baseline and delayed cerebrovascular compensatory response to changes in blood pressure but not to CO(2). These perturbations may

  3. Cytochrome cbb3 of Thioalkalivibrio is a Na+-pumping cytochrome oxidase

    PubMed Central

    Muntyan, Maria S.; Cherepanov, Dmitry A.; Malinen, Anssi M.; Bloch, Dmitry A.; Sorokin, Dimitry Y.; Severina, Inna I.; Ivashina, Tatiana V.; Lahti, Reijo; Muyzer, Gerard; Skulachev, Vladimir P.

    2015-01-01

    Cytochrome c oxidases (Coxs) are the basic energy transducers in the respiratory chain of the majority of aerobic organisms. Coxs studied to date are redox-driven proton-pumping enzymes belonging to one of three subfamilies: A-, B-, and C-type oxidases. The C-type oxidases (cbb3 cytochromes), which are widespread among pathogenic bacteria, are the least understood. In particular, the proton-pumping machinery of these Coxs has not yet been elucidated despite the availability of X-ray structure information. Here, we report the discovery of the first (to our knowledge) sodium-pumping Cox (Scox), a cbb3 cytochrome from the extremely alkaliphilic bacterium Thioalkalivibrio versutus. This finding offers clues to the previously unknown structure of the ion-pumping channel in the C-type Coxs and provides insight into the functional properties of this enzyme. PMID:26056262

  4. Functional coadaptation between cytochrome c and cytochrome c oxidase within allopatric populations of a marine copepod.

    PubMed

    Rawson, Paul D; Burton, Ronald S

    2002-10-01

    Geographically isolated populations may accumulate alleles that function well on their own genetic backgrounds but poorly on the genetic backgrounds of other populations. Consequently, interpopulation hybridization may produce offspring of low fitness as a result of incompatibilities arising in allopatry. Genes participating in these epistatic incompatibility systems remain largely unknown. In fact, despite the widely recognized importance of epistatic interactions among gene products, few data directly address the functional consequences of such interactions among natural genetic variants. In the marine copepod, Tigriopus californicus, we found that the cytochrome c variants isolated from two different populations each had significantly higher activity with the cytochrome c oxidase derived from their respective source population. Three amino acid substitutions in the cytochrome c protein appear to be sufficient to confer population specificity. These results suggest that electron transport system (ETS) proteins form coadapted sets of alleles within populations and that disruption of the coadapted ETS gene complex leads to functional incompatibilities that may lower hybrid fitness.

  5. [Cerebral hemorrhage associated with the use phenylpropanolamine].

    PubMed

    Barinagarrementería, F; Méndez, A; Vega, F

    1990-10-01

    Phenylpropanolamine is a sympatheticomimetic agent which is widely used in pharmacologic preparations to treat nasal congestion, and to produce and anorexigenic or stimulant action. In the last years complications affecting the nervous system or the general condition have been reported. There is still controversy with regard to the safety of this pharmacologic agent. In this study we report two cases of parenchymal cerebral hemorrhage secondary to phenylpropanolamine administration. In the second case we observed angiographic findings of a reversible vasculopathy.

  6. Lever arm dysfunction in cerebral palsy gait.

    PubMed

    Theologis, Tim

    2013-11-01

    Skeletal structures act as lever arms during walking. Muscle activity and the ground reaction against gravity exert forces on the skeleton, which generate torque (moments) around joints. These lead to the sequence of movements which form normal human gait. Skeletal deformities in cerebral palsy (CP) affect the function of bones as lever arms and compromise gait. Lever arm dysfunction should be carefully considered when contemplating treatment to improve gait in children with CP.

  7. Neonatal intensive care: an obvious, yet difficult area for cerebral near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Skov, Lotte; Brun, Nikolai C.; Greisen, Gorm

    1997-01-01

    The first clinical application of near-infrared spectroscopy (NIRS) 11 years go was on the head of newborn infants under intensive care. Since then much credible and some important data have been accumulated in this area of research. The best data have been obtained using manipulation of arterial oxygen saturation to obtain single or repeated estimates of cerebral blood flow or cerebral blood volume, or interference with cerebral venous return to obtain measures of venous oxygen saturation. It has been more difficult to take advantage of the continuous and noninvasive nature of NIRS. In particular, the value of the cytochrome signal can still be doubted. A role has not yet developed for NIRS in clinical neonatology.

  8. Cerebral oxygen metabolism and blood flow in human cerebral ischemic infarction

    SciTech Connect

    Lenzi, G.L.; Frackowiak, R.S.; Jones, T.

    1982-09-01

    Fifteen patients with acute cerebral hemispheric infarcts have been studied with positron emission tomography and the /sup 15/O steady-state inhalation technique. Thirteen follow-up studies were also performed. The values of cerebral oxygen metabolism (CMRO/sub 2/), cerebral blood flow (CBF), and oxygen extraction ration (OER) have been calculated for the infarcted regions, their borders, the symmetrical regions in contralateral cerebral hemispheres, and the cerebellar hemispheres. This study demonstrates that in the completed stroke there are thresholds for regional CMRO/sub 2/ and regional CBF below which the general clinical outcome of the patients is usually poor. The ischaemic lesions invariably produce an uncoupling between the greatly decreased metabolic demand and the less affected blood supply, with very frequent instances of relative hyperperfusion. Remote effects of the hemispheric infarcts have been demonstrated, such as crossed cerebellar diaschisis and contralateral transhemispheric depression. The level of consciousness correlates with oxygen uptake and blood flow both in the posterior fossa and in the contralateral cerebral hemispheres. The follow-up studies of individual patients underline the high variability of metabolism-to-flow balance during the acute phase of the illness, and stress the need for more studies focused on repeated assessments of homogeneous patient populations.

  9. Current proceedings of cerebral palsy.

    PubMed

    Fan, Hueng-Chuen; Ho, Li-Ing; Chi, Ching-Shiang; Cheng, Shin-Nan; Juan, Chun-Jung; Chiang, Kuo-Liang; Lin, Shinn-Zong; Harn, Horng-Jyh

    2015-01-01

    Cerebral palsy (CP) is a complicated disease with varying causes and outcomes. It has created significant burden to both affected families and societies, not to mention the quality of life of the patients themselves. There is no cure for the disease; therefore, development of effective therapeutic strategies is in great demand. Recent advances in regenerative medicine suggest that the transplantation of stem cells, including embryonic stem cells, neural stem cells, bone marrow mesenchymal stem cells, induced pluripotent stem cells, umbilical cord blood cells, and human embryonic germ cells, focusing on the root of the problem, may provide the possibility of developing a complete cure in treating CP. However, safety is the first factor to be considered because some stem cells may cause tumorigenesis. Additionally, more preclinical and clinical studies are needed to determine the type of cells, route of delivery, cell dose, timing of transplantation, and combinatorial strategies to achieve an optimal outcome.

  10. [Unilateral spastic cerebral palsy (hemiparesis)].

    PubMed

    Senst, S

    2014-07-01

    Approximately 33 % of spastic movement disorders are due to unilateral spastic cerebral palsy which is characterized by a one-sided motor movement disorder which has a correlative in focal contralateral brain injury. The upper extremities are more severely affected so that ambulatory movement is nearly always possible. The development is substantially influenced by epilepsy and perception disturbances. Therefore, an interdisciplinary team is necessary for optimal therapy. In addition to physiotherapy and ergotherapy, orthopedic technicians, orthopedic and hand surgeons in particular are also required. The different classifications and therapy approaches are described By orthopedic and hand surgical interventions flexible and structural alterations can be improved but a normalization of arm and leg functions is not possible. The prognosis in the presence of dystonia and ataxia is particularly unfavorable.

  11. The cytochrome c peroxidase and cytochrome c encounter complex: the other side of the story.

    PubMed

    Schilder, Jesika; Löhr, Frank; Schwalbe, Harald; Ubbink, Marcellus

    2014-05-21

    Formation of an encounter complex is important for efficient protein complex formation. The encounter state consists of an ensemble of orientations of two proteins in the complex. Experimental description of such ensembles inherently suffers from insufficient data availability. We have measured paramagnetic relaxation enhancements (PRE) on cytochrome c peroxidase (CcP) caused by its partner cytochrome c (Cc) carrying a spin label. The data complement earlier PRE data of spin labelled CcP, identifying several new interactions. This work demonstrates the need of obtaining as many independent data sets as possible to achieve the most accurate description of an encounter complex.

  12. Marked and variable inhibition by chemical fixation of cytochrome oxidase and succinate dehydrogenase in single motoneurons

    NASA Technical Reports Server (NTRS)

    Chalmers, G. R.; Edgerton, V. R.

    1989-01-01

    The effect of tissue fixation on succinate dehydrogenase and cytochrome oxidase activity in single motoneurons of the rat was demonstrated using a computer image processing system. Inhibition of enzyme activity by chemical fixation was variable, with some motoneurons being affected more than others. It was concluded that quantification of enzymatic activity in chemically fixed tissue provides an imprecise estimate of enzyme activities found in fresh-frozen tissues.

  13. Marked and variable inhibition by chemical fixation of cytochrome oxidase and succinate dehydrogenase in single motoneurons

    NASA Technical Reports Server (NTRS)

    Chalmers, G. R.; Edgerton, V. R.

    1989-01-01

    The effect of tissue fixation on succinate dehydrogenase and cytochrome oxidase activity in single motoneurons of the rat was demonstrated using a computer image processing system. Inhibition of enzyme activity by chemical fixation was variable, with some motoneurons being affected more than others. It was concluded that quantification of enzymatic activity in chemically fixed tissue provides an imprecise estimate of enzyme activities found in fresh-frozen tissues.

  14. Biogenesis of cytochrome b6 in photosynthetic membranes.

    PubMed

    Saint-Marcoux, Denis; Wollman, Francis-André; de Vitry, Catherine

    2009-06-29

    In chloroplasts, binding of a c'-heme to cytochrome b(6) on the stromal side of the thylakoid membranes requires a specific mechanism distinct from the one at work for c-heme binding to cytochromes f and c(6) on the lumenal side of membranes. Here, we show that the major protein components of this pathway, the CCBs, are bona fide transmembrane proteins. We demonstrate their association in a series of hetero-oligomeric complexes, some of which interact transiently with cytochrome b(6) in the process of heme delivery to the apoprotein. In addition, we provide preliminary evidence for functional assembly of cytochrome b(6)f complexes even in the absence of c'-heme binding to cytochrome b(6). Finally, we present a sequential model for apo- to holo-cytochrome b(6) maturation integrated within the assembly pathway of b(6)f complexes in the thylakoid membranes.

  15. Biogenesis of cytochrome b6 in photosynthetic membranes

    PubMed Central

    Saint-Marcoux, Denis; Wollman, Francis-André

    2009-01-01

    In chloroplasts, binding of a c′-heme to cytochrome b6 on the stromal side of the thylakoid membranes requires a specific mechanism distinct from the one at work for c-heme binding to cytochromes f and c6 on the lumenal side of membranes. Here, we show that the major protein components of this pathway, the CCBs, are bona fide transmembrane proteins. We demonstrate their association in a series of hetero-oligomeric complexes, some of which interact transiently with cytochrome b6 in the process of heme delivery to the apoprotein. In addition, we provide preliminary evidence for functional assembly of cytochrome b6f complexes even in the absence of c′-heme binding to cytochrome b6. Finally, we present a sequential model for apo- to holo-cytochrome b6 maturation integrated within the assembly pathway of b6f complexes in the thylakoid membranes. PMID:19564403

  16. Twin Studies in Brazil: Projects and Plans / Twin Research: Infant Twins' Viewing of Social Scenes; Religiosity and Substance Abuse; Down Syndrome Among Twins; Twin Case of Chronic Periodontitis / In the News: The Twin 'Property Brothers', Twins With Cerebral Palsy; Twins Affected With the Zika Virus; Twin Writers Derek and Roddy; Twins on Sports Teams; Local Quads.

    PubMed

    Segal, Nancy L

    2017-10-01

    Twin research in Brazil twin has expanded enormously in recent years, engaging the interests and efforts of many investigators, students and twins. Descriptions and brief summaries of this work and talks given by investigators at local conferences are presented, based on my four-city lecture tour. This is followed by summaries of twin research on infants' viewing of social scenes, religiosity and substance abuse, Down syndrome, and chronic periodontitis. This article concludes with twin-related news and information of general interest, including identical twin property designers, twins with cerebral palsy, twins affected with the Zika virus, a pair of twin writers, twins in sports, and a set of quadruplets from my childhood neighborhood in Riverdale, New York.

  17. Observations on iron uptake, iron metabolism, cytochrome c content, cytochrome a content and cytochrome c-oxidase activity in regenerating rat liver.

    PubMed

    Gear, A R

    1965-11-01

    1. Differential and density-gradient centrifugation were used to fractionate mitochondria and fluffy layer from normal and regenerating rat liver. The iron, cytochrome a and cytochrome c contents and cytochrome c-oxidase activity were studied as well as the uptake of (59)Fe into protein and cytochrome c. 2. A certain degree of heterogeneity was evident between the heavy-mitochondrial and light-mitochondrial fractions, and in their behaviour during liver regeneration. 3. The specific content of light-mitochondrial iron and cytochrome a was 1.3-1.4 times that of heavy mitochondria. Changes in cytochrome c-oxidase activity closely followed those of cytochrome a content during liver regeneration, but not for light mitochondria after 10 days. 4. Radioactive iron ((59)Fe) was most actively taken up by well-washed light mitochondria during early liver regeneration. After 22 days fluffy layer became preferentially labelled. This substantiates the view that fluffy layer partially represents broken-down mitochondria. 5. During early regeneration, light-mitochondrial fractions separated along a density gradient were about 3 times as radioactive, and showed distinct heterogeneity of (59)Fe-labelling, in contrast with near homogeneity for heavy mitochondria. 6. Immediately after partial hepatectomy fractions corresponding to density 1.155 were 5-10 times as radioactive as particles of greater density. The radioactivity decreased sharply after 6 days. 7. These particles of low density possessed higher NADH-cytochrome c-reductase (1.5-5-fold) and succinate-dehydrogenase (1.1-2-fold) activities than typical mitochondrial fractions. Their succinate-cytochrome c-reductase and cytochrome c-oxidase activities were slightly lower. 8. The results are discussed in relation to mitochondrial morphogenesis, and a possible route from submitochondrial particles is suggested.

  18. Observations on iron uptake, iron metabolism, cytochrome c content, cytochrome a content and cytochrome c-oxidase activity in regenerating rat liver

    PubMed Central

    Gear, A. R. L.

    1965-01-01

    1. Differential and density-gradient centrifugation were used to fractionate mitochondria and fluffy layer from normal and regenerating rat liver. The iron, cytochrome a and cytochrome c contents and cytochrome c-oxidase activity were studied as well as the uptake of 59Fe into protein and cytochrome c. 2. A certain degree of heterogeneity was evident between the heavy-mitochondrial and light-mitochondrial fractions, and in their behaviour during liver regeneration. 3. The specific content of light-mitochondrial iron and cytochrome a was 1·3–1·4 times that of heavy mitochondria. Changes in cytochrome c-oxidase activity closely followed those of cytochrome a content during liver regeneration, but not for light mitochondria after 10 days. 4. Radioactive iron (59Fe) was most actively taken up by well-washed light mitochondria during early liver regeneration. After 22 days fluffy layer became preferentially labelled. This substantiates the view that fluffy layer partially represents broken-down mitochondria. 5. During early regeneration, light-mitochondrial fractions separated along a density gradient were about 3 times as radioactive, and showed distinct heterogeneity of 59Fe-labelling, in contrast with near homogeneity for heavy mitochondria. 6. Immediately after partial hepatectomy fractions corresponding to density 1·155 were 5–10 times as radioactive as particles of greater density. The radioactivity decreased sharply after 6 days. 7. These particles of low density possessed higher NADH–cytochrome c-reductase (1·5–5-fold) and succinate-dehydrogenase (1·1–2-fold) activities than typical mitochondrial fractions. Their succinate–cytochrome c-reductase and cytochrome c-oxidase activities were slightly lower. 8. The results are discussed in relation to mitochondrial morphogenesis, and a possible route from submitochondrial particles is suggested. PMID:16749160

  19. The effect of neuraxial anesthesia on maternal cerebral hemodynamics.

    PubMed

    Postma, Ineke R; van Veen, Teelkien R; Mears, Scott L; Zeeman, Gerda G; Haeri, Sina; Belfort, Michael A

    2014-10-01

    Neuraxial anesthesia is known to reduce sympathetic tone and mean arterial pressure. Effects on cerebral hemodynamics in pregnancy are not well known. We hypothesize that cerebral hemodynamic parameters will change with respect to baseline following regional analgesia/anesthesia. We performed maternal transcranial Doppler of the middle cerebral artery in 20 women receiving epidural analgesia for labor, and 18 undergoing spinal anesthesia for cesarean section at baseline, 5 and 15 minutes. Systemic blood pressure (BP), systolic/diastolic/mean velocity, resistance and pulsatility index (PI) were recorded. Cerebral perfusion pressure, critical closing pressure (CrCP), resistance area product, and cerebral flow index were calculated. Epidural placement was associated with significant decreases in systolic/diastolic BP/mean velocity/CrCP after 15 minutes, with a corresponding increase in PI. In the spinal group, systolic/diastolic BP/mean velocity uniformly decreased and remained low after 15 minutes, and PI significantly increased and remained constant after 15 minutes. No differences were seen in BP or cerebral hemodynamics between the groups. This study demonstrates that both epidural analgesia and spinal anesthesia result in measurable cerebral hemodynamic changes in normotensive term pregnancy that are likely to be clinically insignificant as they do not affect perfusion pressure or flow. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  20. Stimulation of cellular XTT reduction by cytochrome oxidase inhibitors.

    PubMed

    Kunimoto, S; Nosaka, C; Takeuchi, T

    1999-06-01

    XTT reducing activity by CHO and L1210 cells was found to be stimulated by the presence of cytochrome oxidase inhibitors such as NaN3 or KCN. Among the other respiratory chain inhibitors, antimycin A (a complex III inhibitor) and chlorpromazine inhibited cellular XTT reduction, and rotenone and malonate showed slight inhibition and no effect, respectively. It is suggested that XTT reduction is coupled with the respiratory chain via cytochrome c, which is located between complexes III and IV (cytochrome oxidase).

  1. Spectral and potentiometric analysis of cytochromes from Bacillus subtilis.

    PubMed

    de Vrij, W; van den Burg, B; Konings, W N

    1987-08-03

    Bacillus subtilis cytoplasmic membranes contain several cytochromes which are linked to the respiratory chain. At least six different cytochromes have been separated and identified by ammonium sulphate fractionation and ion-exchange chromatography. They include two terminal oxidases with CO-binding properties and cyanide sensitivity. One of these is an aa3-type cytochrome c oxidase which has characteristic absorption maxima in the reduced-oxidized difference spectrum at 601 nm in the alpha-band and at 443 nm in the Soret band regions. In the alpha-band two separate electron transitions with Em = +205 mV and Em = +335 mV can be discriminated by redox potentiometric titration. The other CO-binding cytochrome c oxidase contains two cytochrome b components with alpha-band maxima at 556 nm and 559 nm. Cytochrome b556 can be reduced by ascorbate and has an Em + +215 mV, whereas cytochrome b559 has an Em = +140 mV. Furthermore a complex consisting of a cytochrome b564 (Em = +140 mV) associated with a cytochrome c554 (Em = +250 mV) was found. This cytochrome c554, which can be reduced by ascorbate, appears to have an asymmetrical alpha-peak and stains for heme-catalyzed peroxidase activity on SDS-containing polyacrylamide gels. A protein with a molecular mass of about 30 kDa is responsible for this activity. A cytochrome b559 (Em = +65 mV) appears to be an essential part of succinate dehydrogenase. Finally a cytochrome c550 component with an apparent mid-point potential of Em = +195 mV has been detected.

  2. Deeply branching c6-like cytochromes of cyanobacteria.

    PubMed

    Bialek, Wojciech; Nelson, Matthew; Tamiola, Kamil; Kallas, Toivo; Szczepaniak, Andrzej

    2008-05-20

    The cyanobacterium Synechococcus sp. PCC 7002 carries two genes, petJ1 and petJ2, for proteins related to soluble, cytochrome c6 electron transfer proteins. PetJ1 was purified from the cyanobacterium, and both cytochromes were expressed with heme incorporation in Escherichia coli. The expressed PetJ1 displayed spectral and biochemical properties virtually identical to those of PetJ1 from Synechococcus. PetJ1 is a typical cytochrome c6 but contains an unusual KDGSKSL insertion. PetJ2 isolated from E. coli exhibited absorbance spectra characteristic of cytochromes, although the alpha, beta, and gamma bands were red-shifted relative to those of PetJ1. Moreover, the surface electrostatic properties and redox midpoint potential of PetJ2 (pI 9.7; E(m,7) = 148 +/- 1.7 mV) differed substantially from those of PetJ1 (pI 3.8; E(m,7) = 319 +/- 1.6 mV). These data indicate that the PetJ2 cytochrome could not effectively replace PetJ1 as an electron acceptor for the cytochrome bf complex in photosynthesis. Phylogenetic comparisons against plant, algal, bacterial, and cyanobacterial genomes revealed two novel and widely distributed clusters of previously uncharacterized, cyanobacterial c 6-like cytochromes. PetJ2 belongs to a group that is distinct from both c6 cytochromes and the enigmatic chloroplast c 6A cytochromes. We tentatively designate the PetJ2 group as c6C cytochromes and the other new group as c6B cytochromes. Possible functions of these cytochromes are discussed.

  3. Cerebral Folate Deficiency

    ERIC Educational Resources Information Center

    Gordon, Neil

    2009-01-01

    Cerebral folate deficiency (CFD) is associated with low levels of 5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) with normal folate levels in the plasma and red blood cells. The onset of symptoms caused by the deficiency of folates in the brain is at around 4 to 6 months of age. This is followed by delayed development, with deceleration…

  4. [Multiple cerebral tuberculomas].

    PubMed

    Noriega, L; Villarreal, F

    The tuberculosis is a disease that continues being important cause of morbidity and mortality at worldwide level. Its presentation as tuberculomas cerebral manifold at level of the central nervous system is little frequent in immunocompetent patients and can be confused with other etiology. An indigenous young man, immunocompetent consulted for history of headache, nausea, vomits, convulsions, double vision and hemiparesia left side, which in the cerebral tomography of revenue was showing injuries compatible with cerebral abscesses; for which he received treatment with antibiotics without improvement for what there takes biopsy of the injuries that reported tuberculomas, specific treatment being initiated later and the primary area being investigated without the same one be detecting. After the first procedural step with evident clinical and radiographic improvement. The tuberculosis in anyone of their forms of presentation must be included within the diagnosis differential of the patients in our endemic countries for this disease. The clinical and radiological diagnosis of cerebral injuries is difficult and single usually it obtains to the diagnosis during a pathology study that shows tuberculomas with caseosa necrosis, epiteliodes cell and the acid alcohol bacilli resistant.

  5. Cerebral Folate Deficiency

    ERIC Educational Resources Information Center

    Gordon, Neil

    2009-01-01

    Cerebral folate deficiency (CFD) is associated with low levels of 5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) with normal folate levels in the plasma and red blood cells. The onset of symptoms caused by the deficiency of folates in the brain is at around 4 to 6 months of age. This is followed by delayed development, with deceleration…

  6. Reversible cerebral vasoconstriction syndrome.

    PubMed

    Ducros, Anne

    2012-10-01

    Recurrent thunderclap headaches, seizures, strokes, and non-aneurysmal subarachnoid haemorrhage can all reveal reversible cerebral vasoconstriction syndrome. This increasingly recognised syndrome is characterised by severe headaches, with or without other symptoms, and segmental constriction of cerebral arteries that resolves within 3 months. Reversible cerebral vasoconstriction syndrome is supposedly due to a transient disturbance in the control of cerebrovascular tone. More than half the cases occur post partum or after exposure to adrenergic or serotonergic drugs. Manifestations have a uniphasic course, and vary from pure cephalalgic forms to rare catastrophic forms associated with several haemorrhagic and ischaemic strokes, brain oedema, and death. Diagnosis can be hampered by the dynamic nature of clinicoradiological features. Stroke can occur a few days after initial normal imaging, and cerebral vasoconstriction is at a maximum on angiograms 2-3 weeks after clinical onset. The calcium channel blocker nimodipine seems to reduce thunderclap headaches within 48 h of administration, but has no proven effect on haemorrhagic and ischaemic complications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. [Clinico-epidemiological characteristics of transient cerebral ischemia in the region of the Ukrainian Carpathian Mountains].

    PubMed

    Buletsa, B A; Lupich, P P; Litvinova, L A

    1991-01-01

    Altogether 225 patients with transitory derangements of cerebral circulation (TDCC) underwent clinico-laboratory examinations. Arterial hypertension and cerebral atherosclerosis turned out to be among most frequently occurring factors of TDCC. The provoking factors included psychoemotional stress and drops of barometric pressure. The course and outcome of TDCC were greatly affected by an increase in blood concentration of catecholamines and thyroid hormones. The high concentration of triiodothyronine in the blood contributed to the development of cerebral stroke.

  8. Stroke from Vasospasm due to Marijuana Use: Can Cannabis Synergistically with Other Medications Trigger Cerebral Vasospasm?

    PubMed

    Jamil, Marium; Zafar, Atif; Adeel Faizi, Syed; Zawar, Ifrah

    2016-01-01

    We present a case of imaging proven cerebral vasospasm causing ischemic stroke in a young patient chronically on buprenorphine-naloxone for heroin remission who started smoking cannabis on a daily basis. With cannabis legalization spreading across the states in the USA, it is important for physicians not only to be aware of cannabis reported association with cerebral vasospasm in some patients but also to be on the lookout for possible interacting medications that can synergistically affect cerebral vessels causing debilitating strokes.

  9. [Prothrombotic states and cerebral ischemia].

    PubMed

    Barinagarrementeria, F; González-Duarte, A; Cantú-Brito, C

    1998-01-01

    Hematological disorders per se represent unusual causes of cerebral ischemia, explaining in young people 4% of strokes. Hematological disorders that induce a thrombotic tendency contribute to overall ischemic stroke risk and may directly cause cerebral ischemia in patients without other risk factors. The frequency of cerebral infarctions caused by prothrombotic states is not known. This review will focus on disorders such as prothrombotic coagulopaties, including resistance to activated protein C and antiphospholipid syndrome as cause of cerebral infarction. Cerebral venous thrombosis and cerebral infarction from arterial origin are the most common form of neurological involvement. Pathophysiological mechanism of stroke in these patients are multiple and can include as in antiphospholipid syndrome embolism from valves abnormalities related to hematological disturbance, as well as thrombosis of extracranial or intracranial vessels. Is clear, however, that prothrombotic states could explains a high percentage of cases of those so called cryptogenic cerebral infarction in young people.

  10. Reduction of uranium by cytochrome c3 of Desulfovibrio vulgaris.

    PubMed Central

    Lovley, D R; Widman, P K; Woodward, J C; Phillips, E J

    1993-01-01

    The mechanism for U(VI) reduction by Desulfovibrio vulgaris (Hildenborough) was investigated. The H2-dependent U(VI) reductase activity in the soluble fraction of the cells was lost when the soluble fraction was passed over a cationic exchange column which extracted cytochrome c3. Addition of cytochrome c3 back to the soluble fraction that had been passed over the cationic exchange column restored the U(VI)-reducing capacity. Reduced cytochrome c3 was oxidized by U(VI), as was a c-type cytochrome(s) in whole-cell suspensions. When cytochrome c3 was combined with hydrogenase, its physiological electron donor, U(VI) was reduced in the presence of H2. Hydrogenase alone could not reduce U(VI). Rapid U(VI) reduction was followed by a subsequent slow precipitation of the U(IV) mineral uraninite. Cytochrome c3 reduced U(VI) in a uranium-contaminated surface water and groundwater. Cytochrome c3 provides the first enzyme model for the reduction and biomineralization of uranium in sedimentary environments. Furthermore, the finding that cytochrome c3 can catalyze the reductive precipitation of uranium may aid in the development of fixed-enzyme reactors and/or organisms with enhanced U(VI)-reducing capacity for the bioremediation of uranium-contaminated waters and waste streams. PMID:8285665

  11. Structure of the Schizosaccharomyces pombe cytochrome c gene

    SciTech Connect

    Russell, P.R.; Hall, B.D.

    1982-02-01

    The cytochrome c gene of the fission yeast Schizosaccharomyces pombe has been cloned by using the Saccharomyces cerevisiae iso-1-cytochrome c gene as a molecular hybridization probe. The DNA sequence and the 5' termini of the mRNA transcripts of the gene have been determined. The DNA sequence has confirmed, with two exceptions, the previously determined protein sequence. The nonrandom distribution of silent third base differences which was observed between the two cytochrome c genes of S. cerevisiae does not extend to the S. pombe cytochrome c gene, suggesting that there are no constraints other than protein function and codon usage which have acted to conserve the cytochrome c DNA sequences of the two yeasts. Introduction of the S. pombe cytochrome c gene on a yeast plasmid into a S. cerevisiae mutant which lacked functional cytochrome c transformed that recipient strain for the ability to grow on a nonfermentable carbon source. This implies that the S. pombe cytochrome c gene has all the regulatory signals which are required for its expression in S. cerevisiae, and that none of the amino acid differences between the cytochrome c proteins of the two yeasts has a drastic effect on the function of the protein in vivo.

  12. Reduction of uranium by cytochrome c3 of Desulfovibrio vulgaris

    USGS Publications Warehouse

    Lovley, D.R.; Widman, P.K.; Woodward, J.C.; Phillips, E.J.P.

    1993-01-01

    The mechanism for U(VI) reduction by Desulfovibrio vulgaris (Hildenborough) was investigated. The H2-dependent U(VI) reductase activity in the soluble fraction of the cells was lost when the soluble fraction was passed over a cationic exchange column which extracted cytochrome c3. Addition of cytochrome c3 back to the soluble fraction that had been passed over the cationic exchange column restored the U(VI)-reducing capacity. Reduced cytochrome c3 was oxidized by U(VI), as was a c-type cytochrome(s) in whole-cell suspensions. When cytochrome c3 was combined with hydrogenase, its physiological electron donor, U(VI) was reduced in the presence of H2. Hydrogenase alone could not reduce U(VI). Rapid U(VI) reduction was followed by a subsequent slow precipitation of the U(IV) mineral uraninite. Cytochrome c3 reduced U(VI) in a uranium-contaminated surface water and groundwater. Cytochrome c3 provides the first enzyme model for the reduction and biomineralization of uranium in sedimentary environments. Furthermore, the finding that cytochrome c3 can catalyze the reductive precipitation of uranium may aid in the development of fixed-enzyme reactors and/or organisms with enhanced U(VI)-reducing capacity for the bioremediation of uranium- contaminated waters and waste streams.

  13. Multi-heme cytochromes--new structures, new chemistry.

    PubMed

    Mowat, Christopher G; Chapman, Stephen K

    2005-11-07

    Heme is one of the most pervasive cofactors in nature and the c-type cytochromes represent one of the largest families of heme-containing proteins. Recent progress in bacterial genomic analysis has revealed a vast range of genes encoding novel c-type cytochromes that contain multiple numbers of heme cofactors. The genome sequence of Geobacter sulfurreducens, for example, includes some one hundred genes encoding c-type cytochromes, with around seventy of these containing two, or more, heme groups and with one protein containing an astonishing twenty seven heme groups. This wealth of cytochromes is of great significance in the respiratory flexibility shown by bacteria such as Geobacter. In addition, we are now discovering that many of these multi-heme cytochromes have associated enzymatic activities and in some cases this is revealing new chemistries. The purpose of this perspective is to describe recent progress in the structural and functional analyses of these new multi-heme cytochromes. To illustrate this we have chosen to focus on three of these cytochromes which exhibit catalytic activities; nitrite reductase, hydroxylamine oxidoreductase and tetrathionate reductase. In addition we consider the multi-heme cytochromes from Geobacter and Desulfovibrio species. Finally, we consider and contrast the repeating structural modules found in these multi-heme cytochromes.

  14. Cerebral Venous Thrombosis.

    PubMed

    Sassi, Samia Ben; Touati, Nahla; Baccouche, Hela; Drissi, Cyrine; Romdhane, Neila Ben; Hentati, Fayçal

    2016-01-01

    Data regarding cerebral venous thrombosis in North Africa are scarce. This study aims to identify the clinical features, risk factors, outcome, and prognosis of cerebral venous thrombosis in Tunisia. Data of 160 patients with radiologically confirmed cerebral venous thrombosis, hospitalized in Mongi Ben Hmida National Institute of Neurology (Tunis, Tunisia), were retrospectively collected and analyzed. The mean age was 37.3 years with a female predominance (83.1%). The mode of onset was subacute in most cases (56.2%). Headache was the most common symptom (71.3%), and focal neurologic symptoms were the main clinical presentation (41.8%). The most common sites of thrombosis were the superior sagittal sinus (65%) and the lateral sinus (60.6%). More than 1 sinus was involved in 114 (71.2%) patients. Parenchymal lesions observed in 85 (53.1%) patients did not correlate with cerebral venous thrombosis extent. Major risk factors were obstetric causes (pregnancy and puerperium) found in 46 (38.6% of women aged <50 years) patients, followed by anemia (28.1%) and congenital or acquired thrombophilia (16.2%). Mortality rate was of 6.6%. Good outcome at 6 months (modified Rankin Scale ≤2) was observed in 105 (87.5%)of 120 patients available for follow-up. Predictors of poor outcome were altered consciousness and elevated plasma C-reactive protein levels. Clinical and radiologic presentation of cerebral venous thrombosis in Tunisia was quite similar to other parts of the world with, however, a particularly high frequency of obstetric causes. Plasma C-reactive protein level should be considered as a prognostic factor in CVT.

  15. Evaluation of postural stability in children with hemiplegic cerebral palsy

    PubMed Central

    Kenis-Coskun, Ozge; Giray, Esra; Eren, Beyhan; Ozkok, Ozlem; Karadag-Saygi, Evrim

    2016-01-01

    [Purpose] Postural stability is the ability of to maintain the position of the body within the support area. This function is affected in cerebral palsy. The aim of the present study was to compare static and dynamic postural stability between children with hemiplegic cerebral palsy and healthy controls. [Subjects and Methods] Thirty-seven children between the ages of 5 and 14 diagnosed with hemiplegic cerebral palsy (19 right, 18 left) and 23 healthy gender- and age-matched controls were included in the study. Postural stability was evaluated in both of the groups using a Neurocom Balance. Sway velocity was measured both with the eyes open and closed. Sit to stand and turning abilities were also assessed. [Results] The sway velocities with the eyes open and closed were significantly different between the groups. The weight transfer time in the Sit to Stand test was also significantly slower in children with cerebral palsy. Children with cerebral palsy also showed slower turning times and greater sway velocities during the Step and Quick Turn test on a force plate compared with their healthy counterparts. [Conclusion] Both static and dynamic postural stability parameters are affected in hemiplegic cerebral palsy. Further research is needed to define rehabilitation interventions to improve these parameters in patients. PMID:27313338

  16. Role of Histamine and Its Receptors in Cerebral Ischemia

    PubMed Central

    2012-01-01

    Histamine is recognized as a neurotransmitter or neuromodulator in the brain, and it plays a major role in the pathogenic progression after cerebral ischemia. Extracellular histamine increases gradually after ischemia, and this may come from histaminergic neurons or mast cells. Histamine alleviates neuronal damage and infarct volume, and it promotes recovery of neurological function after ischemia; the H1, H2, and H3 receptors are all involved. Further studies suggest that histamine alleviates excitotoxicity, suppresses the release of glutamate and dopamine, and inhibits inflammation and glial scar formation. Histamine may also affect cerebral blood flow by targeting to vascular smooth muscle cells, and promote neurogenesis. Moreover, endogenous histamine is an essential mediator in the cerebral ischemic tolerance. Due to its multiple actions, affecting neurons, glia, vascular cells, and inflammatory cells, histamine is likely to be an important target in cerebral ischemia. But due to its low penetration of the blood-brain barrier and its wide actions in the periphery, histamine-related agents, like H3 antagonists and carnosine, show potential for cerebral ischemia therapy. However, important questions about the molecular aspects and pathophysiology of histamine and related agents in cerebral ischemia remain to be answered to form a solid scientific basis for therapeutic application. PMID:22860191

  17. Electrostatic analysis of the interaction of cytochrome c with native and dimethyl ester heme substituted cytochrome b5.

    PubMed

    Mauk, M R; Mauk, A G; Weber, P C; Matthew, J B

    1986-11-04

    The stability of the complex formed between cytochrome c and dimethyl ester heme substituted cytochrome b5 (DME-cytochrome b5) has been determined under a variety of experimental conditions to evaluate the role of the cytochrome b5 heme propionate groups in the interaction of the two native proteins. Interaction between cytochrome c and the modified cytochrome b5 was found to produce a difference spectrum in the visible range that is very similar to that generated by the interaction of the native proteins and that can be used to monitor complex formation between the two proteins. At pH 8 [25 degrees C (HEPPS), I = 5 mM], DME-cytochrome b5 and cytochrome c form a 1:1 complex with an association constant KA of 3 (1) X 10(6) M-1. This pH is the optimal pH for complex formation between these two proteins and is significantly higher than that observed for the interaction between the two native proteins. The stability of the complex formed between DME-cytochrome b5 and cytochrome c is strongly dependent on ionic strength with KA ranging from 2.4 X 10(7) M-1 at I = 1 mM to 8.2 X 10(4) M-1 at I = 13 mM [pH 8.0 (HEPPS), 25 degrees C]. Calculations for the native, trypsin-solubilized form of cytochrome b5 and cytochrome c confirm that the intermolecular complex proposed by Salemme [Salemme, F. R. (1976) J. Mol. Biol. 102, 563] describes the protein-protein orientation that is electrostatically favored at neutral pH.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Optical spectroscopy and prevention of deleterious cerebral vascular effects of ethanol by magnesium ions.

    PubMed

    Barbour, Randall L; Gebrewold, Asefa; Altura, Bella T; Altura, Burton M

    2002-06-28

    Previously, it has been suggested that acute ethanol (alcohol) administration can result in concentration-dependent vasoconstriction and decreased cerebral blood flow. Here, we present in vivo results using rapid (240 nm/min) optical backscatter measurements, with an intact cranial preparation in the rat, indicating that acute infusion of ethanol directly into the rat brain rapidly produces dose-dependent vasoconstriction of the cerebral microcirculation associated with a pronounced reduction in tissue blood content, pronounced rises in deoxyhemoglobin, significantly increased levels of reduced cytochrome oxidase and microvascular damage as the dose increases. Furthermore, we present in vivo experiments demonstrating the capability of magnesium ions (Mg(2+)) to attenuate and prevent these deleterious responses. Optical backscatter spectra (500-800 nm) were obtained by directing a single sending and receiving fiber to a portion of the left parietal cranium (in anesthetized rats), shaved to a translucent appearance to facilitate optical penetration. In the absence of added Mg(2+), infusion of a 10% solution of ethanol at 0.34 ml/min ( approximately 26.8 mg/min) produced prompt vasoconstriction as evidenced by a greater than 90% loss of oxyhemoglobin from the field-of-view and increases in levels of reduced cytochrome oxidase to between 50% and >90%. These effects were partially, to nearly completely, attenuated by the addition of MgCl(2) to the infusate containing added ethanol. Of special interest was the observation that attenuation of the vasoconstrictive effect of ethanol by Mg(2+) persisted despite a subsequent ethanol challenge without added Mg(2+). The results obtained demonstrate that, depending on dose, ethanol can produce prompt and severe vasoconstriction of the intact cerebral microcirculation and that infusion of moderate doses of Mg(2+) can largely attenuate and prevent this response. We conclude that appreciable, graded changes in cerebral cytochrome

  19. The axial ligands of heme in cytochromes: a near-infrared magnetic circular dichroism study of yeast cytochromes c, c1, and b and spinach cytochrome f.

    PubMed

    Simpkin, D; Palmer, G; Devlin, F J; McKenna, M C; Jensen, G M; Stephens, P J

    1989-10-03

    Room temperature near-infrared magnetic circular dichroism and low-temperature electron paramagnetic resonance measurements have been used to characterize the ligands of the heme iron in mitochondrial cytochromes c, c1, and b and in cytochrome f of the photosynthetic electron transport chain. The MCD data show that methionine is the sixth ligand of the heme of oxidized yeast cytochrome c1; the identify of this residue is inferred to be the single conserved methionine identified from a partial alignment of the available cytochrome c1 amino acid sequences. A different residue, which is most likely lysine, is the sixth heme ligand in oxidized spinach cytochrome f. The data for oxidized yeast cytochrome b are consistent with bis-histidine coordination of both hemes although the possibility that one of the hemes is ligated by histidine and lysine cannot be rigorously excluded. The neutral and alkaline forms of oxidized yeast cytochrome c have spectroscopic properties very similar to those of the horse heart proteins, and thus, by analogy, the sixth ligands are methionine and lysine, respectively.

  20. Cerebral hemodynamics during graded Valsalva maneuvers

    PubMed Central

    Perry, Blake G.; Cotter, James D.; Mejuto, Gaizka; Mündel, Toby; Lucas, Samuel J. E.

    2014-01-01

    The Valsalva maneuver (VM) produces large and abrupt changes in mean arterial pressure (MAP) that challenge cerebral blood flow and oxygenation. We examined the effect of VM intensity on middle cerebral artery blood velocity (MCAv) and cortical oxygenation responses during (phases I–III) and following (phase IV) a VM. Healthy participants (n = 20 mean ± SD: 27 ± 7 years) completed 30 and 90% of their maximal VM mouth pressure for 10 s (order randomized) whilst standing. Beat-to-beat MCAv, cerebral oxygenation (NIRS) and MAP across the different phases of the VM are reported as the difference from standing baseline. There were significant interaction (phase * intensity) effects for MCAv, total oxygenation index (TOI) and MAP (all P < 0.01). MCAv decreased during phases II and III (P < 0.01), with the greatest decrease during phase III (−5 ± 8 and −19 ± 15 cm·s−1 for 30 and 90% VM, respectively). This pattern was also evident in TOI (phase III: −1 ± 1 and −5 ± 4%, both P < 0.05). Phase IV increased MCAv (22 ± 15 and 34 ± 23 cm·s−1), MAP (15 ± 14 and 24 ± 17 mm Hg) and TOI (5 ± 6 and 7 ± 5%) relative to baseline (all P < 0.05). Cerebral autoregulation, indexed, as the %MCAv/%MAP ratio, showed a phase effect only (P < 0.001), with the least regulation during phase IV (2.4 ± 3.0 and 3.2 ± 2.9). These data illustrate that an intense VM profoundly affects cerebral hemodynamics, with a reactive hyperemia occurring during phase IV following modest ischemia during phases II and III. PMID:25309449

  1. Studies on cytochrome c oxidase activity of the cytochrome c1aa3 complex from Thermus thermophilus.

    PubMed

    Yoshida, T; Fee, J A

    1984-01-25

    Cytochrome oxidase from T. thermophilus is isolated as a noncovalent complex of cytochromes c1 and aa3 in which the four redox components of aa3 appear to be associated with a single approximately 55,000-D subunit while the heme C is associated with a approximately 33,000-D peptide (Yoshida, T., Lorence, R. M., Choc, M. G., Tarr, G. E., Findling, K. L., and Fee, J. A. (1983) J. Biol. Chem. 258, 112-123). We have examined the steady state transfer of electrons from ascorbate to oxygen by cytochrome c1aa3 as mediated by horse heart, Candida krusei, and T. thermophilus (c552) cytochromes c as well as tetramethylphenylenediamine (TMPD). These mediators exhibit simple Michaelis-Menten kinetic behavior yielding Vmax and KM values characteristic of the experimental conditions. Three classes of kinetic behavior were observed and are qualitatively discussed in terms of a reaction scheme. The data show that tetramethylphenyldiamine and cytochromes c react with the enzyme at independent sites; it is suggested that cytochrome c1 may efficiently transfer electrons to cytochrome aa3. When incorporated into phospholipid vesicles, the highly purified cytochrome c1aa3 was found to translocate one proton into the exterior medium for each molecule of cytochrome c552 oxidized. The combined results suggest that this bacterial enzyme functions in a manner generally identical with the more complex eucaryotic enzyme.

  2. Epilepsy, cerebral blood flow, and cerebral metabolic rate.

    PubMed

    Duncan, R

    1992-01-01

    Penfield's observations in the 1930s provided the first systematic evidence of changes in regional cerebral blood flow (rCBF) associated with focal seizures. Further studies in humans and animals confirmed increases in cerebral blood flow and metabolism during generalised seizures, but the interictal, ictal, and postictal changes in focal epilepsy have begun to be elucidated in the last decade with the advent of in vivo imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) and, in the case of animal studies, of autoradiography. Most studies have been of temporal lobe epilepsy. Interictally, the characteristic finding has been reduced blood flow and/or metabolism in the affected temporal lobe, or more extensively in the ipsilateral hemisphere. The few studies to date of ictal or postictal changes have been of rCBF using SPECT. They show hyperperfusion of the whole temporal lobe ictally, hyperperfusion of the hippocampus, combined with hypoperfusion of lateral structures in the immediate postictal period. Later in the postictal period, hypoperfusion alone is seen. Studies of focal seizures in animals have shown hyperperfusion and hypermetabolism at the site of the focus often with widespread depression of both parameters in the ipsilateral neocortex. Limited studies of coupling between blood flow and metabolism in humans have suggested that flow during seizures is adequate for metabolic demand, although some animal studies have suggested localised areas of uncoupling. The results of modern in vivo imaging of ictal and postictal changes in blood flow and metabolism have correlated well with Penfield's observations, and these changes are now being used to help localise epileptic foci, allowing wider use of the surgical treatment he pioneered.

  3. A role for cytochrome b5 in the In vivo disposition of anticancer and cytochrome P450 probe drugs in mice.

    PubMed

    Henderson, Colin J; McLaughlin, Lesley A; Finn, Robert D; Ronseaux, Sebastien; Kapelyukh, Yury; Wolf, C Roland

    2014-01-01

    The role of microsomal cytochrome b5 (Cyb5) in defining the rate of drug metabolism and disposition has been intensely debated for several decades. Recently we described mouse models involving the hepatic or global deletion of Cyb5, demonstrating its central role in in vivo drug disposition. We have now used the cytochrome b5 complete null (BCN) model to determine the role of Cyb5 in the metabolism of ten pharmaceuticals metabolized by a range of cytochrome P450s, including five anticancer drugs, in vivo and in vitro. The extent to which metabolism was significantly affected by the absence of Cyb5 was substrate-dependent; AUC increased (75-245%) and clearance decreased (35-72%) for phenacetin, metoprolol, and chlorzoxazone. Tolbutamide disposition was not significantly altered by Cyb5 deletion, while for midazolam clearance was decreased by 66%. The absence of Cyb5 had no effect on gefitinib and paclitaxel disposition, while significant changes in the in vivo pharmacokinetics were measured for: cyclophosphamide [maximum plasma concentration (Cmax) and terminal half-life increased 55% and 40%, respectively], tamoxifen (AUClast and Cmax increased 370% and 233%, respectively), and anastrozole (AUC and terminal half-life increased 125% and 62%, respectively; clearance down 80%). These data provide strong evidence that both hepatic and extrahepatic Cyb5 levels are an important determinant of in vivo drug disposition catalyzed by a range of cytochrome P450s, including currently prescribed anticancer agents, and that individuality in Cyb5 expression could be a significant determinant in rates of drug disposition in man.

  4. A role for cytochrome b5 in the in vivo disposition of anti-cancer and cytochrome P450 probe drugs in mice

    PubMed Central

    Henderson, Colin J.; McLaughlin, Lesley A.; Finn, Robert D.; Ronseaux, Sebastien; Kapelyukh, Yury; Wolf, C. Roland

    2014-01-01

    The role of microsomal cytochrome b5 (Cyb5) in defining the rate of drug metabolism and disposition has been intensely debated for several decades. Recently we described mouse models involving the hepatic or global deletion of Cyb5, demonstrating its central role in in vivo drug disposition. We have now used the cytochrome b5 complete null (BCN) model to determine the role of Cyb5 in the metabolism of ten pharmaceuticals metabolised by a range of cytochrome P450s, including five anti-cancer drugs, in vivo and in vitro. The extent to which metabolism was significantly affected by the absence of Cyb5 was substrate-dependent, with AUC increased (75-245%), and clearance decreased (35-72%), for phenacetin, metoprolol and chlorzoxazone. Tolbutamide disposition was not significantly altered by Cyb5 deletion, while for midazolam clearance was decreased by 66%. The absence of Cyb5 had no effect on gefitinib and paclitaxel disposition, while significant changes in the in vivo pharmacokinetics of cyclophosphamide were measured (Cmax and terminal half-life increased 55% and 40%, respectively), tamoxifen (AUClast and Cmax increased 370% and 233%, respectively) and anastrozole (AUC and terminal half-life increased 125% and 62%, respectively; clearance down 80%). These data from provide strong evidence that both hepatic and extra-hepatic Cyb5 levels are an important determinant of in vivo drug disposition catalysed by a range of cytochrome P450s, including currently-prescribed anti-cancer agents, and that individuality in Cyb5 expression could be a significant determinant in rates of drug disposition in man. PMID:24115751

  5. Biochemical and biophysical properties of cytochrome o of Azotobacter vinelandii.

    PubMed

    Yang, T

    1986-03-12

    Cytochrome o, solubilized from the membrane of Azotobacter vinelandii, has been purified to homogeneity as judged by ultracentrifugation and polyacrylamide gel electrophoresis. The detergent-containing cytochrome o is composed of one polypeptide chain with a molecular weight of 28 000-29 000, associated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The enzyme exists as a dimer by gel filtration analysis. The amino analysis which reveals the majority of residues are of hydrophobic nature. The cytochrome o oxidase contains protoheme as its prosthetic group and about 20-40% of phospholipids. The phospholipids are identified as phosphatidylethanolamine and phosphatidylglycerol by radioautographic analysis using 2-dimensional thin-layer chromatography. No copper or nonheme iron can be detected in the purified oxidase preparation by atomic absorption and chemical analyses. Oxidation-reduction titration shows this membrane-bound cytochrome o to be a low-potential component, and Em was determined to be -18 mV in the purified form and -30 mV in the membrane-bound form. Both forms bind CO with a reduced absorption peak at 559 and 557-558 nm in the native and solubilized forms, respectively. A high-spin (g = 6.0) form is assigned to the oxidized cytochrome o by electron paramagnetic resonance analysis, and KCN abolishes this high-spin signal. CO titration of purified cytochrome o in the anaerobic conditions shows the enzyme binds one CO per four protohemes and a dissociation constant is estimated to be 3.2 microM for CO. Cyanide reacts with purified cytochrome o in both oxidized and CO-bound forms, identified by specific spectral compounds absorbed at the Soret region. Cytochrome c, often co-purified with cytochrome c from the membrane, cannot serve as a reductant for cytochrome o in vitro, due to the apparent potential difference of about 300 mV. Upon separation, both cytochrome o and cytochrome c4 show a great tendency of aggregation

  6. Production of recombinant multiheme cytochromes c in Wolinella succinogenes.

    PubMed

    Kern, Melanie; Simon, Jörg

    2011-01-01

    Respiratory nitrogen cycle processes like nitrification, nitrate reduction, denitrification, nitrite ammonification, or anammox involve a variety of dissimilatory enzymes and redox-active cofactors. In this context, an intriguing protein class are cytochromes c, that is, enzymes containing one or more covalently bound heme groups that are attached to heme c binding motifs (HBMs) of apo-cytochromes. The key enzyme of the corresponding maturation process is cytochrome c heme lyase (CCHL), an enzyme that catalyzes the formation of two thioether linkages between two vinyl side chains of a heme and two cysteine residues arranged in the HBM. In recent years, many multiheme cytochromes c involved in nitrogen cycle processes, such as hydroxylamine oxidoreductase and cytochrome c nitrite reductase, have attracted particular interest. Structurally, these enzymes exhibit conserved heme packing motifs despite displaying very different enzymic properties and largely unrelated primary structures. The functional and structural characterization of cytochromes c demands their purification in sufficient amounts as well as the feasibility to generate site-directed enzyme variants. For many interesting organisms, however, such systems are not available, mainly hampered by genetic inaccessibility, slow growth rates, insufficient cell yields, and/or a low capacity of cytochrome c formation. Efficient heterologous cytochrome c overproduction systems have been established using the unrelated proteobacterial species Escherichia coli and Wolinella succinogenes. In contrast to E. coli, W. succinogenes uses the cytochrome c biogenesis system II and contains a unique set of three specific CCHL isoenzymes that belong to the unusual CcsBA-type. Here, W. succinogenes is presented as host for cytochrome c overproduction focusing on a recently established gene expression system designed for large-scale production of multiheme cytochromes c. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Changes in regional cerebral blood flow in the right cortex homologous to left language areas are directly affected by left hemispheric damage in aphasic stroke patients: evaluation by Tc-ECD SPECT and novel analytic software.

    PubMed

    Uruma, G; Kakuda, W; Abo, M

    2010-03-01

    The objective of this study was to clarify the influence of regional cerebral blood flow (rCBF) changes in language-relevant areas of the dominant hemisphere on rCBF in each region in the non-dominant hemisphere in post-stroke aphasic patients. The study subjects were 27 aphasic patients who suffered their first symptomatic stroke in the left hemisphere. In each subject, we measured rCBF by means of 99mTc-ethylcysteinate dimmer single photon emission computed tomography (SPECT). The SPECT images were analyzed by the statistical imaging analysis programs easy Z-score Imaging System (eZIS) and voxel-based stereotactic extraction estimation (vbSEE). Segmented into Brodmann Area (BA) levels, Regions of Interest (ROIs) were set in language-relevant areas bilaterally, and changes in the relative rCBF as average negative and positive Z-values were computed fully automatically. To assess the relationship between rCBF changes of each ROIs in the left and right hemispheres, the Spearman ranked correlation analysis and stepwise multiple regression analysis were applied. Globally, a negative and asymmetric influence of rCBF changes in the language-relevant areas of the dominant hemisphere on the right hemisphere was found. The rCBF decrease in left BA22 significantly influenced the rCBF increase in right BA39, BA40, BA44 and BA45. The results suggested that the chronic increase in rCBF in the right language-relevant areas is due at least in part to reduction in the trancallosal inhibitory activity of the language-dominant left hemisphere caused by the stroke lesion itself and that these relationships are not always symmetric.

  8. Noninvasive measurement of cerebral oxygen saturation and cerebral phronetal function

    NASA Astrophysics Data System (ADS)

    Li, Shengli; Zhang, Aiyu; Xu, Min; Jin, Taiyi

    1998-08-01

    Using the Near-Infrared Spectroscopy (NIRS), the noninvasive measurement of cerebral oxygen concentration can be achieved in vivo based on the Lambert-Beer Law. In this paper, we discuss the possibility of studying higher brain functions through combining cerebral oxygen saturation and cerebral function measurement. Event-related experiments are introduced to measure the cerebral phronetal function. Time domain curves show sight differences among these experiment results. However, with the aid of DFT, experiment data of all five human volunteers show the frequency near 20 Hz or 40 Hz is evoked depending on the difficulty of the mental tasks. The results demonstrate the feasibility of cerebral functions study by means of cerebral oxygen saturation measurement analyzed in the frequency domain.

  9. Cytochrome P450-2D6 Screening Among Elderly Using Antidepressants (CYSCE)

    ClinicalTrials.gov

    2017-08-15

    Depression; Depressive Disorder; Poor Metabolizer Due to Cytochrome P450 CYP2D6 Variant; Intermediate Metabolizer Due to Cytochrome P450 CYP2D6 Variant; Ultrarapid Metabolizer Due to Cytochrome P450 CYP2D6 Variant

  10. Contribution of cytochrome P-450 omega-hydroxylase to altered arteriolar reactivity with high-salt diet and hypertension.

    PubMed

    Frisbee, J C; Falck, J R; Lombard, J H

    2000-05-01

    The present study evaluated the contribution of cytochrome P-450 omega-hydroxylase in modulating the reactivity of cremaster muscle arterioles in normotensive rats on high-salt (HS) and low-salt (LS) diet and in rats with reduced renal mass hypertension (RRM-HT). Changes in arteriolar diameter in response to ACh, sodium nitroprusside (SNP), ANG II, and elevated O(2) were measured via television microscopy under control conditions and following cytochrome P-450 omega-hydroxylase inhibition with 17-octadecynoic acid (17-ODYA) or N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS). In normotensive rats on either LS or HS diet, resting tone was unaffected and arteriolar reactivity to ACh or SNP was minimally affected by cytochrome P-450 omega-hydroxylase inhibition. In RRM-HT rats, cytochrome P-450 omega-hydroxylase inhibition reduced resting tone and significantly enhanced arteriolar dilation to ACh and SNP. Treatment with 17-ODYA or DDMS inhibited arteriolar constriction to ANG II and O(2) in all the groups, although the degree of inhibition was greater in RRM-HT than in normotensive animals. These results suggest that metabolites of cytochrome P-450 omega-hydroxylase contribute to the altered reactivity of skeletal muscle arterioles to vasoconstrictor and vasodilator stimuli in RRM-HT.

  11. The bacterial SoxAX cytochromes.

    PubMed

    Kappler, Ulrike; Maher, Megan J

    2013-03-01

    SoxAX cytochromes are heme-thiolate proteins that play a key role in bacterial thiosulfate oxidation, where they initiate the reaction cycle of a multi-enzyme complex by catalyzing the attachment of sulfur substrates such as thiosulfate to a conserved cysteine present in a carrier protein. SoxAX proteins have a wide phylogenetic distribution and form a family with at least three distinct types of SoxAX protein. The types of SoxAX cytochromes differ in terms of the number of heme groups present in the proteins (there are diheme and triheme versions) as well as in their subunit structure. While two of the SoxAX protein types are heterodimers, the third group contains an additional subunit, SoxK, that stabilizes the complex of the SoxA and SoxX proteins. Crystal structures are available for representatives of the two heterodimeric SoxAX protein types and both of these have shown that the cysteine ligand to the SoxA active site heme carries a modification to a cysteine persulfide that implicates this ligand in catalysis. EPR studies of SoxAX proteins have also revealed a high complexity of heme dependent signals associated with this active site heme; however, the exact mechanism of catalysis is still unclear at present, as is the exact number and types of redox centres involved in the reaction.

  12. Identification of two new cytochrome P450 genes and RNA interference to evaluate their roles in detoxification of commonly used insecticides in Locusta migratoria.

    PubMed

    Guo, Yanqiong; Zhang, Jianzhen; Yu, Rongrong; Zhu, Kun Yan; Guo, Yaping; Ma, Enbo

    2012-05-01

    Cytochrome P450 monooxygenases (cytochrome P450s), found in virtually all living organisms, play an important role in the metabolism of xenobiotics such as drugs, pesticides, and plant toxins. We have previously evaluated the responses of the oriental migratory locust (Locusta migratoria) to the pyrethroid insecticide deltamethrin and revealed that increased cytochrome P450 enzyme activity was due to increased transcription of multiple cytochrome P450 genes. In this study, we identified for the first time two new cytochrome P450 genes, which belong to two novel cytochrome P450 gene families. CYP409A1 belongs to CYP409 family whereas CYP408B1 belongs to CYP408 family. Our molecular analysis indicated that CYP409A1 was mainly expressed in fatbodies, midgut, gastric caecum, foregut and Malpighian tubules of the third- and fourth-instar nymphs, whereas CYP408B1 was mainly expressed in foregut, hindgut and muscle of the insects at all developmental stages examined. The expression of these two cytochrome P450 genes were differentially affected by three representative insecticides, including carbaryl (carbamate), malathion (organophosphate) and deltamethrin (pyrethroid). The exposure of the locust to carbaryl, malathion and deltamethrin resulted in reduced, moderately increased and significantly increased transcript levels, respectively, of the two cytochrome P450 genes. Our further analysis of their detoxification roles by using RNA interference followed by deltamethrin bioassay showed increased nymph mortalities by 21.1% and 16.7%, respectively, after CYP409A1 and CYP408B1 were silenced. These results strongly support our notion that these two new cytochrome P450 genes play an important role in deltamethrin detoxification in the locust.

  13. PUMA is invovled in ischemia/reperfusion-induced apoptosis of mouse cerebral astrocytes.

    PubMed

    Chen, H; Tian, M; Jin, L; Jia, H; Jin, Y

    2015-01-22

    PUMA (p53-upregulated modulator of apoptosis), a BH3-only member of the Bcl-2 protein family, is required for p53-dependent and p53-independent forms of apoptosis. PUMA has been invovled in the onset and progress of several diseases, including cancer, acquired immunodeficiency syndrome, and ischemic brain disease. Although many studies have shown that ischemia and reperfusion (I/R) can induce the apoptosis of astrocytes, the role of PUMA in I/R-mediated apoptosis of cerebral astrocyte apoptosis remains unclear. To mimic in vivo I/R conditions, primary mouse cerebral astrocytes were incubated in a combinational cultural condition of oxygen, glucose, and serum deprivation (OSGD) for 1 h followed by reperfusion (OSGD/R). Cell death determination assays and cell viability assays indicated that OSGD and OSGD/R induce the apoptosis of primary cerebral astrocytes. The expression of PUMA was significantly elevated in primary cerebral astrocytes during OSGD/R. Moreover, targeted down-regulation of PUMA by siRNA transfection significantly decreased the OSGD/R-induced apoptosis of primary cerebral astrocytes. We also found that OSGD and OSGD/R triggered the release of cytochrome c in astrocytes, indicating the dependence on a mitochondrial apoptotic pathway. Reactive oxygen species (ROS) was extremely generated during OSGD and OSGD/R, and the elimination of ROS by treated with N-acetyl-L-cysteine (NAC) remarkably inhibited the expression of PUMA and the apoptosis of primary cerebral astrocytes. The activation of Caspase 3 and Caspase 9 was extremely elevated in primary cerebral astrocytes during OSGD. In addition, we found that knockdown of PUMA led to the depressed expression of Bax, cleaved caspase-9 and caspase-3 during OSGD/R. These results indicate that PUMA is invovled in the apoptosis of cerebral astrocytes upon I/R injury.

  14. Influence of acetyl-carnitine on some mitochondrial enzymic activities in the human cerebral tissue in conditions of acute hypoxia.

    PubMed

    Corbucci, G G; Melis, A; Piga, M; Marchionni, A; Calvani, M

    1992-01-01

    Following previous research on human tissue in conditions of acute and massive hypoxia, in the present work the authors compared the cellular enzymic response to oxidative stress in normoxic (perifocal) and hypoxic (focal) areas in human brain affected by regional acute vasculopathies. Two homogeneous groups of patients were selected following strict clinical inclusion/exclusion criteria. The groups of patients were treated with a placebo or acetyl-carnitine at same doses and following randomized, double-blind procedures. The focal areas showed a significant functional damage in lactate, pyruvate and succinate dehydrogenases and in the cytochrome oxidase activity when compared with the enzymic capacities of perifocal areas (normoxic as controls). The pretreatment with acetyl-carnitine antagonized the above-mentioned enzymic damage by a protective action linked to the endocellular energy restoration. In accordance with these data, the therapeutic role played by acetyl-carnitine in the cerebral focal hypoxia appeared to be a determinant for the cell survival mainly in the reversible phase of oxidative damage.

  15. Cerebral malaria--clinical manifestations and pathogenesis.

    PubMed

    Hora, Rachna; Kapoor, Payal; Thind, Kirandeep Kaur; Mishra, Prakash Chandra

    2016-04-01

    One of the most common central nervous system diseases in tropical countries is cerebral malaria (CM). Malaria is a common protozoan infection that is responsible for enormous worldwide mortality and economic burden on the society. Episodes of Plasmodium falciparum (Pf) caused CM may be lethal, while survivors are likely to suffer from persistent debilitating neurological deficits, especially common in children. In this review article, we have summarized the various symptoms and manifestations of CM in children and adults, and entailed the molecular basis of the disease. We have also emphasized how pathogenesis of the disease is effected by the parasite and host responses including blood brain barrier (BBB) disruption, endothelial cell activation and apoptosis, nitric oxide bioavailability, platelet activation and apoptosis, and neuroinflammation. Based on a few recent studies carried out in experimental mouse malaria models, we propose a basis for the neurological deficits and sequelae observed in human cerebral malaria, and summarize how existing drugs may improve prognosis in affected individuals.

  16. Managing Malignant Cerebral Infarction

    PubMed Central

    Sahuquillo, Juan; Sheth, Kevin N.; Kahle, Kristopher T.; Walcott, Brian P.

    2011-01-01

    Opinion statement Managing patients with malignant cerebral infarction remains one of the foremost challenges in medicine. These patients are at high risk for progressive neurologic deterioration and death due to malignant cerebral edema, and they are best cared for in the intensive care unit of a comprehensive stroke center. Careful initial assessment of neurologic function and of findings on MRI, coupled with frequent reassessment of clinical and radiologic findings using CT or MRI are mandatory to promote the prompt initiation of treatments that will ensure the best outcome in these patients. Significant deterioration in either neurologic function or radiologic findings or both demand timely treatment using the best medical management, which may include osmotherapy (mannitol or hypertonic saline), endotracheal intubation, and mechanical ventilation. Under appropriate circumstances, decompressive craniectomy may be warranted to improve outcome or to prevent death. PMID:21190097

  17. Intensive Dysarthria Therapy for Older Children with Cerebral Palsy: Findings from Six Cases

    ERIC Educational Resources Information Center

    Pennington, Lindsay; Smallman, Claire; Farrier, Faith

    2006-01-01

    Children with cerebral palsy often have speech, language and communication difficulties that affect their access to social and educational activities. Speech and language therapy to improve the intelligibility of the speech of children with cerebral palsy has long been advocated, but there is a dearth of research investigating therapy…

  18. Fever of unexplained origin, biochemical Cushing's disease and cerebral dysrhythmia corrected by valproate sodium.

    PubMed

    López-Moreno, J M; Rodríguez-Portales, J A; Mahana, D

    1985-01-15

    A patient with cerebral dysrhythmia and fever of unexplained origin for 2 years is described. She had elevated and nonsuppressible levels of urinary 17-hydroxycorticosteroids but no clinical features of hypercortisolism. Treatment with valproate sodium corrected all the abnormalities. It is postulated that cerebral dysrhythmia can affect the hypothalamic mechanisms of body temperature and regulation of adrenocorticotropic hormone levels.

  19. Intensive Dysarthria Therapy for Older Children with Cerebral Palsy: Findings from Six Cases

    ERIC Educational Resources Information Center

    Pennington, Lindsay; Smallman, Claire; Farrier, Faith

    2006-01-01

    Children with cerebral palsy often have speech, language and communication difficulties that affect their access to social and educational activities. Speech and language therapy to improve the intelligibility of the speech of children with cerebral palsy has long been advocated, but there is a dearth of research investigating therapy…

  20. c-Type Cytochrome Assembly Is a Key Target of Copper Toxicity within the Bacterial Periplasm

    PubMed Central

    Durand, Anne; Azzouzi, Asma; Bourbon, Marie-Line; Steunou, Anne-Soisig; Liotenberg, Sylviane; Maeshima, Akinori; Astier, Chantal; Argentini, Manuela; Saito, Shingo

    2015-01-01

    ABSTRACT In the absence of a tight control of copper entrance into cells, bacteria have evolved different systems to control copper concentration within the cytoplasm and the periplasm. Central to these systems, the Cu+ ATPase CopA plays a major role in copper tolerance and translocates copper from the cytoplasm to the periplasm. The fate of copper in the periplasm varies among species. Copper can be sequestered, oxidized, or released outside the cells. Here we describe the identification of CopI, a periplasmic protein present in many proteobacteria, and show its requirement for copper tolerance in Rubrivivax gelatinosus. The ΔcopI mutant is more susceptible to copper than the Cu+ ATPase copA mutant. CopI is induced by copper, localized in the periplasm and could bind copper. Interestingly, copper affects cytochrome c membrane complexes (cbb3 oxidase and photosystem) in both ΔcopI and copA-null mutants, but the causes are different. In the copA mutant, heme and chlorophyll synthesis are affected, whereas in ΔcopI mutant, the decrease is a consequence of impaired cytochrome c assembly. This impact on c-type cytochromes would contribute also to the copper toxicity in the periplasm of the wild-type cells when they are exposed to high copper concentrations. PMID:26396241

  1. The photosynthetic cytochrome c 550 from the diatom Phaeodactylum tricornutum.

    PubMed

    Bernal-Bayard, Pilar; Puerto-Galán, Leonor; Yruela, Inmaculada; García-Rubio, Inés; Castell, Carmen; Ortega, José M; Alonso, Pablo J; Roncel, Mercedes; Martínez, Jesús I; Hervás, Manuel; Navarro, José A

    2016-12-28

    The photosynthetic cytochrome c 550 from the marine diatom Phaeodactylum tricornutum has been purified and characterized. Cytochrome c 550 is mostly obtained from the soluble cell extract in relatively large amounts. In addition, the protein appeared to be truncated in the last hydrophobic residues of the C-terminus, both in the soluble cytochrome c 550 and in the protein extracted from the membrane fraction, as deduced by mass spectrometry analysis and the comparison with the gene sequence. Interestingly, it has been described that the C-terminus of cytochrome c 550 forms a hydrophobic finger involved in the interaction with photosystem II in cyanobacteria. Cytochrome c 550 was almost absent in solubilized photosystem II complex samples, in contrast with the PsbO and Psb31 extrinsic subunits, thus suggesting a lower affinity of cytochrome c 550 for the photosystem II complex. Under iron-limiting conditions the amount of cytochrome c 550 decreases up to about 45% as compared to iron-replete cells, pointing to an iron-regulated synthesis. Oxidized cytochrome c 550 has been characterized using continuous wave EPR and pulse techniques, including HYSCORE, and the obtained results have been interpreted in terms of the electrostatic charge distribution in the surroundings of the heme centre.

  2. Periplasmic c cytochromes and chlorate reduction in Ideonella dechloratans.

    PubMed

    Bäcklund, Anna Smedja; Bohlin, Jan; Gustavsson, Niklas; Nilsson, Thomas

    2009-04-01

    The aim of this study was to clarify the pathway of electron transfer between the inner membrane components and the periplasmic chlorate reductase. Several soluble c-type cytochromes were found in the periplasm. The optical difference spectrum of dithionite-reduced periplasmic extract shows that at least one of these components is capable of acting as an electron donor to the enzyme chlorate reductase. The cytochromes were partially separated, and the fractions were analyzed by UV/visible spectroscopy to determine the ability of donating electrons to chlorate reductase. Our results show that one of the c cytochromes (6 kDa) is able to donate electrons, both to chlorate reductase and to the membrane-bound cytochrome c oxidase, whereas the roles of the remaining c cytochromes still remain to be elucidated. Peptide extracts of the c cytochromes were obtained by tryptic in-gel digestion for matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis. Peptide sequences obtained indicate that the 6-kDa cytochrome c protein is similar to c cytochromes from the chlorate-reducing bacterium Dechloromonas aromatica.

  3. Modeling Cerebral Vascular Injury

    DTIC Science & Technology

    2016-01-01

    Using a pressure gradient to drive the blood flow, and the external pressure induced by a blast wave through the surrounding brain elements, an...unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Many numerical models for the brain do not include the vascular structures within the brain and thus...are incapable of predicting damage to the cerebral vasculature. The presence of the vasculature within the brain produces a reinforcing effect and

  4. 10-(6'-Plastoquinonyl)decyltriphenylphosphonium (SkQ1) Does Not Increase the Level of Cytochromes P450 in Rat Liver and Human Hepatocyte Cell Culture.

    PubMed

    Myasoedova, K N; Silachev, D N; Petrov, A D

    2016-12-01

    Mitochondria-targeted antioxidant SkQ1 did not increase the content of cytochromes P450 in livers of rats that were given SkQ1 in drinking water for 5 days in a dose (2.5 µmol per kg body weight) that exceeded 10 times the SkQ1 therapeutic dose. SkQ1 did not affect the levels of cytochrome P450 forms CYP1A2, CYP2B6, and CYP3A4 in monolayer cultures of freshly isolated human hepatocytes, while specific inducers of these forms (omeprazole, phenobarbital, and rifampicin, respectively) significantly increased expression of the cytochromes P450 under the same conditions. We conclude that therapeutic doses of SkQ1 do not induce cytochromes P450 in liver, and the absence of the inducing effect cannot be explained by poor availability of hepatocytes to SkQ1 in vivo.

  5. Primary cerebral malignant melanoma

    PubMed Central

    Tang, Kai; Kong, Xiangyi; Mao, Gengsheng; Qiu, Ming; Zhu, Haibo; Zhou, Lei; Nie, Qingbin; Xu, Yi; Du, Shiwei

    2017-01-01

    Abstract Primary intracranial melanomas are uncommon and constitute approximately 1% of all melanoma cases and 0.07% of all brain tumors. In nature, these primary melanomas are very aggressive and can spread to other organs. We report an uncommon case of primary cerebral malignant melanoma—a challenging diagnosis guided by clinical presentations, radiological features, and surgical biopsy results, aiming to emphasize the importance of considering primary melanoma when making differential diagnoses of intracranial lesions. We present a rare case of a primary cerebral melanoma in the left temporal lobe. The mass appeared iso-hypodense on brain computed tomography (CT), short signal on T1-weighted magnetic resonance images (T1WI) and long signal on T2WI. It was not easy to make an accurate diagnosis before surgery. We showed the patient's disease course and reviewed related literatures, for readers’ reference. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary. After surgery, the pathological examination confirmed the diagnosis of melanoma. The patient was discharged without any complications and went on to receive adjuvant radiochemotherapy. It is difficult to diagnose primary cerebral melanoma in the absence of any cutaneous melanosis. A high index of clinical suspicion along with good pathology reporting is the key in diagnosing these extremely rare tumors. PMID:28121927

  6. Cerebral oxygenation and hyperthermia

    PubMed Central

    Bain, Anthony R.; Morrison, Shawnda A.; Ainslie, Philip N.

    2014-01-01

    Hyperthermia is associated with marked reductions in cerebral blood flow (CBF). Increased distribution of cardiac output to the periphery, increases in alveolar ventilation and resultant hypocapnia each contribute to the fall in CBF during passive hyperthermia; however, their relative contribution remains a point of contention, and probably depends on the experimental condition (e.g., posture and degree of hyperthermia). The hyperthermia-induced hyperventilatory response reduces arterial CO2 pressure (PaCO2) causing cerebral vasoconstriction and subsequent reductions in flow. During supine passive hyperthermia, the majority of recent data indicate that reductions in PaCO2 may be the primary, if not sole, culprit for reduced CBF. On the other hand, during more dynamic conditions (e.g., hemorrhage or orthostatic challenges), an inability to appropriately decrease peripheral vascular conductance presents a condition whereby adequate cerebral perfusion pressure may be compromised secondary to reductions in systemic blood pressure. Although studies have reported maintenance of pre-frontal cortex oxygenation (assessed by near-infrared spectroscopy) during exercise and severe heat stress, the influence of cutaneous blood flow is known to contaminate this measure. This review discusses the governing mechanisms associated with changes in CBF and oxygenation during moderate to severe (i.e., 1.0°C to 2.0°C increase in body core temperature) levels of hyperthermia. Future research directions are provided. PMID:24624095

  7. Reversible cerebral vasoconstriction syndrome.

    PubMed

    Sampaio Rocha Filho, Pedro Augusto; Santos Barbosa, Janayna; Melo Correa-Lima, Ana Rosa

    2010-08-01

    Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache associated with multifocal vasoconstriction of cerebral arteries in patients without aneurysmal subarachnoid hemorrhage (SAH). The vasoconstriction reverts within three months. We report a 44-year-old man who had a thunderclap headache during sexual intercourse. A similar episode occurred at rest 36 hours later. The patient had already experienced a thunderclap headache 10 years earlier, during coitus. There were no abnormalities on examination. His brain computed tomography scan was normal and cerebrospinal fluid analysis showed no xanthochromia, 15 WBC/mm³ and 10 RBC/mm³. Lumbar puncture was repeated two days later (WBC = 3/mm³ and RBC = 43/mm³). An initial digital cerebral angiography showed a diffuse segmental intracerebral vasospasm. A new angiography after 15 days was normal. He remains headache-free after twenty six months. In conclusion, patients who have thunderclap headache with normal brain CT and cerebrospinal fluid without xantochromia should be investigated for this syndrome.

  8. Sublocalization of Cytochrome b6f Complexes in Photosynthetic Membranes.

    PubMed

    Kirchhoff, Helmut; Li, Meng; Puthiyaveetil, Sujith

    2017-07-01

    It is well established that the majority of energy-converting photosynthetic protein complexes in plant thylakoid membrane are nonhomogenously distributed between stacked and unstacked membrane regions. Yet, the sublocalization of the central cytochrome b6f complex remains controversial. We present a structural model that explains the variation in cytochrome b6f sublocalization data. Small changes in the distance between adjacent membranes in stacked grana regions either allow or restrict access of cytochrome b6f complexes to grana. If the width of the gap falls below a certain threshold, then the steric hindrance prevents cytochrome b6f access to grana. Evidence is presented that the width of stromal gap is variable, demonstrating that the postulated mechanism can regulate the lateral distribution of the cytochrome b6f complexes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Midpoint potentials of the mitochondrial cytochromes of Crithidia fasciculata.

    PubMed Central

    Kusel, J P; Storey, B T

    1976-01-01

    The midpoint potentials of the mitochondrial respiratory chain cytochromes of the protozoan Crithidia fasciculata at pH 7.2, Em7.2, show great similarity to those measured in higher organisms. Values of Em7.2 for cytochromes a and a3 are +165 and +340 mV. Both c cytochromes have Em7.2 = +230 mV. There are two b cytochromes with the same spectral characteristics with Em7.2 = -20 and -135 mV. These values are compatible with two sites of energy conservation for oxidative phosphorylation in these mitochondria. All cytochrome components show potentiometric titrations with n = 1. There is a fluorescent flavoprotein in these mitochondria with Em7.2 = -40 mV and n =2, whose function is not known. PMID:986389

  10. Cytochrome P-450 from the Mesocarp of Avocado (Persea americana)

    PubMed Central

    O'Keefe, Daniel P.; Leto, Kenneth J.

    1989-01-01

    The microsomal fraction from the mesocarp of avocado (Persea americana) is one of few identified rich sources of plant cytochrome P-450. Cytochrome P-450 from this tissue has been solubilized and purified. Enzymatic assays (p-chloro-N-methylaniline demethylase) and spectroscopic observations of substrate binding suggest a low spin form of the cytochrome, resembling that in the microsomal membrane, can be recovered. However, this preparation of native protein is a mixture of nearly equal proportions of two cytochrome P-450 polypeptides that have been resolved only under denaturing conditions. Overall similarities between these polypeptides include indistinguishable amino acid compositions, similar trypsin digest patterns, and cross reactivity with the same antibody. The amino terminal sequences of both polypeptides are identical, with the exception that one of them lacks a methionine residue at the amino terminus. This sequence exhibits some similarities with the membrane targeting signal found at the amino terminus of most mammalian cytochromes P-450. Images Figure 3 PMID:16666677

  11. Changes in serum interleukin-33 levels in patients with acute cerebral infarction.

    PubMed

    Liu, Jingyao; Xing, Yingqi; Gao, Ying; Zhou, Chunkui

    2014-02-01

    Inflammation is widely considered to be involved in the pathogenesis of cerebral ischemic injury. The balance between inflammatory and anti-inflammatory factors significantly affects the prognosis of patients with cerebral infarction. Interleukin-33 (IL-33), a newly identified member of the interkeukin-1 superfamily, has been found to play very important roles in the inflammation of several human diseases including asthma, inflammatory bowel disease, and central nervous system inflammation. To our knowledge its role in the pathology of acute cerebral infarction has not yet been reported. In this study, we demonstrated that serum IL-33 levels were significantly increased in patients with acute cerebral infarction compared to control patients without acute cerebral infarction. Furthermore, serum IL-33 levels increased with the infarction volume. Our study suggests that IL-33 may be involved in the pathogenesis and/or progression of acute cerebral infarction. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. The Cerebral Palsy Research Registry: Development and Progress Toward National Collaboration in the United States

    PubMed Central

    Hurley, Donna S.; Sukal-Moulton, Theresa; Msall, Michael E.; Gaebler-Spira, Deborah; Krosschell, Kristin J.; Dewald, Julius P.

    2011-01-01

    Cerebral palsy is the most common neurodevelopmental motor disability in children. The condition requires medical, educational, social, and rehabilitative resources throughout the life span. Several countries have developed population-based registries that serve the purpose of prospective longitudinal collection of etiologic, demographic, and functional severity. The United States has not created a comprehensive program to develop such a registry. Barriers have been large population size, poor interinstitution collaboration, and decentralized medical and social systems. The Cerebral Palsy Research Registry was created to fill the gap between population and clinical-based cerebral palsy registries and promote research in the field. This is accomplished by connecting persons with cerebral palsy, as well as their families, to a network of regional researchers. This article describes the development of an expandable cerebral palsy research registry, its current status, and the potential it has to affect families and persons with cerebral palsy in the United States and abroad. PMID:21677201

  13. Characterization of Four Covalently-Linked Yeast Cytochrome c/Cytochrome c Peroxidase Complexes: Evidence for Electrostatic Interaction between Bound Cytochrome c Molecules†

    PubMed Central

    Nakani, Siddhartha; Vitello, Lidia B.; Erman, James E.

    2008-01-01

    Four covalent complexes between recombinant yeast cytochrome c and cytochrome c peroxidase (rCcP) were synthesized via disulfide bond formation using specifically designed protein mutants [Papa, H. S., and Poulos, T. L. (1995) Biochemistry 34, 6573–6580]. One of the complexes, designated V5C/K79C, has cysteine residues replacing valine-5 in rCcP and lysine-79 in cytochrome c with disulfide bond formation between these residues linking the two proteins. The V5C/K79C complex has the covalently-bound cytochrome c located on the ‘back-side’ of cytochrome c peroxidase, ~180° from the primary cytochrome c-binding site as defined by the crystallographic structure of the 1:1 non-covalent complex [Pelletier, H., and Kraut J. (1992) Science 258, 1748–1755]. Three other complexes have the covalently bound cytochrome c located ~90° from the primary binding site and are designated K12C/K79C, N78C/K79C, and K264C/K79C, respectively. Steady-state kinetic studies were used to investigate the catalytic properties of the covalent complexes at both 10 and 100 mM ionic strength, pH 7.5. All four covalent complexes have catalytic activities similar to those of rCcP (within a factor of two). A comprehensive study of the ionic strength dependence of the steady-state kinetic properties of the V5C/K79C complex provides evidence for significant electrostatic repulsion between the two cytochromes bound in the 2:1 complex at low ionic strength but that the electrostatic repulsion decreases as the ionic strength of the buffer increases. PMID:17128976

  14. Picroside II Exerts a Neuroprotective Effect by Inhibiting the Mitochondria Cytochrome C Signal Pathway Following Ischemia Reperfusion Injury in Rats.

    PubMed

    Zhang, Hongyan; Zhai, Li; Wang, Tingting; Li, Shan; Guo, Yunliang

    2017-02-01

    Stroke is a common neurodegenerative disease in the wide world, and mitochondrial defects underlie the pathogenesis of ischemia, especially during reperfusion. Picroside II, the principal active component of Picrorhiza, is a traditional Chinese medicine. Our previous study demonstrated that the best therapeutic dose and time window were injection of picroside II at a dose of 10-20 mg/kg body weight following cerebral ischemia by 1.5-2.0 h. In this paper, the neuroprotective effect and the mechanism of picroside II were investigated, as well as its involvement in antioxidant and mitochondria cytochrome C (CytC) signal pathway following ischemia reperfusion (I/R) injury in rats. After 24 h of cerebral I/R, the neurobehavioral function was measured by modified neurological severity score test; the content of reactive oxygen species in brain tissue was measured by enzyme-linked immunosorbent assay; the cerebral infarction volume was detected by TTC staining; the morphology of brain tissue was observed by hematoxylin-eosin; the apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling assay; the ultrastructure of the cortical brain tissues was observation by transmission electron microscopy; the expressions of CytC and Caspase-3 were determined by immunohistochemical assay and Western blot. The results indicated that picroside II could scavenge ROS contents, decrease the cerebral infarction volume and apoptotic cells, protect the structure of mitochondria, down-regulate the expression of CytC and Caspase-3 in cerebral I/R rats. It can be concluded that picroside II exerts a neuroprotective effect by inhibiting the mitochondria CytC signal pathway following ischemia reperfusion injury in rats.

  15. Molecular pathophysiology of cerebral edema

    PubMed Central

    Gerzanich, Volodymyr; Simard, J Marc

    2015-01-01

    Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

  16. Molecular pathophysiology of cerebral edema.

    PubMed

    Stokum, Jesse A; Gerzanich, Volodymyr; Simard, J Marc

    2016-03-01

    Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema.

  17. Purification and characterization of an NADPH-cytochrome P450 (cytochrome c) reductase from spearmint (Mentha spicata) glandular trichomes.

    PubMed

    Ponnamperuma, K; Croteau, R

    1996-05-01

    Solubilized NADPH-cytochrome c (P450) reductase was purified to homogeneity from an extract of spearmint (Mentha spicata) glandular trichomes by dye-ligand interaction chromatography on Matrex-Gel Red A and affinity chromatography on 2', 5'-adenosine diphosphate agarose. SDS-PAGE of the purified enzyme preparation revealed the presence of two similar proteins with masses of 82 kDa (major) and 77 kDa (minor) that crossreacted on immunoblot analysis with polyclonal antibodies directed against NADPH-cytochrome P450 reductase from Jerusalem artichoke and from mung bean. Complete immunoinhibition of reductase activity was observed with both types of polyclonal antibodies, while only partial inhibition of activity resulted using a family of monoclonal antibodies directed against the Jerusalem artichoke cytochrome P450 reductase. Inhibition of the spearmint oil gland cytochrome c reductase was also observed with the diphenyliodonium ion. The K(m) values for the cosubstrates NADPH and cytochrome c were 6.2 and 3.7 microM, respectively, and the pH optimum for activity was at 8.5. The NADPH-cytochrome c reductase reconstituted NADPH-dependent (-)-4S-limonene-6-hydroxylase activity in the presence of cytochrome P450, purified from the microsomal fraction of spearmint oil gland cells and dilauroyl phosphatidyl choline. These characteristics establish the identity of the purified enzyme as a NADPH-cytochrome P450 reductase.

  18. Catalytic reduction of O2 by cytochrome C using a synthetic model of cytochrome C oxidase.

    PubMed

    Collman, James P; Ghosh, Somdatta; Dey, Abhishek; Decréau, Richard A; Yang, Ying

    2009-04-15

    Cytochrome c oxidase (CcO) catalyzes the four-electron reduction of oxygen to water, the one-electron reductant Cytochrome c (Cytc) being the source of electrons. Recently we reported a functional model of CcO that electrochemically catalyzes the four-electron reduction of O(2) to H(2)O (Collman et al. Science 2007, 315, 1565). The current paper shows that the same functional CcO model catalyzes the four-electron reduction of O(2) using the actual biological reductant Cytc in a homogeneous solution. Both single and steady-state turnover kinetics studies indicate that O(2) binding is rate-determining and that O-O bond cleavage and electron transfer from reduced Cytc to the oxidized model complex are relatively fast.

  19. Local oestrogenic/androgenic balance in the cerebral vasculature.

    PubMed

    Krause, D N; Duckles, S P; Gonzales, R J

    2011-09-01

    Reproductive effects of sex steroids are well-known; however it is increasingly apparent that these hormones have important actions on non-reproductive tissues such as the vasculature. The latter effects can be relevant throughout the lifespan, not just limited to reproductive years, and are not necessarily restricted to one gender or the other. Our work has established that cerebral blood vessels are a non-reproductive target tissue for sex steroids. We have found that oestrogen and androgens alter vascular tone, endothelial function, oxidative stress and inflammatory responses in cerebral vessels. Often the actions of oestrogen and androgens oppose each other. Moreover, it is clear that cerebral vessels are directly targeted by sex steroids, as they express specific receptors for these hormones. Interestingly, cerebral blood vessels also express enzymes that metabolize sex steroids. These findings suggest that local synthesis of 17ß-estradiol and dihydrotestosterone can occur within the vessel wall. One of the enzymes present, aromatase, converts testosterone to 17ß-estradiol, which would alter the local balance of androgenic and oestrogenic influences. Thus cerebral vessels are affected by circulating sex hormones as well as locally synthesized sex steroids. The presence of vascular endocrine effector mechanisms has important implications for male-female differences in cerebrovascular function and disease. Moreover, the cerebral circulation is a target for gonadal hormones as well as anabolic steroids and therapeutic drugs used to manipulate sex steroid actions. The long-term consequences of these influences are yet to be determined.

  20. Cerebral vascular regulation and brain injury in preterm infants.

    PubMed

    Brew, Nadine; Walker, David; Wong, Flora Y

    2014-06-01

    Cerebrovascular lesions, mainly germinal matrix hemorrhage and ischemic injury to the periventricular white matter, are major causes of adverse neurodevelopmental outcome in preterm infants. Cerebrovascular lesions and neuromorbidity increase with decreasing gestational age, with the white matter predominantly affected. Developmental immaturity in the cerebral circulation, including ongoing angiogenesis and vasoregulatory immaturity, plays a major role in the severity and pattern of preterm brain injury. Prevention of this injury requires insight into pathogenesis. Cerebral blood flow (CBF) is low in the preterm white matter, which also has blunted vasoreactivity compared with other brain regions. Vasoreactivity in the preterm brain to cerebral perfusion pressure, oxygen, carbon dioxide, and neuronal metabolism is also immature. This could be related to immaturity of both the vasculature and vasoactive signaling. Other pathologies arising from preterm birth and the neonatal intensive care environment itself may contribute to impaired vasoreactivity and ineffective CBF regulation, resulting in the marked variations in cerebral hemodynamics reported both within and between infants depending on their clinical condition. Many gaps exist in our understanding of how neonatal treatment procedures and medications have an impact on cerebral hemodynamics and preterm brain injury. Future research directions for neuroprotective strategies include establishing cotside, real-time clinical reference values for cerebral hemodynamics and vasoregulatory capacity and to demonstrate that these thresholds improve long-term outcomes for the preterm infant. In addition, stimulation of vascular development and repair with growth factor and cell-based therapies also hold promise.

  1. Changes in Cerebral Oxidative Metabolism during Neonatal Seizures Following Hypoxic–Ischemic Brain Injury

    PubMed Central

    Mitra, Subhabrata; Bale, Gemma; Mathieson, Sean; Uria-Avellanal, Cristina; Meek, Judith; Tachtsidis, Ilias; Robertson, Nicola J.

    2016-01-01

    Seizures are common following hypoxic–ischemic brain injury in newborn infants. Prolonged or recurrent seizures have been shown to exacerbate neuronal damage in the developing brain; however, the precise mechanism is not fully understood. Cytochrome-c-oxidase is responsible for more than 90% of ATP production inside mitochondria. Using a novel broadband near-infrared spectroscopy system, we measured the concentration changes in the oxidation state of cerebral cytochrome-c-oxidase (Δ[oxCCO]) and hemodynamics during recurrent neonatal seizures following hypoxic–ischemic encephalopathy in a newborn infant. A rapid increase in Δ[oxCCO] was noted at the onset of seizures along with a rise in the baseline of amplitude-integrated electroencephalogram. Cerebral oxygenation and cerebral blood volume fell just prior to the seizure onset but recovered rapidly during seizures. Δ[oxCCO] during seizures correlated with changes in mean electroencephalogram voltage indicating an increase in neuronal activation and energy demand. The progressive decline in the Δ[oxCCO] baseline during seizures suggests a progressive decrease of mitochondrial oxidative metabolism. PMID:27559538

  2. Multiple modes of action of tacrolimus (FK506) for neuroprotective action on ischemic damage after transient focal cerebral ischemia in rats.

    PubMed

    Furuichi, Yasuhisa; Noto, Takahisa; Li, Ji-Yao; Oku, Takuma; Ishiye, Masayuki; Moriguchi, Akira; Aramori, Ichiro; Matsuoka, Nobuya; Mutoh, Seitaro; Yanagihara, Takehiko

    2004-07-16

    While the immunosuppressant tacrolimus (FK506) is known to be neuroprotective following cerebral ischemia, the mechanisms underlying its neuroprotective properties are not fully understood. To determine the mode of action by which tacrolimus ameliorates neurodegeneration after transient focal ischemia, we therefore evaluated the effect of tacrolimus on DNA damage, release of cytochrome c, activation of microglia and infiltration of neutrophils following a 60-min occlusion of the middle cerebral artery (MCA) in rats. In this model, cortical brain damage gradually expanded until 24 h after reperfusion, whereas brain damage in the caudate putamen was fully developed within 5 h. Tacrolimus (1 mg/kg) administered immediately after MCA occlusion significantly reduced ischemic damage in the cerebral cortex, but not in the caudate putamen. Tacrolimus decreased both apoptotic and necrotic cell death at 24 h and reduced the number of cytochrome c immunoreactive cells at 8 h after reperfusion in the ischemic penumbra in the cerebral cortex. In contrast, tacrolimus did not show significant neuroprotection for necrotic cell death and reduction of cytochrome c immunoreactive cells in the caudate putamen. Tacrolimus also significantly decreased microglial activation at 8 h and inflammatory markers (cytokine-induced neutrophil chemoattractant and myeloperoxidase [MPO] activity) at 24 h after reperfusion in the ischemic cortex but not in the caudate putamen. These results collectively suggest that tacrolimus ameliorates the gradually expanded brain damage by inhibiting both apoptotic and necrotic cell death, as well as suppressing inflammatory reactions.

  3. Structure and function of cytochrome bc complexes

    SciTech Connect

    Berry, E.A.; Guergova-Kuras, M.; Huang, Li-Shar; Crofts, A.R.

    2000-05-01

    The cytochrome bc complexes represent a phylogenetically diverse group of electron-transfer membrane protein complexes, most familiarly represented by the mitochondrial and bacterial bc1 complexes and the chloroplast and cyanobacterial b6f complex. All these complexes couple electron transfer to protein translocation across a closed lipid bilayer membrane, conserving the free energy released by the oxidation-reduction process in the form of an electrochemical proton gradient across the membrane. Recent exciting developments include the application of site-directed mutagenesis to define the role of conserved residues, and the emergence over the past 5 years of x-ray structures for several mitochondrial complexes, and for two important domains of the b6f complex.

  4. [Analysis of 58 neonatal cases with cerebral infarction].

    PubMed

    Li, Zhi-hua; Chen, Chao

    2013-01-01

    Cerebral infarction (CI) is one of severe diseases of central nervous system in neonates, and some infants with CI could have poor prognosis in the long term. This study aimed to analyze the clinical data and prognosis of all neonatal cases with cerebral infarction in recent years and to help future clinical work. Totally 58 neonatal cases with CI admitted to NICU of the hospital from January 1999 to December 2010 were included in this study. We analyzed all clinical data and prognosis by retrospective analysis. Fifty-two term babies and six preterm babies were included. There were altogether 51 cases with asphyxia and 7 with hemorrhagic cerebral infarction. Perinatal hypoxia-ischemia was the most common high-risk factor and it accounted for 46.6%. Seizure was the most frequent initial symptom and the most common clinical manifestation (accounted for 77.6%), and it was followed by intermittent cyanosis, apnea and lethargy. Cerebral CT scan and magnetic resonance imaging were major methods to help to make the diagnosis and they also had close relation with prognosis. Diffusion weighted imaging was very helpful to diagnose infarction in early stage. Left middle cerebral artery was the most common artery to be involved. Supportive therapy and symptomatic treatment were the main methods in the acute stage of neonatal cerebral infarction. Those babies with poor prognosis mostly had large infarction involving cerebral hemisphere, thalamus and basal ganglia. Neonatal cerebral infarction was a severe brain injury affecting long tern nervous system prognosis. Perinatal hypoxia was the most common high-risk factor and seizure was the most frequent initial symptom. Diffusion weighted imaging was valuable to diagnose infarction in early stage. Most of infants with poor prognosis had large infarction involving hemisphere, thalamus and basal ganglia. Early diagnosis with brain imaging would be helpful for rehabilitation therapy and improving prognosis.

  5. Flower colour and cytochromes P450.

    PubMed

    Tanaka, Yoshikazu; Brugliera, Filippa

    2013-02-19

    Cytochromes P450 play important roles in biosynthesis of flavonoids and their coloured class of compounds, anthocyanins, both of which are major floral pigments. The number of hydroxyl groups on the B-ring of anthocyanidins (the chromophores and precursors of anthocyanins) impact the anthocyanin colour, the more the bluer. The hydroxylation pattern is determined by two cytochromes P450, flavonoid 3'-hydroxylase (F3'H) and flavonoid 3',5'-hydroxylase (F3'5'H) and thus they play a crucial role in the determination of flower colour. F3'H and F3'5'H mostly belong to CYP75B and CYP75A, respectively, except for the F3'5'Hs in Compositae that were derived from gene duplication of CYP75B and neofunctionalization. Roses and carnations lack blue/violet flower colours owing to the deficiency of F3'5'H and therefore lack the B-ring-trihydroxylated anthocyanins based upon delphinidin. Successful redirection of the anthocyanin biosynthesis pathway to delphinidin was achieved by expressing F3'5'H coding regions resulting in carnations and roses with novel blue hues that have been commercialized. Suppression of F3'5'H and F3'H in delphinidin-producing plants reduced the number of hydroxyl groups on the anthocyanidin B-ring resulting in the production of monohydroxylated anthocyanins based on pelargonidin with a shift in flower colour to orange/red. Pelargonidin biosynthesis is enhanced by additional expression of a dihydroflavonol 4-reductase that can use the monohydroxylated dihydrokaempferol (the pelargonidin precursor). Flavone synthase II (FNSII)-catalysing flavone biosynthesis from flavanones is also a P450 (CYP93B) and contributes to flower colour, because flavones act as co-pigments to anthocyanins and can cause blueing and darkening of colour. However, transgenic plants expression of a FNSII gene yielded paler flowers owing to a reduction of anthocyanins because flavanones are precursors of anthocyanins and flavones.

  6. Characterization of orphan human cytochromes P450.

    PubMed

    Stark, Katarina; Guengerich, F Peter

    2007-01-01

    Of the 57 human cytochromes P450 (P450) and 58 pseudogenes discovered to date, (http://drnelson.utmem.edu/CytochromeP450.html ), 1/4 still remain "orphans" in the sense that their function, expression sites, and regulation are still largely not elucidated. The post-human genome-sequencing project era has presented the research community with novel challenges. Despite many insights gathered about gene location and genetic variations in our human genome, we still lack important knowledge about these novel P450 enzymes and their functions in endogenous and exogenous metabolism, as well as their possible roles in the metabolism of toxicants and carcinogens. Our own list of such orphans currently consists of 13 members: P450 2A7, 2S1, 2U1, 2W1, 3A43, 4A22, 4F11, 4F22, 4V2, 4X1, 4Z1, 20A1, and 27C1. Some of the orphans, e.g. P450s 2W1 and 2U1, already have putative assigned functions in arachidonic acid metabolism and may activate carcinogens. However, at this point, for the majority of them more knowledge is available about their genes and single nucleotide polymorphisms than of their biological functions. It is noteworthy that most P450 orphans express high interspecies sequence conservation and have orthologs in rodents (e.g. CYP4X1/Cyp4x1, CYP4V2/Cyp4v3). This review summarizes recent knowledge about the P450 orphans and questions remaining about their specific roles in human metabolism.

  7. Characterization of Cytochrome 579, an Unusual Cytochrome Isolated from an Iron-Oxidizing Microbial Community

    SciTech Connect

    Singer, Steven; Chan, Clara S; Zemla, Adam; Verberkmoes, Nathan C; Hwang, Mona; Hettich, Robert {Bob} L; Banfield, Jillian F.; Thelen, Michael P.

    2008-01-01

    Proteogenomic studies of Fe(II)-oxidizing microbial biofilms collected from an extremely acidic environment have identified a novel, soluble cytochrome as one of the most abundant proteins produced by these communities. This red cytochrome, extracted from biofilms with dilute sulfuric acid and purified by cation exchange chromatography, has an unusual visible spectral signature at 579 nm. Fe(II)-dependent reduction of Cyt579 was thermodynamically favorable at pH>3, raising the possibility that Cyt579 acts as an accessory protein for electron transfer. Transmission electron microscopy of immuno-gold labeled biofilm indicated that the Cyt579 is localized near the bacterial cell surface, consistent with periplasmic localization. Further protein analysis of Cyt579, using preparative chromatofocusing and SDS-PAGE, revealed three forms of the protein that correspond to different N-terminal truncations of the amino acid sequence. Intact protein analysis corroborated the post-translational modifications of these forms and identified a genomically uncharacterized Cyt579 variant. Homology modeling was used to predict the overall cytochrome structure and heme binding site; positions of nine amino acid substitutions found in 3 Cyt579 variants all map to the surface of the protein and away from the heme group. Based on this detailed characterization of Cyt579, we propose that Cyt579 acts an electron transfer protein shuttling electrons derived from Fe(II) oxidation to support critical metabolic functions in the acidophilic microbial community.

  8. The respiratory system of the marine bacterium Beneckea natriegens. I. Cytochrome composition.

    PubMed

    Weston, J A; Knowles, C J

    1974-02-22

    (1) The cytochrome composition of Beneckea natriegens grown under aerobic conditions has been examined. (2) Cell-free extracts obtained by sonication were separated into particulate and supernatant fractions by centrifugation at 150,000 x g. (3) The particulate fraction contained cytochromes b562, b557, b or c554, c549.5, c547, and low concentrations of cytochromes a1 and a2. (Subscripts refer to the wavelength optima of the b and c type cytochrome alpha-peaks in low temperature (77 degrees K) difference spectra.) Also present was a second cytochrome c549.5 which is capable of binding carbon monoxide (cytochrome c549.5(CO)) and which is also found in the supernatant fraction. (4) Reduced plus CO minus reduced difference spectra had spectral peaks corresponding to cytochrome o and two c type cytochromes, and low concentrations of cytochromes a1 and a2. (5) Action spectra for the relief of CO inhibition showed that cytochrome a2, the CO binding c type cytochrome(s) and possibly cytochrome o, but not cytochrome a1, had oxidase activity in intact cells. In cells grown to the late stationary phase, when cytochrome a2 and particularly cytochrome a1 were induced, the primary functual oxidase was cytochrome a1.

  9. Cerebral Hemodynamics and Vascular Reactivity in Mild and Severe Ischemic Rodent Middle Cerebral Artery Occlusion Stroke Models

    PubMed Central

    Sim, Jeongeun; Jo, Areum; Kang, Bok-Man; Lee, Sohee; Bang, Oh Young; Heo, Chaejeong; Jhon, Gil-Ja; Lee, Youngmi

    2016-01-01

    Ischemia can cause decreased cerebral neurovascular coupling, leading to a failure in the autoregulation of cerebral blood flow. This study aims to investigate the effect of varying degrees of ischemia on cerebral hemodynamic reactivity using in vivo real-time optical imaging. We utilized direct cortical stimulation to elicit hyper-excitable neuronal activation, which leads to induced hemodynamic changes in both the normal and middle cerebral artery occlusion (MCAO) ischemic stroke groups. Hemodynamic measurements from optical imaging accurately predict the severity of occlusion in mild and severe MCAO animals. There is neither an increase in cerebral blood volume nor in vessel reactivity in the ipsilateral hemisphere (I.H) of animals with severe MCAO. The pial artery in the contralateral hemisphere (C.H) of the severe MCAO group reacted more slowly than both hemispheres in the normal and mild MCAO groups. In addition, the arterial reactivity of the I.H in the mild MCAO animals was faster than the normal animals. Furthermore, artery reactivity is tightly correlated with histological and behavioral results in the MCAO ischemic group. Thus, in vivo optical imaging may offer a simple and useful tool to assess the degree of ischemia and to understand how cerebral hemodynamics and vascular reactivity are affected by ischemia. PMID:27358581

  10. Control of electron transfer in the cytochrome system of mitochondria by pH, transmembrane pH gradient and electrical potential. The cytochromes b-c segment.

    PubMed

    Papa, S; Lorusso, M; Izzo, G; Capuano, F

    1981-02-15

    1. A study is presented of the effects of pH, transmembrane pH gradient and electrical potential on oxidoreductions of b and c cytochromes in ox heart mitochondria and 'inside-out' submitochondrial particles. 2. Kinetic analysis shows that, in mitochondria at neutral pH, there is a restraint on the aerobic oxidation of cytochrome b566 with respect to cytochrome b562. Valinomycin plus K+ accelerates cytochrome b566 oxidation and retards net oxidation of cytochrome b562. At alkaline pH the rate of cytochrome b566 oxidation approaches that of cytochrome b562 and the effects of valinomycin on b cytochromes are impaired. 3. At slightly acidic pH, oxygenation of antimycin-supplemented mitochondria causes rapid reduction of cytochrome b566 and small delayed reduction of cytochrome b562. Valinomycin or a pH increase in the medium promote reduction of cytochrome b562 and decrease net reduction of cytochrome b566. 4. Addition of valinomycin to mitochondria and submitochondrial particles in the respiring steady state causes, at pH values around neutrality, preferential oxidation of cytochrome b566 with respect to cytochrome b562. The differential effect of valinomycin on oxidation of cytochromes b566 and b562 is enhanced by substitution of 1H2O of the medium with 2H2O and tends to disappear as the pH of the medium is raised to alkaline values. 5. Nigericin addition in the aerobic steady state causes, both in mitochondria and submitochondrial particles, preferential oxidation of cytochrome b562 with respect to cytochrome b566. This is accompanied by c cytochrome oxidation in mitochondria but c cytochrome reduction in submitochondrial particles. 6. In mitochondria as well as in submitochondrial particles, the aerobic transmembrane potential (delta psi) does not change by raising the pH of the external medium from neutrality to alkalinity. The transmembrane pH gradient (delta pH) on the other hand, decrease slightly. 7. The results presented provide evidence that the delta psi

  11. Control of electron transfer in the cytochrome system of mitochondria by pH, transmembrane pH gradient and electrical potential. The cytochromes b-c segment.

    PubMed Central

    Papa, S; Lorusso, M; Izzo, G; Capuano, F

    1981-01-01

    1. A study is presented of the effects of pH, transmembrane pH gradient and electrical potential on oxidoreductions of b and c cytochromes in ox heart mitochondria and 'inside-out' submitochondrial particles. 2. Kinetic analysis shows that, in mitochondria at neutral pH, there is a restraint on the aerobic oxidation of cytochrome b566 with respect to cytochrome b562. Valinomycin plus K+ accelerates cytochrome b566 oxidation and retards net oxidation of cytochrome b562. At alkaline pH the rate of cytochrome b566 oxidation approaches that of cytochrome b562 and the effects of valinomycin on b cytochromes are impaired. 3. At slightly acidic pH, oxygenation of antimycin-supplemented mitochondria causes rapid reduction of cytochrome b566 and small delayed reduction of cytochrome b562. Valinomycin or a pH increase in the medium promote reduction of cytochrome b562 and decrease net reduction of cytochrome b566. 4. Addition of valinomycin to mitochondria and submitochondrial particles in the respiring steady state causes, at pH values around neutrality, preferential oxidation of cytochrome b566 with respect to cytochrome b562. The differential effect of valinomycin on oxidation of cytochromes b566 and b562 is enhanced by substitution of 1H2O of the medium with 2H2O and tends to disappear as the pH of the medium is raised to alkaline values. 5. Nigericin addition in the aerobic steady state causes, both in mitochondria and submitochondrial particles, preferential oxidation of cytochrome b562 with respect to cytochrome b566. This is accompanied by c cytochrome oxidation in mitochondria but c cytochrome reduction in submitochondrial particles. 6. In mitochondria as well as in submitochondrial particles, the aerobic transmembrane potential (delta psi) does not change by raising the pH of the external medium from neutrality to alkalinity. The transmembrane pH gradient (delta pH) on the other hand, decrease slightly. 7. The results presented provide evidence that the delta psi

  12. Visual function and perinatal focal cerebral infarction.

    PubMed Central

    Mercuri, E; Atkinson, J; Braddick, O; Anker, S; Nokes, L; Cowan, F; Rutherford, M; Pennock, J; Dubowitz, L

    1996-01-01

    AIMS: To evaluate the visual function of infants with perinatal cerebral infarction in whom the site and size of the lesion has been determined using magnetic resonance imaging (MRI). METHODS: Twelve infants with cerebral infarction on MRI were studied with a battery of tests specifically designed to evaluate visual function in infancy. This included tests: for visual attention (fixation shifts); of cerebral asymmetry (optokinetic nystagmus, visual fields); for assessment of acuity (forced choice preferential looking); and neurophysiological measures of vision (phase reversal and orientation reversal visual evoked potential). RESULTS: A considerable incidence of abnormalities on at least one of the tests for visual function used was observed. The presence or severity of visual abnormalities could not always be predicted by the site and extent of the lesion seen on imaging. CONCLUSIONS: Early focal lesions affecting the visual pathway can, to some extent, be compensated for by the immature developing brain. These data suggest that all the infants presenting with focal lesions need to be investigated with a detailed assessment of various aspects of vision. Images PMID:8949687

  13. Antithrombotic therapy in patients with cerebral microbleeds.

    PubMed

    Wilson, Duncan; Werring, David J

    2017-02-01

    Cerebral microbleeds (CMBs) are a radiological marker of cerebral small vessel disease corresponding to small haemosiderin foci identified by blood-sensitive MRI. CMBs are common in older community populations, and in individuals with ischaemic stroke or transient ischaemic attack (TIA), and intracerebral haemorrhage (ICH). We summarize how CMBs might contribute to assessing the future risk of ischaemic stroke and ICH to inform antithrombotic (antiplatelet or anticoagulant) decisions. CMBs are a risk factor for future ischaemic stroke and ICH in all community and hospital populations studied. Following ischaemic stroke/TIA treated with antithrombotics, increasing CMB burden increases the risk of ICH more steeply than that of ischaemic stroke. In ICH populations the risk of recurrent ICH increases with CMB burden, and is highest in those with strictly lobar CMBs or other haemorrhagic findings (e.g. cortical superficial siderosis) suggesting cerebral amyloid angiopathy (CAA). In ischaemic stroke or patients with TIA less than five CMBs should not affect antithrombotic decisions, although with more than five CMBs the risks of future ICH and ischaemic stroke are finely balanced, and antithrombotics might cause net harm. In lobar ICH populations, a high burden of strictly lobar CMBs is associated with CAA and high ICH risk; antithrombotics should be avoided unless there is a compelling indication.

  14. Middle Cerebral Artery Calcification

    PubMed Central

    Kao, Hung-Wen; Liou, Michelle; Chung, Hsiao-Wen; Liu, Hua-Shan; Tsai, Ping-Huei; Chiang, Shih-Wei; Chou, Ming-Chung; Peng, Giia-Sheun; Huang, Guo-Shu; Hsu, Hsian-He; Chen, Cheng-Yu

    2015-01-01

    Abstract Calcification of the middle cerebral artery (MCA) is uncommon in the healthy elderly. Whether calcification of the MCA is associated with cerebral ischemic stroke remains undetermined. We intended to investigate the association using Agatston calcium scoring of the MCA. This study retrospectively included 354 subjects with ischemic stroke in the MCA territory and 1518 control subjects who underwent computed tomography (CT) of the brain. We recorded major known risk factors for ischemic stroke, including age, gender, hypertension, diabetes mellitus, smoking, hyperlipidemia, and obesity, along with the MCA calcium burden, measured with the Agatston calcium scoring method. Univariate and modified logistic regression analyses were performed to examine the association between the MCA calcification and ischemic stroke. The univariate analyses showed significant associations of ischemic stroke with age, hypertension, diabetes mellitus, smoking, total MCA Agatston score, and the presence of calcification on both or either side of the MCA. Subjects with the presence of MCA calcification on both or either side of the MCA were 8.46 times (95% confidence interval, 4.93–14.53; P < 0.001) more likely to have a cerebral infarct than subjects without MCA calcification after adjustment for the major known risk factors, including age, hypertension, diabetes mellitus, and smoking. However, a higher degree of MCA calcification reflected by the Agatston score was not associated with higher risk of MCA ischemic stroke after adjustment for the confounding factors and presence of MCA calcification. These results suggest that MCA calcification is associated with ischemic stroke in the MCA territory. Further prospective studies are required to verify the clinical implications of the MCA calcification. PMID:26683969

  15. [Reversible cerebral vasoconstriction syndrome].

    PubMed

    Néel, A; Guillon, B; Auffray-Calvier, E; Hello, M; Hamidou, M

    2012-10-01

    The reversible cerebral vasoconstriction syndrome (RCVS) is an under-estimated transient acute cerebrovascular disorder. It has long been mistaken as central nervous system vasculitis whereas it is now believed to result from an acute but prolonged vasospasm of cerebral arteries. This disorder can be precipitated by postpartum or vasoactive drug. However, it occurs spontaneously in a significant number of cases. The characteristic clinico-radiological presentation and disease course of the RCVS has been delineated only recently. Mean age at onset is 40-45 years, with a female predominance. A provocative factor can be identified in 12-60% out of the patients. Clinical presentation is predominantly marked by recurrent thunderclap headaches, but can be complicated with focal neurological deficit or seizures. Brain imaging is normal in most cases, but can reveal hemorrhagic or ischemic complications. Cortical subarachnoid hemorrhage is a suggestive finding. A posterior reversible encephalopathy syndrome (PRES) can be seen occasionally. Cerebral angiography reveals multifocal arterial narrowing with string and bead appearance. Cerebrospinal fluid reveals no or mild abnormalities. The disease resumes spontaneously within several days to weeks, whereas vasoconstriction reverses within 1 to 3 months. This clinico-radiological presentation should be promptly recognized in order to avoid unnecessary investigations and aggressive treatment, and lead to search for a triggering factor. Further studies are required in order to clarify the precipitating role of several drugs, and clinical trials are needed to reduce the occurrence of strokes. Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  16. Orthostatic Cerebral Hypoperfusion Syndrome.

    PubMed

    Novak, Peter

    2016-01-01

    Orthostatic dizziness without orthostatic hypotension is common but underlying pathophysiology is poorly understood. This study describes orthostatic cerebral hypoperfusion syndrome (OCHOs). OCHOs is defined by (1) abnormal orthostatic drop of cerebral blood flow velocity (CBFv) during the tilt test and (2) absence of orthostatic hypotension, arrhythmia, vascular abnormalities, or other causes of abnormal orthostatic CBFv. This retrospective study included patients referred for evaluation of unexplained orthostatic dizziness. Patients underwent standardized autonomic testing, including 10 min of tilt test. The following signals were monitored: heart rate, end tidal CO2, blood pressure, and CBFv from the middle cerebral artery using transcranial Doppler. Patients were screened for OCHOs. Patients who fulfilled the OCHOs criteria were compared to age- and gender-matched controls. From 1279 screened patients, 102 patients (60/42 women/men, age 51.1 ± 14.9, range 19-84 years) fulfilled criteria of OCHOs. There was no difference in baseline supine hemodynamic variables between OCHOs and the control group. During the tilt, mean CBFv decreased 24.1 ± 8.2% in OCHOs versus 4.2 ± 5.6% in controls (p < 0.0001) without orthostatic hypotension in both groups. Supine mean blood pressure (OCHOs/controls, 90.5 ± 10.6/91.1 ± 9.4 mmHg, p = 0.62) remained unchanged during the tilt (90.4 ± 9.7/92.1 ± 9.6 mmHg, p = 0.2). End tidal CO2 and heart rate responses to the tilt were normal and equal in both groups. OCHOs is a novel syndrome of low orthostatic CBFv. Two main pathophysiological mechanisms are proposed, including active cerebral vasoconstriction and passive increase of peripheral venous compliance. OCHOs may be a common cause of orthostatic dizziness.

  17. Resting cerebral blood flow

    PubMed Central

    Ances, B M.; Sisti, D; Vaida, F; Liang, C L.; Leontiev, O; Perthen, J E.; Buxton, R B.; Benson, D; Smith, D M.; Little, S J.; Richman, D D.; Moore, D J.; Ellis, R J.

    2009-01-01

    Objective: HIV enters the brain soon after infection causing neuronal damage and microglial/astrocyte dysfunction leading to neuropsychological impairment. We examined the impact of HIV on resting cerebral blood flow (rCBF) within the lenticular nuclei (LN) and visual cortex (VC). Methods: This cross-sectional study used arterial spin labeling MRI (ASL-MRI) to measure rCBF within 33 HIV+ and 26 HIV− subjects. Nonparametric Wilcoxon rank sum test assessed rCBF differences due to HIV serostatus. Classification and regression tree (CART) analysis determined optimal rCBF cutoffs for differentiating HIV serostatus. The effects of neuropsychological impairment and infection duration on rCBF were evaluated. Results: rCBF within the LN and VC were significantly reduced for HIV+ compared to HIV− subjects. A 2-tiered CART approach using either LN rCBF ≤50.09 mL/100 mL/min or LN rCBF >50.09 mL/100 mL/min but VC rCBF ≤37.05 mL/100 mL/min yielded an 88% (29/33) sensitivity and an 88% (23/26) specificity for differentiating by HIV serostatus. HIV+ subjects, including neuropsychologically unimpaired, had reduced rCBF within the LN (p = 0.02) and VC (p = 0.001) compared to HIV− controls. A temporal progression of brain involvement occurred with LN rCBF significantly reduced for both acute/early (<1 year of seroconversion) and chronic HIV-infected subjects, whereas rCBF in the VC was diminished for only chronic HIV-infected subjects. Conclusion: Resting cerebral blood flow (rCBF) using arterial spin labeling MRI has the potential to be a noninvasive neuroimaging biomarker for assessing HIV in the brain. rCBF reductions that occur soon after seroconversion possibly reflect neuronal or vascular injury among HIV+ individuals not yet expressing neuropsychological impairment. GLOSSARY AEH = acute/early HIV infection; ANOVA = analysis of variance; ASL-MRI = arterial spin labeling MRI; CART = classification and regression tree; CBF = cerebral blood flow; CH = chronic HIV

  18. Oligodendrogenesis after cerebral ischemia

    PubMed Central

    Zhang, Ruilan; Chopp, Michael; Zhang, Zheng Gang

    2013-01-01

    Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle of adult rodent brain generate oligodendrocyte progenitor cells (OPCs) that disperse throughout the corpus callosum and striatum where some of OPCs differentiate into mature oligodendrocytes. Studies in animal models of stroke demonstrate that cerebral ischemia induces oligodendrogenesis during brain repair processes. This article will review evidence of stroke-induced proliferation and differentiation of OPCs that are either resident in white matter or are derived from SVZ neural progenitor cells and of therapies that amplify endogenous oligodendrogenesis in ischemic brain. PMID:24194700

  19. Mimicking a SURF1 allele reveals uncoupling of cytochrome c oxidase assembly from translational regulation in yeast.

    PubMed

    Reinhold, Robert; Bareth, Bettina; Balleininger, Martina; Wissel, Mirjam; Rehling, Peter; Mick, David U

    2011-06-15

    Defects in mitochondrial energy metabolism lead to severe human disorders, mainly affecting tissues especially dependent on oxidative phosphorylation, such as muscle and brain. Leigh Syndrome describes a severe encephalomyopathy in infancy, frequently caused by mutations in SURF1. SURF1, termed Shy1 in Saccharomyces cerevisiae, is a conserved assembly factor for the terminal enzyme of the respiratory chain, cytochrome c oxidase. Although the molecular function of SURF1/Shy1 is still enigmatic, loss of function leads to cytochrome c oxidase deficiency and reduced expression of the central subunit Cox1 in yeast. Here, we provide insights into the molecular mechanisms leading to disease through missense mutations in codons of the most conserved amino acids in SURF1. Mutations affecting G(124) do not compromise import of the SURF1 precursor protein but lead to fast turnover of the mature protein within the mitochondria. Interestingly, an Y(274)D exchange neither affects stability nor localization of the protein. Instead, SURF1(Y274D) accumulates in a 200 kDa cytochrome c oxidase assembly intermediate. Using yeast as a model, we demonstrate that the corresponding Shy1(Y344D) is able to overcome the stage where cytochrome c oxidase assembly links to the feedback regulation of mitochondrial Cox1 expression. However, Shy1(Y344D) impairs the assembly at later steps, most apparent at low temperature and exhibits a dominant-negative phenotype upon overexpression. Thus, exchanging the conserved tyrosine (Y(344)) with aspartate in yeast uncouples translational regulation of Cox1 from cytochrome c oxidase assembly and provides evidence for the dual functionality of Shy1.

  20. Multilayered polyelectrolyte microcapsules: interaction with the enzyme cytochrome C oxidase.

    PubMed

    Pastorino, Laura; Dellacasa, Elena; Noor, Mohamed R; Soulimane, Tewfik; Bianchini, Paolo; D'Autilia, Francesca; Antipov, Alexei; Diaspro, Alberto; Tofail, Syed A M; Ruggiero, Carmelina

    2014-01-01

    Cell-sized polyelectrolyte capsules functionalized with a redox-driven proton pump protein were assembled for the first time. The interaction of polyelectrolyte microcapsules, fabricated by electrostatic layer-by-layer assembly, with cytochrome c oxidase molecules was investigated. We found that the cytochrome c oxidase retained its functionality, that the functionalized microcapsules interacting with cytochrome c oxidase were permeable and that the permeability characteristics of the microcapsule shell depend on the shell components. This work provides a significant input towards the fabrication of an integrated device made of biological components and based on specific biomolecular functions and properties.

  1. [Acute tetraparesis of cerebral origin].

    PubMed

    Feuillet, L; Milandre, L; Kaphan, E; Ali Cherif, A

    2005-09-01

    Thrombolytic treatment in the early stage of ischemic cerebral attacks requires rapid confirmation of the diagnosis and topographic localization. Unusual clinical features can lead to misdiagnosis with the risk of delaying optimal therapeutic management. We report the cases of two patients who experienced acute tetraparesis without any associated encephalic sign, consistent with the diagnosis of spinal cord injury. Cervical magnetic resonance imaging (MRI) was normal. Conversely, cerebral MRI displayed in both cases bilateral hemispheric infarction. Two ischemic lesions were revealed in the territory of both anterior cerebral arteries in the first patient, while the second patient had a bilateral infarction in the posterior arms of both internal capsules. In case of tetraparesis, emergency spinal cord MRI should be performed to rule out neurosurgical etiologies and ischemia. If negative, cerebral MRI should be performed at the same time to look for early cerebral infarction in both hemispheres and determine the indication for thrombolysis.

  2. Uncommon Causes of Cerebral Microbleeds.

    PubMed

    Noorbakhsh-Sabet, Nariman; Pulakanti, Varun Chandi; Zand, Ramin

    2017-10-01

    Cerebral microbleeds (CMBs) are small and round perivascular hemosiderin depositions detectable by gradient echo sequences or susceptibility-weighted imaging. Cerebral microbleeds are common among patients with hypertension, cerebral ischemia, or cerebral amyloid angiopathy. In this article, we describe uncommon causes of CMBs. We searched Pubmed with the keyword CMBs for relevant studies and looked for different uncommon causes of CMBs. CMBs have several uncommon etiologies including posterior reversible encephalopathy syndrome, infective endocarditis, brain radiation therapy, cocaine abuse, thrombotic thrombocytopenic purpura, traumatic brain injury, intravascular lymphomatosis or proliferating angio-endotheliomatosis, moyamoya disease, sickle cell anemia/β-thalassemia, cerebral autosomal dominant arteriopathy subcortical infarcts, and leukoencephalopathy (CADASIL), genetic syndromes, or obstructive sleep apnea. Understanding the uncommon causes of CMBs is not only helpful in diagnosis and prognosis of some of these rare diseases, but can also help in better understanding different pathophysiology involved in the development of CMBs. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  3. Metabolic engineering of light-driven cytochrome P450 dependent pathways into Synechocystis sp. PCC 6803.

    PubMed

    Wlodarczyk, Artur; Gnanasekaran, Thiyagarajan; Nielsen, Agnieszka Zygadlo; Zulu, Nodumo Nokolunga; Mellor, Silas Busck; Luckner, Manja; Thøfner, Jens Frederik Bang; Olsen, Carl Erik; Mottawie, Mohammed Saddik; Burow, Meike; Pribil, Mathias; Feussner, Ivo; Møller, Birger Lindberg; Jensen, Poul Erik

    2016-01-01

    Solar energy provides the energy input for the biosynthesis of primary and secondary metabolites in plants and other photosynthetic organisms. Some secondary metabolites are high value compounds, and typically their biosynthesis requires the involvement of cytochromes P450s. In this proof of concept work, we demonstrate that the cyanobacterium Synechocystis sp. PCC 6803 is an eminent heterologous host for expression of metabolically engineered cytochrome P450-dependent pathways exemplified by the dhurrin pathway from Sorghum bicolor comprising two membrane bound cytochromes P450s (CYP79A1 and CYP71E1) and a soluble glycosyltransferase (UGT85B1). We show that it is possible to express multiple genes incorporated into a bacterial-like operon by using a self-replicating expression vector in cyanobacteria. We demonstrate that eukaryotic P450s that typically reside in the endoplasmic reticulum membranes can be inserted in the prokaryotic membranes without affecting thylakoid membrane integrity. Photosystem I and ferredoxin replaces the native P450 oxidoreductase enzyme as an efficient electron donor for the P450s both in vitro and in vivo. The engineered strains produced up to 66mg/L of p-hydroxyphenylacetaldoxime and 5mg/L of dhurrin in lab-scale cultures after 3 days of cultivation and 3mg/L of dhurrin in V-shaped photobioreactors under greenhouse conditions after 9 days cultivation. All the metabolites were found to be excreted to the growth media facilitating product isolation.

  4. Spaceflight Effects on Cytochrome P450 Content in Mouse Liver

    PubMed Central

    Moskaleva, Natalia; Moysa, Alexander; Novikova, Svetlana; Tikhonova, Olga; Zgoda, Victor; Archakov, Alexander

    2015-01-01

    Hard conditions of long-term manned spaceflight can affect functions of many biological systems including a system of drug metabolism. The cytochrome P450 (CYP) superfamily plays a key role in the drug metabolism. In this study we examined the hepatic content of some P450 isoforms in mice exposed to 30 days of space flight and microgravity. The CYP content was established by the mass-spectrometric method of selected reaction monitoring (SRM). Significant changes in the CYP2C29, CYP2E1 and CYP1A2 contents were detected in mice of the flight group compared to the ground control group. Within seven days after landing and corresponding recovery period changes in the content of CYP2C29 and CYP1A2 returned to the control level, while the CYP2E1 level remained elevated. The induction of enzyme observed in the mice in the conditions of the spaceflight could lead to an accelerated biotransformation and change in efficiency of pharmacological agents, metabolizing by corresponding CYP isoforms. Such possibility of an individual pharmacological response to medication during long-term spaceflights and early period of postflight adaptation should be taken into account in space medicine. PMID:26561010

  5. Early Structural Evolution of Native Cytochrome c after Solvent Removal

    PubMed Central

    Steinberg, Michal Z.; Elber, Ron; McLafferty, Fred W.; Gerber, R. Benny; Breuker, Kathrin

    2009-01-01

    Electrospray ionization transfers thermally labile biomolecules, such as proteins, from solution into the gas phase, where they can be studied by mass spectrometry. Covalent bonds are generally preserved during and after the phase transition, but it is less clear to what extent noncovalent interactions are affected by the new gaseous environment. Here, we present atomic-level computational data on the structural rearrangement of native cytochrome c immediately after solvent removal. The first structural changes after desolvation occur surprisingly early, on a timescale of picoseconds. For the time segment of up to 4.2 ns investigated here, we observed no significant breaking of native noncovalent bonds; instead, we found formation of new noncovalent bonds. This generally involves charged residues on the protein surface, resulting in transiently stabilized intermediate structures with a global fold that is essentially the same as that in solution. Comparison with data from native electron capture dissociation experiments corroborates both its mechanistic postulations and our computational predictions, and suggests that global structural changes take place on a millisecond timescale not covered by our simulations. PMID:18785672

  6. Ab initio dynamics of the cytochrome P450 hydroxylation reaction

    PubMed Central

    Elenewski, Justin E.; Hackett, John C

    2015-01-01

    The iron(IV)-oxo porphyrin π-cation radical known as Compound I is the primary oxidant within the cytochromes P450, allowing these enzymes to affect the substrate hydroxylation. In the course of this reaction, a hydrogen atom is abstracted from the substrate to generate hydroxyiron(IV) porphyrin and a substrate-centered radical. The hydroxy radical then rebounds from the iron to the substrate, yielding the hydroxylated product. While Compound I has succumbed to theoretical and spectroscopic characterization, the associated hydroxyiron species is elusive as a consequence of its very short lifetime, for which there are no quantitative estimates. To ascertain the physical mechanism underlying substrate hydroxylation and probe this timescale, ab initio molecular dynamics simulations and free energy calculations are performed for a model of Compound I catalysis. Semiclassical estimates based on these calculations reveal the hydrogen atom abstraction step to be extremely fast, kinetically comparable to enzymes such as carbonic anhydrase. Using an ensemble of ab initio simulations, the resultant hydroxyiron species is found to have a similarly short lifetime, ranging between 300 fs and 3600 fs, putatively depending on the enzyme active site architecture. The addition of tunneling corrections to these rates suggests a strong contribution from nuclear quantum effects, which should accelerate every step of substrate hydroxylation by an order of magnitude. These observations have strong implications for the detection of individual hydroxylation intermediates during P450 catalysis. PMID:25681906

  7. Amperometric cytochrome c3-based biosensor for chromate determination.

    PubMed

    Michel, Caroline; Battaglia-Brunet, Fabienne; Minh, Canh Tran; Bruschi, Mireille; Ignatiadis, Ioannis

    2003-12-15

    The chromate reductase activity of cytochrome c(3) (Cyt c(3), M(r) 13000), isolated from the sulfate-reducing bacterium Desulfomicrobium norvegicum, was used to develop an amperometric biosensor to measure chromate (CrO(4)(2-)) bioavailability. The performance of various biosensor configurations for qualitative and quantitative determination of Cr(VI) was studied. Biosensor properties depend on the technique used to immobilize the enzyme on the electrode (glassy carbon electrode). Immobilization of Cyt c(3) by entrapment in poly 3,4-ethylenedioxythiophene films denatured the enzyme, while application of an adsorption technique did not affect enzyme activity but the detection range was limited. The best results were obtained with dialysis membranes, which allowed the determination of Cr(VI) from 0.20 to 6.84 mg l(-1) (3.85-132 microM) with a sensitivity of 35 nA mg(-1) l (1.82 nA microM(-1)). No interference was observed with As(V), As(III) and Fe(III). Only a small amount of Cyt c(3) (372 ng of protein) was needed for this biosensor.

  8. Interactions of phospholipase D and cytochrome P450 protein stability

    SciTech Connect

    Zangar, Richard C.; Fan, Yang-Yi; Chapkin, Robert S.

    2004-08-01

    Previous studies have suggested a relationship between cytochrome P450 (P450) 3A (CYP3A) conformation and the phospholipid composition of the associated membrane. In this study, we utilized a novel microsomal incubation system that mimics many of the characteristics of CYP3A degradation pathway that have been observed in vivo and in cultured cells to study the effects of phospholipid composition on protein stability. We found that addition of phosphatidylcholine-specific phospholipase D (PLD) stabilized CYP3A in this system, but that phosphatidylinositol-specific phospholipase C (PLC) was without effect. Addition of phosphatidic acid also stabilized CYP3A protein in the microsomes. The use of 1,10-phenanthroline (phenanthroline), an inhibitor of PLD activity, decreased CYP3A stability in incubated microsomes. Similarly, 6-h treatment of primary cultures of rat hepatocytes with phenanthroline resulted in nearly complete loss of CYP3A protein. Treatment of rats with nicardipine or dimethylsulfoxide (DMSO), which have been shown to affect CYP3A stability, altered the phospholipid composition of hepatic microsomes. It did not appear, though, that the changes in phospholipid composition that resulted from these in vivo treatments accounted for the change in CYP3A stability observed in hepatic microsomes from these animals.

  9. Direct observation of vibrational energy flow in cytochrome c.

    PubMed

    Fujii, Naoki; Mizuno, Misao; Mizutani, Yasuhisa

    2011-11-10

    Vibrational energy flow in ferric cytochrome c has been examined by picosecond time-resolved anti-Stokes ultraviolet resonance Raman (UVRR) measurements. By taking advantage of the extremely short nonradiative excited state lifetime of heme in the protein (< ps), excess vibrational energy of 20000-25000 cm(-1) was optically deposited selectively at the heme site. Subsequent energy relaxation in the protein moiety was investigated by monitoring the anti-Stokes UVRR intensities of the Trp59 residue, which is a single tryptophan residue involved in the protein that is located close to the heme group. It was found from temporal changes of the anti-Stokes UVRR intensities that the energy flow from the heme to Trp59 and the energy release from Trp59 took place with the time constants of 1-3 and ~8 ps, respectively. These data are consistent with the time constants for the vibrational relaxation of the heme and heating of water reported for hemeproteins. The kinetics of the energy flow were not affected by the amount of excess energy deposited at the heme group. These results demonstrate that the present technique is a powerful tool for studying the vibrational energy flow in proteins.

  10. Ab initio dynamics of the cytochrome P450 hydroxylation reaction

    NASA Astrophysics Data System (ADS)

    Elenewski, Justin E.; Hackett, John C.

    2015-02-01

    The iron(IV)-oxo porphyrin π-cation radical known as Compound I is the primary oxidant within the cytochromes P450, allowing these enzymes to affect the substrate hydroxylation. In the course of this reaction, a hydrogen atom is abstracted from the substrate to generate hydroxyiron(IV) porphyrin and a substrate-centered radical. The hydroxy radical then rebounds from the iron to the substrate, yielding the hydroxylated product. While Compound I has succumbed to theoretical and spectroscopic characterization, the associated hydroxyiron species is elusive as a consequence of its very short lifetime, for which there are no quantitative estimates. To ascertain the physical mechanism underlying substrate hydroxylation and probe this timescale, ab initio molecular dynamics simulations and free energy calculations are performed for a model of Compound I catalysis. Semiclassical estimates based on these calculations reveal the hydrogen atom abstraction step to be extremely fast, kinetically comparable to enzymes such as carbonic anhydrase. Using an ensemble of ab initio simulations, the resultant hydroxyiron species is found to have a similarly short lifetime, ranging between 300 fs and 3600 fs, putatively depending on the enzyme active site architecture. The addition of tunneling corrections to these rates suggests a strong contribution from nuclear quantum effects, which should accelerate every step of substrate hydroxylation by an order of magnitude. These observations have strong implications for the detection of individual hydroxylation intermediates during P450 catalysis.

  11. Ab initio dynamics of the cytochrome P450 hydroxylation reaction

    SciTech Connect

    Elenewski, Justin E.; Hackett, John C

    2015-02-14

    The iron(IV)-oxo porphyrin π-cation radical known as Compound I is the primary oxidant within the cytochromes P450, allowing these enzymes to affect the substrate hydroxylation. In the course of this reaction, a hydrogen atom is abstracted from the substrate to generate hydroxyiron(IV) porphyrin and a substrate-centered radical. The hydroxy radical then rebounds from the iron to the substrate, yielding the hydroxylated product. While Compound I has succumbed to theoretical and spectroscopic characterization, the associated hydroxyiron species is elusive as a consequence of its very short lifetime, for which there are no quantitative estimates. To ascertain the physical mechanism underlying substrate hydroxylation and probe this timescale, ab initio molecular dynamics simulations and free energy calculations are performed for a model of Compound I catalysis. Semiclassical estimates based on these calculations reveal the hydrogen atom abstraction step to be extremely fast, kinetically comparable to enzymes such as carbonic anhydrase. Using an ensemble of ab initio simulations, the resultant hydroxyiron species is found to have a similarly short lifetime, ranging between 300 fs and 3600 fs, putatively depending on the enzyme active site architecture. The addition of tunneling corrections to these rates suggests a strong contribution from nuclear quantum effects, which should accelerate every step of substrate hydroxylation by an order of magnitude. These observations have strong implications for the detection of individual hydroxylation intermediates during P450 catalysis.

  12. Isolation and Characterization of a Hybrid Respiratory Supercomplex Consisting of Mycobacterium tuberculosis Cytochrome bcc and Mycobacterium smegmatis Cytochrome aa3.

    PubMed

    Kim, Mi-Sun; Jang, Jichan; Ab Rahman, Nurlilah Binte; Pethe, Kevin; Berry, Edward A; Huang, Li-Shar

    2015-06-05

    Recently, energy production pathways have been shown to be viable antitubercular drug targets to combat multidrug-resistant tuberculosis and eliminate pathogen in the dormant state. One family of drugs currently under development, the imidazo[1,2-a]pyridine derivatives, is believed to target the pathogen's homolog of the mitochondrial bc1 complex. This complex, denoted cytochrome bcc, is highly divergent from mitochondrial Complex III both in subunit structure and inhibitor sensitivity, making it a good target for drug development. There is no soluble cytochrome c in mycobacteria to transport electrons from the bcc complex to cytochrome oxidase. Instead, the bcc complex exists in a "supercomplex" with a cytochrome aa3-type cytochrome oxidase, presumably allowing direct electron transfer. We describe here purification and initial characterization of the mycobacterial cytochrome bcc-aa3 supercomplex using a strain of M. smegmatis that has been engineered to express the M. tuberculosis cytochrome bcc. The resulting hybrid supercomplex is stable during extraction and purification in the presence of dodecyl maltoside detergent. It is hoped that this purification procedure will potentiate functional studies of the complex as well as crystallographic studies of drug binding and provide structural insight into a third class of the bc complex superfamily.

  13. First Case of Human Cerebral Taenia martis Cysticercosis.

    PubMed

    Brunet, Julie; Benoilid, Aurélien; Kremer, Stéphane; Dalvit, Constanza; Lefebvre, Nicolas; Hansmann, Yves; Chenard, Marie-Pierre; Mathieu, Bruno; Grimm, Felix; Deplazes, Peter; Pfaff, Alexander W; Abou-Bacar, Ahmed; Marescaux, Christian; Candolfi, Ermanno

    2015-08-01

    Taenia martis is a tapeworm affecting mustelids, with rodents serving as intermediate hosts. The larval stage (cysticercus) has been found before only rarely in humans or primates. We hereby describe a case of cerebral T. martis cysticercosis in a French immunocompetent patient, confirmed by DNA analyses of biopsy material.

  14. Kienböck's disease in cerebral palsy.

    PubMed

    Rooker, G D; Goodfellow, J W

    1977-08-01

    Five cases of Kienböck's disease occurring in a group of fifty-three adults with cerebral palsy are described. The increased incidence of the disease is attributed to the flexed posture habitual in the affected wrist and to an effect on the pattern of blood supply to the lunate.

  15. First Case of Human Cerebral Taenia martis Cysticercosis

    PubMed Central

    Benoilid, Aurélien; Kremer, Stéphane; Dalvit, Constanza; Lefebvre, Nicolas; Hansmann, Yves; Chenard, Marie-Pierre; Mathieu, Bruno; Grimm, Felix; Deplazes, Peter; Pfaff, Alexander W.; Abou-Bacar, Ahmed; Marescaux, Christian; Candolfi, Ermanno

    2015-01-01

    Taenia martis is a tapeworm affecting mustelids, with rodents serving as intermediate hosts. The larval stage (cysticercus) has been found before only rarely in humans or primates. We hereby describe a case of cerebral T. martis cysticercosis in a French immunocompetent patient, confirmed by DNA analyses of biopsy material. PMID:26019196

  16. Cytochrome c and SDS: a molten globule protein with altered axial ligation.

    PubMed

    Bertini, Ivano; Turano, Paola; Vasos, Paul R; Bondon, Arnaud; Chevance, Soizic; Simonneaux, Gérard

    2004-02-13

    Saccharomices cerevisiae (yeast iso-1) cytochrome c has been investigated in the presence of 100 mM SDS in order to simulate the interaction of cytochrome c with membrane. Under these circumstances, a high spin species with detached methionine axial ligand is observed through NMR, in analogy to findings on the horse heart protein. However, at variance with the latter system, for the yeast protein also a low spin species is detected, which appears to be present with a concentration of about 40% with respect to that of the high spin species. The R(1), R(2), [1H]-15N NOE of backbone amides which are not affected by paramagnetism are homogeneous and allow a simultaneous analysis of the data for the two species. The result is that the rotational correlation time is larger than in water and larger than expected on the basis of viscosity of the SDS-containing solution. This finding suggests interactions of cytochrome c with SDS. Furthermore, it appears that there is subnanosecond backbone mobility, which also accounts for the decreased intensity of NOE cross-peaks and may be associated with equilibria between helical and random coil structure. The dynamic behavior appears to be a common feature of the high spin and low spin species and is consistent with the presence of a molten globule state. The molten globule nature of the protein could account for the presence of the different axial coordination of the heme iron. Such findings are meaningful with respect to the physiology of cytochrome c as electron transfer protein and as promoter of apoptosis.

  17. [Noradrenaline and cerebral aging].

    PubMed

    Jouvet, M; Albarede, J L; Lubin, S; Meyrignac, C

    1991-01-01

    The central functions of norepinephrine (NE) are a recent discovery: regulation of alertness and of the wakefulness-sleep cycle, maintenance of attention, memory and learning, cerebral plasticity and neuro-protection. The anatomical, histological, biochemical and physiological properties of the central noradrenergic system: extreme capacity for ramification and arborization; slow conduction, non-myelinized axons with extrasynaptic varicosities producing and releasing NE; frequency of co-transmission phenomena, and; neuromodulation with fiber effect responsible for improvement in the signal over background noise ratio and selection of significant stimuli form a true interface between the outside world and the central nervous system, notably for the neocortex in the context of the cognitive treatment of information. This central noradrenergic system is involved in the neurophysiology and the clinical features of cerebral aging (ideation-motor and cognitive function slowing down, loss of behavioral adjustment), neuro-degenerative disorders (SDAT, Parkinson's disease), certain aspects of depression and less obvious conditions (head injuries, sequelae of cerebrovascular accidents, sub-cortical dementia). The recent development of medications improving alertness (adrafinil, modafinil) with a pure central action and specifically noradrenergic, may contribute to an improvement in these multifactorial disorders.

  18. Cerebral cartography and connectomics

    PubMed Central

    Sporns, Olaf

    2015-01-01

    Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics. PMID:25823870

  19. Cerebral cartography and connectomics.

    PubMed

    Sporns, Olaf

    2015-05-19

    Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  20. Monitoring of cerebral autoregulation.

    PubMed

    Czosnyka, Marek; Miller, Chad

    2014-12-01

    Pressure autoregulation is an important hemodynamic mechanism that protects the brain against inappropriate fluctuations in cerebral blood flow in the face of changing cerebral perfusion pressure (CPP). Static autoregulation represents how far cerebrovascular resistance changes when CPP varies, and dynamic autoregulation represents how fast these changes happen. Both have been monitored in the setting of neurocritical care to aid prognostication and contribute to individualizing CPP targets in patients. Failure of autoregulation is associated with a worse outcome in various acute neurological diseases. Several studies have used transcranial Doppler ultrasound, intracranial pressure (ICP with vascular reactivity as surrogate measure of autoregulation), and near-infrared spectroscopy to continuously monitor the impact of spontaneous fluctuations in CPP on cerebrovascular physiology and to calculate derived variables of autoregulatory efficiency. Many patients who undergo such monitoring demonstrate a range of CPP in which autoregulatory efficiency is optimal. Management of patients at or near this optimal level of CPP is associated with better outcomes in traumatic brain injury. Many of these studies have utilized the concept of the pressure reactivity index, a correlation coefficient between ICP and mean arterial pressure. While further studies are needed, these data suggest that monitoring of autoregulation could aid prognostication and may help identify optimal CPP levels in individual patients.

  1. Delayed cerebral radiation necrosis.

    PubMed

    Morris, J G; Grattan-Smith, P; Panegyres, P K; O'Neill, P; Soo, Y S; Langlands, A O

    1994-02-01

    The clinical features and long-term outcome of seven patients with delayed cerebral radiation necrosis (DCRN) are described. Radiotherapy had been given for pituitary tumour (1), astrocytoma (2), pinealoma (2), craniopharyngioma (1) and parotid carcinoma (1). The mean latency to onset of the first neurological symptoms was 22 months (range 6-40 months), and mean duration of follow-up was 86 months (range 60-126). Three patients died at a mean of 84 months after radiotherapy (range 62-98). A fourth patient probably died from metastatic disease. Three patients remain alive, albeit severely disabled, after 5-10 years. The illness typically ran a stepwise course, with fits and stroke-like episodes occurring against a background of progressive dementia and somnolence. CT and MRI scans showed progressive ventricular dilatation associated with cerebral atrophy and diffuse or focal changes in the white matter. Four patients had had two or more neurosurgical procedures after the radiotherapy. In only one of the seven patients was the diagnosis made at presentation. DCRN produces a distinctive clinical picture, yet remains a poorly recognized complication of cranial irradiation.

  2. Etiology of cerebral palsy.

    PubMed

    Meberg, Alf; Broch, Harald

    2004-01-01

    To register the prevalence of cerebral palsy (CP) and determine etiological factors for the condition. Population based study with registration of CP-cases in children born during the 30-year period 1970-99. Cases with postneonatal etiology were excluded. 166 CP-cases were registered among 70 824 children, a prevalence of 2.3 per 1000 live born infants. The prevalence did not change significantly during the period. 66 (40%) were low birthweight infants (LBWIs; <2500 g), and 100 (60%) normal birthweight infants (NBWIs; > or = 2500 g). The origin was classified as prenatal in 37 (22%), perinatal/neonatal in 78 (47%) and unclassifiable in 51 (31 %). In LBWIs 39/66 (59%) had a perinatal/neonatal etiology, most frequently intra- or periventricular hemorrhages (IVH/PVH) and/or periventricular leukomalacia (PVL) or cerebral infarctions (CI) (17; 44%). In NBWIs 39/100 (39%) had a perinatal etiology, most frequently hypoxic-ischemic encephalopathy (HIE) (31; 79%). In a substantial percentage of CP-cases perinatal/neonatal brain injury was classified as the cause. Among these IVH/PVH/PVL/CI dominated in LBWIs, while HIE dominated in NBWIs. Our data may point to preventability of a larger part of CP than earlier suggested.

  3. Cerebral hyperperfusion syndrome.

    PubMed

    van Mook, Walther N K A; Rennenberg, Roger J M W; Schurink, Geert Willem; van Oostenbrugge, Robert Jan; Mess, Werner H; Hofman, Paul A M; de Leeuw, Peter W

    2005-12-01

    Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy is characterised by ipsilateral headache, hypertension, seizures, and focal neurological deficits. If not treated properly it can result in severe brain oedema, intracerebral or subarachnoid haemorrhage, and death. Knowledge of CHS among physicians is limited. Most studies report incidences of CHS of 0-3% after carotid endarterectomy. CHS is most common in patients with increases of more than 100% in perfusion compared with baseline after carotid endarterectomy and is rare in patients with increases in perfusion less than 100% compared with baseline. The most important risk factors in CHS are diminished cerebrovascular reserve, postoperative hypertension, and hyperperfusion lasting more than several hours after carotid endarterectomy. Impaired autoregulation as a result of endothelial dysfunction mediated by generation of free oxygen radicals is implicated in the pathogenesis of CHS. Treatment strategies are directed towards regulation of blood pressure and limitation of rises in cerebral perfusion. Complete recovery happens in mild cases, but disability and death can occur in more severe cases. More information about CHS and early institution of adequate treatment are of paramount importance in order to prevent these potentially severe complications.

  4. [Cerebral amyloid angiopathy].

    PubMed

    Sakai, Kenji; Yamada, Masahito

    2014-07-01

    Cerebral amyloid angiopathy (CAA) is a disorder characterized by the accumulation of amyloid proteins in the small and medium-sized blood vessels of the leptomeninges and central nervous system. Amyloid β protein (Aβ), immunoglobulin light chains, cystatin C, prion protein (PrP), ABri/ADan, transthyretin, and gelsoline, are all associated with CAA. While most CAA patients demonstrated sporadic Aβ-type amyloid deposition, a small number of patients present with familial forms, e.g. Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D), Icelandic-type HCHWA (HCHWA-I), familial British dementia (FBD), familial Danish dementia (FDD), and PrP-CAA. Deposited amyloid proteins damage smooth muscle cells in blood vessel walls leading to pathological appearances calling 'double-barreled' changes, fibrinoid necrosis, and microaneurysms. These structural abnormalities result in microinfarcts and hemorrhages in the central nervous system. Recurrent hemorrhage is a common clinical manifestation in patients with CAA; however, small multiple infarctions, progressive dementia, transient neurological symptoms, and CAA-related inflammation can also occur. The pathomechanisms of CAA remain unknown. Although improvements in imaging techniques have allowed us to identify patients with CAA more readily, pathological examination is still essential for a definite diagnosis. There have been no curative treatments for CAA so far.

  5. Reversible cerebral vasoconstriction syndrome.

    PubMed

    Calic, Z; Cappelen-Smith, C; Zagami, A S

    2015-06-01

    Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical-radiological syndrome characterised by severe thunderclap headaches with or without other neurological symptoms and multifocal constriction of cerebral arteries that usually resolves spontaneously within 3 months. Most patients recover completely, but up to 10% have a permanent neurological disability and some even die. Previously RCVS has been described in many clinical contexts and under different names with the term RCVS first being suggested in 2007 to unify the group. The condition may be spontaneous, but in up to 60% of cases it is secondary to another cause, including vasoactive substances (medications and illicit drugs), blood products and the post-partum state. It is believed to have a similar pathophysiological mechanism to the posterior reversible encephalopathy syndrome (PRES), and both can occur in similar clinical contexts and are frequently associated. Treatment options include calcium channel antagonists. RCVS occurs in a broad range of clinical situations making it an increasingly recognised condition about which doctors in various specialties need to be aware. © 2014 Royal Australasian College of Physicians.

  6. Cerebral Gluconeogenesis and Diseases

    PubMed Central

    Yip, James; Geng, Xiaokun; Shen, Jiamei; Ding, Yuchuan

    2017-01-01

    The gluconeogenesis pathway, which has been known to normally present in the liver, kidney, intestine, or muscle, has four irreversible steps catalyzed by the enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase. Studies have also demonstrated evidence that gluconeogenesis exists in brain astrocytes but no convincing data have yet been found in neurons. Astrocytes exhibit significant 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 activity, a key mechanism for regulating glycolysis and gluconeogenesis. Astrocytes are unique in that they use glycolysis to produce lactate, which is then shuttled into neurons and used as gluconeogenic precursors for reduction. This gluconeogenesis pathway found in astrocytes is becoming more recognized as an important alternative glucose source for neurons, specifically in ischemic stroke and brain tumor. Further studies are needed to discover how the gluconeogenesis pathway is controlled in the brain, which may lead to the development of therapeutic targets to control energy levels and cellular survival in ischemic stroke patients, or inhibit gluconeogenesis in brain tumors to promote malignant cell death and tumor regression. While there are extensive studies on the mechanisms of cerebral glycolysis in ischemic stroke and brain tumors, studies on cerebral gluconeogenesis are limited. Here, we review studies done to date regarding gluconeogenesis to evaluate whether this metabolic pathway is beneficial or detrimental to the brain under these pathological conditions. PMID:28101056

  7. Mitochondrial gene cytochrome b developmental and environmental expression in Aedes aegypti.

    USDA-ARS?s Scientific Manuscript database

    Cytochrome b, coded by mitochondrial DNA, is one of the cytochromes involved in electron transport in the respiratory chain of mitochondria. Cytochrome b is a critical intermediate in a mitochondrial death pathway. To reveal whether cytochrome b of the mosquito Aedes aegypti L. (AeaCytB) is developm...

  8. Microelectrochemistry and Measurement of the Diffusivity of Oxidized and Reduced Horse Heart Cytochrome c

    DTIC Science & Technology

    1989-10-01

    outer-sphere redox components and cytochrome c have been studied extensively. 4 However, cytochrome c is a solution protein where cytochrome c oxidase and...ferrocytochrome c to cytochrome c oxidase . This study profiles the diffusion of species over 1.4 lm to 26 4m and the characteristic collection

  9. Cerebral vascular hamartoma in a geriatric cat

    PubMed Central

    Martin-Vaquero, Paula; Moore, Sarah A; Wolk, Kendra E; Oglesbee, Michael J

    2014-01-01

    An 11-year-old castrated male domestic medium hair cat was presented with neurological signs consistent with a right thalamocortical lesion. Computed tomography (CT) images revealed a heterogeneously, hyperattenuating, poorly contrast enhancing intra-axial mass within the right lateral ventricle. The histological diagnosis at post-mortem examination was vascular hamartoma with hemorrhage and necrosis. This is the first report of a vascular hamartoma affecting the thalamocortex in a geriatric cat. Also, this is the first time that CT images of a feline cerebral vascular hamartoma have been reported. PMID:21277244

  10. Three-dimensional In Vivo Quantification of Knee Kinematics in Cerebral Palsy

    PubMed Central

    Seisler, Andrea R.; Alter, Katharine E.

    2008-01-01

    Cerebral palsy is the most common disabling condition in childhood, involving a diverse group of movement and posture disorders of varying etiologies. Yet, much is unknown about how cerebral palsy affects individual joints because currently applied techniques cannot quantify the three-dimensional kinematic parameters at the joint level. We quantified the effects of cerebral palsy at the knee using fast phase contrast MRI, with the ultimate intent of improving the assessment of joint impairments associated with cerebral palsy, improving clinical outcomes, and reducing the impact of cerebral palsy on function. We addressed three questions: (1) Can patients with cerebral palsy perform the required repetitive extension task? (2) Which of the 12 degrees of freedom defining complete knee kinematics are abnormal in individual patients with cerebral palsy and is the patellar tendon moment arm abnormal in these patients? (3) Are the individual kinematic differences consistent with clinical observations? All patients were able to perform the required task. We found kinematic differences for each patient with cerebral palsy consistent with clinical findings, in comparison to an able-bodied population. Fast phase contrast MRI may allow differentiation of patellofemoral and tibiofemoral function in various functional subtypes of cerebral palsy, providing insights into its management. PMID:18196431

  11. Effects of ketamine on isoflurane- and sevoflurane-induced cerebral vasodilation in rabbits.

    PubMed

    Nagase, Kiyoshi; Iida, Hiroki; Dohi, Shuji

    2003-04-01

    Although ketamine has been reported to have little effect on the cerebral circulation when used with other anesthetics, its effect on the cerebral vascular response to volatile anesthetics, which increase cerebral blood flow in a concentration-dependent manner, remains obscure. A closed cranial window was prepared in 15 pentobarbital-anesthetized adult rabbits. The cerebral pial arteriolar alteration induced by either isoflurane (n = 8) or sevoflurane (n = 7) at 0 (before volatile anesthetic), 0.33, 0.67, and 1.0 minimum alveolar concentration (MAC) was measured under three consecutive conditions: intravenous infusion with saline, with ketamine, and with ketamine plus l-arginine. Ketamine reduced the vasodilation induced by 0.67 (120 +/- 9% versus 113 +/- 9%; P <.05) and 1.0 MAC isoflurane (136 +/- 11% versus 118 +/- 10%; P <.05), but l-arginine did not restore the isoflurane-induced cerebral vasodilation. In rabbits inhaling sevoflurane, the degree of cerebral vasodilator response was smaller than that by isoflurane, and the cerebral vasodilation was comparable whether in the presence or absence of ketamine (with or without l-arginine). In conclusion, ketamine reduces isoflurane-induced cerebral vasodilation, apparently independently of nitric oxide formation, while sevoflurane-induced cerebral vasodilation is not significantly affected by ketamine.

  12. Flower colour and cytochromes P450†

    PubMed Central

    Tanaka, Yoshikazu; Brugliera, Filippa

    2013-01-01

    Cytochromes P450 play important roles in biosynthesis of flavonoids and their coloured class of compounds, anthocyanins, both of which are major floral pigments. The number of hydroxyl groups on the B-ring of anthocyanidins (the chromophores and precursors of anthocyanins) impact the anthocyanin colour, the more the bluer. The hydroxylation pattern is determined by two cytochromes P450, flavonoid 3′-hydroxylase (F3′H) and flavonoid 3′,5′-hydroxylase (F3′5′H) and thus they play a crucial role in the determination of flower colour. F3′H and F3′5′H mostly belong to CYP75B and CYP75A, respectively, except for the F3′5′Hs in Compositae that were derived from gene duplication of CYP75B and neofunctionalization. Roses and carnations lack blue/violet flower colours owing to the deficiency of F3′5′H and therefore lack the B-ring-trihydroxylated anthocyanins based upon delphinidin. Successful redirection of the anthocyanin biosynthesis pathway to delphinidin was achieved by expressing F3′5′H coding regions resulting in carnations and roses with novel blue hues that have been commercialized. Suppression of F3′5′H and F3′H in delphinidin-producing plants reduced the number of hydroxyl groups on the anthocyanidin B-ring resulting in the production of monohydroxylated anthocyanins based on pelargonidin with a shift in flower colour to orange/red. Pelargonidin biosynthesis is enhanced by additional expression of a dihydroflavonol 4-reductase that can use the monohydroxylated dihydrokaempferol (the pelargonidin precursor). Flavone synthase II (FNSII)-catalysing flavone biosynthesis from flavanones is also a P450 (CYP93B) and contributes to flower colour, because flavones act as co-pigments to anthocyanins and can cause blueing and darkening of colour. However, transgenic plants expression of a FNSII gene yielded paler flowers owing to a reduction of anthocyanins because flavanones are precursors of anthocyanins and flavones. PMID:23297355

  13. Interactions of Avocado (Persea americana) Cytochrome P-450 with Monoterpenoids

    PubMed Central

    Hallahan, David L.; Nugent, Jonathan H. A.; Hallahan, Beverly J.; Dawson, Glenn W.; Smiley, Diane W.; West, Jevon M.; Wallsgrove, Roger M.

    1992-01-01

    The microsomal fraction of avocado (Persea americana) mesocarp is a rich source of cytochrome P-450 active in the demethylation of xenobiotics. Cytochrome P-450 from this tissue has been purified and well characterized at the molecular level (DP O'Keefe, KJ Leto [1989] Plant Physiol 89: 1141-1149; KR Bozak, H Yu, R Sirevag, RE Christoffersen [1990] Proc Natl Acad Sci USA 87: 3904-3908). Despite this extensive characterization, the role of the enzyme in vivo was not established. Optical and electron paramagnetic resonance binding studies described here suggest that the monoterpenoids, nerol and geraniol, are substrates of avocado cytochrome P-450 (spectral dissociation constant of 7.2 and 35 micromolar, respectively). Avocado microsomes have been shown to catalyze the hydroxylation of these monoterpenoids, and both nerol and geraniol have been shown to inhibit the activity of avocado cytochrome P-450 toward the artificial substrate 7-ethoxycoumarin, with nerol a competitive inhibitor of this activity. PMID:16668790

  14. Genetics Home Reference: cytochrome P450 oxidoreductase deficiency

    MedlinePlus

    ... hormones, which are needed for normal development and reproduction. The hormonal changes associated with cytochrome P450 oxidoreductase ... which are essential for normal sexual development and reproduction; corticosteroids, which are involved in the body's response ...

  15. Rearrangement Reactions Catalyzed by Cytochrome P450s

    PubMed Central

    Ortiz de Montellano, Paul R.; Nelson, Sidney D.

    2010-01-01

    Cytochrome P450s promote a variety of rearrangement reactions both as a consequence of the nature of the radical and other intermediates generated during catalysis, and of the neighboring structures in the substrate that can interact either with the initial radical intermediates or with further downstream products of the reactions. This article will review several kinds of previously published cytochrome P450-catalyzed rearrangement reactions, including changes in stereochemistry, radical clock reactions, allylic rearrangements, “NIH” and related shifts, ring contractions and expansions, and cyclizations that result from neighboring group interactions. Although most of these reactions can be carried out by many members of the cytochrome P450 superfamily, some have only been observed with select P450s, including some reactions that are catalyzed by specific endoperoxidases and cytochrome P450s found in plants. PMID:20971058

  16. Electron transfer between multihaem cytochromes c₃ from Desulfovibrio africanus.

    PubMed

    Quintas, Pedro O; Oliveira, Márcia S; Catarino, Teresa; Turner, David L

    2013-04-01

    The tetrahaem type I cytochromes c3 from Desulfovibrionaceae shuttle electrons from a periplasmic hydrogenase to transmembrane electron transfer complexes. In D. africanus, it is believed that the electrons are received by another tetrahaem cytochrome c3, denoted type II, which is associated with the membrane complex. Thermodynamic measurements show that the type I cytochrome c3 has the potential to transfer two electrons at a time. This study uses two-dimensional NMR to investigate the exchange of electrons between type I and type II cytochromes c3 at equilibrium in intermediate stages of oxidation. The results indicate that the two proteins are physiological partners but that only single-electron transfers occur in solution. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Activation of Oxygen by Cytochrome P-450 and Other Haemoproteins

    NASA Astrophysics Data System (ADS)

    Metelitsa, D. I.

    1982-11-01

    Data on the activation of molecular oxygen by the full microsomal hydroxylating system containing cytochrome P-450 as the terminal oxygenase are examined. The nature of the hydroxylating agent, which is the oxenoid Fe3+O, is analysed. The autoxidation reactions of cytochrome P-450 from various sources, haemoglobin, myoglobin, and peroxidases are compared and the role of the axial ligands of the haem iron and the structure of the active centres of the haemoproteins in this process is demonstrated. The possible mechanisms of the oxidation of organic compounds by peroxides with participation of cytochrome P-450, cytochrome c, haemoglobin, and catalase are examined critically. Haemoproteins have been divided into three groups in terms of the type of peroxide oxidation reactions. The relative contributions of the radical and two-electron reactions in the oxidation of compounds by peroxides with participation of different haemoproteins are analysed. The bibliography includes 184 references.

  18. Pediatric traumatic carotid, vertebral and cerebral artery dissections: a review.

    PubMed

    Mortazavi, Martin M; Verma, Ketan; Tubbs, R Shane; Harrigan, Mark

    2011-12-01

    Traumatic cerebral dissections are rare but potentially dangerous conditions that through improved diagnostics have recently gained increased interest. However, there is still a significant lack of knowledge on the natural history, as well as on the best treatment options. Most of the literature on this topic consists of case reports and retrospective studies with no prospective randomized controlled studies. In our review, we highlight the fact that there is no level 1 evidence for the natural history of cerebral dissections or for the best treatment. We present 26 case studies derived from 70 pediatric patients affected by dissections, occlusions, and pseudoaneurysms.

  19. [Ultrastructural changes in the cerebral cortex following transcranial micropolarization].

    PubMed

    Akimova, I M; Novikova, T A

    1978-12-01

    Electron microscopy of the cerebral cortex in cats and monkeys following transcranial micropolarization (TCMP) demonstrated ultrastructural changes whose degree was dependent on the electric current intensity and the stimulation period. In the focus of stimulation the current affected the brain tissue directly, different elements of the cerebral cortex showing unegual sensitivity to various TCMP regimens. The glia was the first to respond, then the neuronal bodies, and the last -- the synaptic structures. In the areas distant from the TCMP focus synaptic components altered first. The ultrastructural changes revealed were not of pathological character.

  20. Inventory control: cytochrome c oxidase assembly regulates mitochondrial translation.

    PubMed

    Mick, David U; Fox, Thomas D; Rehling, Peter

    2011-01-01

    Mitochondria maintain genome and translation machinery to synthesize a small subset of subunits of the oxidative phosphorylation system. To build up functional enzymes, these organellar gene products must assemble with imported subunits that are encoded in the nucleus. New findings on the early steps of cytochrome c oxidase assembly reveal how the mitochondrial translation of its core component, cytochrome c oxidase subunit 1 (Cox1), is directly coupled to the assembly of this respiratory complex.

  1. Characterization of Cytochrome 579, an Unusual Cytochrome Isolated from an Iron-Oxidizing Microbial Community▿

    PubMed Central

    Singer, Steven W.; Chan, Clara S.; Zemla, Adam; VerBerkmoes, Nathan C.; Hwang, Mona; Hettich, Robert L.; Banfield, Jillian F.; Thelen, Michael P.

    2008-01-01

    A novel, soluble cytochrome with an unusual visible spectral signature at 579 nm (Cyt579) has been characterized after isolation from several different microbial biofilms collected in an extremely acidic ecosystem. Previous proteogenomic studies of an Fe(II)-oxidizing community indicated that this abundant red cytochrome could be extracted from the biofilms with dilute sulfuric acid. Here, we found that the Fe(II)-dependent reduction of Cyt579 was thermodynamically favorable at a pH of >3, raising the possibility that Cyt579 acts as an accessory protein for electron transfer. The results of transmission electron microscopy of immunogold-labeled biofilm indicated that Cyt579 is localized near the bacterial cell surface, consistent with periplasmic localization. The results of further protein analysis of Cyt579, using preparative chromatofocusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, revealed three forms of the protein that correspond to different N-terminal truncations of the amino acid sequence. The results of intact-protein analysis corroborated the posttranslational modifications of these forms and identified a genomically uncharacterized Cyt579 variant. Homology modeling was used to predict the overall cytochrome structure and heme binding site; the positions of nine amino acid substitutions found in three Cyt579 variants all map to the surface of the protein and away from the heme group. Based on this detailed characterization of Cyt579, we propose that Cyt579 acts as an electron transfer protein, shuttling electrons derived from Fe(II) oxidation to support critical metabolic functions in the acidophilic microbial community. PMID:18469132

  2. Cytochrome c3 from the sulfate-reducing anaerobe Desulfovibrio africanus Benghazi: antigenic properties.

    PubMed Central

    Singleton, R; Denis, J; Campbell, L L

    1982-01-01

    Antisera were prepared against cytochromes c3 from Desulfovibrio africanus, D. vulgaris, and D. salexigens. Cross-reactions were observed between antisera to D. vulgaris and D. africanus cytochromes and heterologous cytochromes c3. A weak cross-reaction with antisera against both D. vulgaris and D. africanus cytochromes and the acid form of the D. salexigens cytochrome was seen; the basic form did not react. Images PMID:6181052

  3. XC_0531 encodes a c-type cytochrome biogenesis protein and is required for pathogenesis in Xanthomonas campestris pv. campestris.

    PubMed

    Chen, Lei; Wang, Mingpeng; Huang, Li; Zhang, Zhaojie; Liu, Fanghua; Lu, Guangtao

    2017-06-27

    The phytopathogenic Xanthomonas campestris pv.campestris is a gram-negative bacterium and the causal agent of black-rot disease of cruciferous crops. Many gram-negative bacteria possess a family of proteins, called Dsbs, which are involved in disulfide bond formation in certain periplasmic proteins. In our preliminary screening of the virulence to the plants we identified that gene XC_0531 which annotated gene dsbD of Xanthomonas campestris pv. campestris (Xcc) is related to the virulence to the host plants. Here, we found XC_0531 encoded a DsbD like protein. Its deletion is sensitive to DTT and copper, decreased accumulation of free thiols in periplasm. Its deletion also affected heme synthesis, position of Soret band and the production of peak c550. This suggests that XC_0531 is related to c-type cytochromes biogenesis. XC_0531 mutation decreased the utilization of different carbon sources (such as galactose, xylose, maltose, saccharose and glucose), reduced extracellular polysaccharide (EPS) production, decreased extracellular enzyme activities (protease, cellulose and amylase), slowed down growth rate of Xcc and weakened virulence to the plants. These results suggest that these phenotypes caused by XC_0531 mutation is possibly due to deficient biosynthesis of c-type cytochromes in respiration chain and the formation of disulfide bonds. Our work confirmed the function of XC_0531 and provide theory basis for scientists working on molecular mechanisms of cytochrome c biogenesis, pathogenesis of Xcc, development of EPS commercial values and protecting plant from black rot. We confirmed the function of gene XC_0531, which encodes a DsbD like protein, a protein correlated with c-type cytochrome biogenesis. This gene is related to the virulence to plants by affecting funtion of cytochromes c and probably disulfide bonds modification of proteins in type II secretion system (T2SS).

  4. Cytochrome P450 expression in oesophageal cancer.

    PubMed Central

    Murray, G I; Shaw, D; Weaver, R J; McKay, J A; Ewen, S W; Melvin, W T; Burke, M D

    1994-01-01

    The cytochrome P450 superfamily of enzymes play a central part in the metabolism of carcinogens and anti-cancer drugs. The expression, cellular localisation, and distribution of different forms of P450 and the functionally associated enzymes epoxide hydrolase and glutathione S-transferases have been investigated in oesophageal cancer and non-neoplastic oesophageal tissue using immunohistochemistry. Expression of the different enzymes was confined to epithelial cells in both non-neoplastic samples and tumour samples except the CYP3A was also identified in mast cells and glutathione S-transferase pi was present in chronic inflammatory cells. CYP1A was present in a small percentage of non-neoplastic samples but both CYP2C and CYP3A were absent. Epoxide hydrolase was present in half of the non-neoplastic samples and the different classes of glutathione S-transferase were present in a low number of samples. In carcinomas CYP1A, CYP3A, epoxide hydrolase, and glutathione S-transferase pi were expressed in at least 60% of samples. The expression of glutathione S-transferases alpha and mu were significantly less in adenocarcinoma compared with squamous carcinoma. Images Figure 1 Figure 2 Figure 3 PMID:8200549

  5. Keeping the spotlight on cytochrome P450.

    PubMed

    Shalan, Hadil; Kato, Mallory; Cheruzel, Lionel

    2017-06-06

    This review describes the recent advances utilizing photosensitizers and visible light to harness the synthetic potential of P450 enzymes. The structures of the photosensitizers investigated to date are first presented along with their photophysical and redox properties. Functional photosensitizers range from organic and inorganic complexes to nanomaterials as well as the biological photosystem I complex. The focus is then on the three distinct approaches that have emerged for the activation of P450 enzymes. The first approach utilizes the in situ generation of reactive oxygen species entering the P450 mechanism via the peroxide shunt pathway. The other two approaches are sustained by electron injections into catalytically competent heme domains either facilitated by redox partners or through direct heme domain reduction. Achievements as well as pitfalls of each approach are briefly summarized. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone. Copyright © 2017. Published by Elsevier B.V.

  6. Cytochrome C stabilization and immobilization in aerogels.

    PubMed

    Harper-Leatherman, Amanda S; Wallace, Jean Marie; Rolison, Debra R

    2011-01-01

    Sol-gel-derived aerogels are three-dimensional, nanoscale materials that combine large surface areas and high porosities. These traits make them useful for any rate-critical chemical process, particularly sensing or electrochemical applications, once physical or chemical moieties are incorporated into the gels to add their functionality into the ultraporous scaffold. Incorporating biomolecules into aerogels has been challenging due to the inability of most biomolecules to remain structurally intact within the gels during the necessary supercritical fluid processing. However, the heme protein cytochrome c (cyt. c) forms self-organized superstructures around gold (or silver) nanoparticles in buffer that can be encapsulated within silica and processed to form aerogels in which cyt. c retains its characteristic visible absorption. The gold (or silver) nanoparticle-nucleated superstructures protect the majority of the protein from the harsh physicochemical conditions necessary to form an aerogel. The Au∼cyt. c superstructures exhibit rapid gas-phase recognition of nitric oxide (NO) within the aerogel matrix, as facilitated by the high-quality pore structure of the aerogel, and remain viable for weeks at room temperature.

  7. Evolutionary origin of mitochondrial cytochrome P450.

    PubMed

    Omura, Tsuneo; Gotoh, Osamu

    2017-05-01

    Different molecular species of cytochrome P450 (P450) are distributed between endoplasmic reticulum (microsomes) and mitochondria in animal cells. Plants and fungi have many microsomal P450s, but no mitochondrial P450 has so far been reported. To elucidate the evolutionary origin of mitochondrial P450s in animal cells, available evidence is examined, and the virtual absence of mitochondrial P450 in plants and fungi is confirmed. It is also suggested that a microsomal P450 is the ancestor of animal mitochondrial P450s. It is likely that the endoplasmic reticulum-targeting sequence at the amino-terminus of a microsomal P450 was converted to a mitochondria-targeting sequence possibly by point mutations of a few amino acid residues or by an exon-shuffling/moving event shortly after animal lineage diverged from plants and fungi in the course of evolution of eukaryotes. It is suggested that the microsome-type P450 first imported into mitochondria utilized the existing ferredoxin in the matrix to receive electrons from NADPH, retained its oxygenase activity in the mitochondria, and gradually diversified to several P450s with different substrate specificities in the course of the evolution of animals. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  8. Novel extrahepatic cytochrome P450s

    SciTech Connect

    Karlgren, Maria . E-mail: Maria.Karlgren@imm.ki.se; Miura, Shin-ichi; Ingelman-Sundberg, Magnus

    2005-09-01

    The cytochrome P450 enzymes are highly expressed in the liver and are involved in the metabolism of xenobiotics. Because of the initiatives associated with the Human Genome Project, a great progress has recently been seen in the identification and characterization of novel extrahepatic P450s, including CYP2S1, CYP2R1, CYP2U1 and CYP2W1. Like the hepatic enzymes, these P450s may play a role in the tissue-specific metabolism of foreign compounds, but they may also have important endogenous functions. CYP2S1 has been shown to metabolize all-trans retinoic acid and CYP2R1 is a major vitamin D 25-hydroxylase. Regarding their metabolism of xenobiotics, much remains to be established, but CYP2S1 metabolizes naphthalene and it is likely that these P450s are responsible for metabolic activation of several different kinds of xenobiotic chemicals and contribute to extrahepatic toxicity and carcinogenesis.

  9. Modular assembly of yeast cytochrome oxidase.

    PubMed

    McStay, Gavin P; Su, Chen Hsien; Tzagoloff, Alexander

    2013-02-01

    Previous studies of yeast cytochrome oxidase (COX) biogenesis identified Cox1p, one of the three mitochondrially encoded core subunits, in two high-molecular weight complexes combined with regulatory/assembly factors essential for expression of this subunit. In the present study we use pulse-chase labeling experiments in conjunction with isolated mitochondria to identify new Cox1p intermediates and place them in an ordered pathway. Our results indicate that before its assimilation into COX, Cox1p transitions through five intermediates that are differentiated by their compositions of accessory factors and of two of the eight imported subunits. We propose a model of COX biogenesis in which Cox1p and the two other mitochondrial gene products, Cox2p and Cox3p, constitute independent assembly modules, each with its own complement of subunits. Unlike their bacterial counterparts, which are composed only of the individual core subunits, the final sequence in which the mitochondrial modules associate to form the holoenzyme may have been conserved during evolution.

  10. Purification of cytochrome c oxidase by lysine-affinity chromatography.

    PubMed

    Felsch, J; Kotake, S; Copeland, R A

    1992-02-01

    A method for the purification of cytochrome c oxidase that is based on the affinity of this enzyme for polycations such as poly-L-lysine is described. When detergent extracts of bovine cardiac mitochondria were applied to either a poly-L-lysine-agarose or a lysine-Sepharose column at low ionic strength, cytochrome c oxidase was found to adhere tightly, whereas the bulk of the proteins were eluted by washing with the same buffer. The cytochrome c oxidase was eluted by application of a linear potassium chloride gradient to the columns. The resulting enzyme was identical to that obtained by more traditional purification methods in terms of its subunit composition, optical and resonance Raman spectra, and cytochrome c oxidizing activity. When detergent extracts of spheroplasts from Paracoccus denitrificans were applied to these columns, the cytochrome c oxidase from this organism was also found to adhere tightly. Thus this purification method appears applicable to both prokaryotic and eukaryotic forms of the enzyme. The advantages of this new purification method are that it is less labor intensive than the traditional procedure and less expensive than methods based on cytochrome c-affinity chromatography.

  11. Methionine ligand lability of homologous monoheme cytochromes c.

    PubMed

    Levin, Benjamin D; Walsh, Kelly A; Sullivan, Kristal K; Bren, Kara L; Elliott, Sean J

    2015-01-05

    Direct electrochemical analysis of adsorbed bacterial monoheme cytochromes c has revealed a phenomenological loss of the axial methionine when examined using pyrolytic "edge-plane" graphite (EPG) electrodes. While prior findings have reported that the Met-loss state may be quantitatively understood using the cytochrome c from Hydrogenobacter thermophilus as a model system, here we demonstrate that the formation of the Met-loss state upon EPG electrodes can be observed for a range of cytochrome orthologs. Through an electrochemical comparison of the wild-type proteins from organisms of varying growth temperature optima, we establish that Met-ligand losses at graphite surfaces have similar energetics to the "foldons" for known protein folding pathways. Furthermore, a downward shift in reduction potential to approximately -100 mV vs standard hydrogen electrode was observed, similar to that of the alkaline transition found in mitochondrial cytochromes c. Pourbaix diagrams for the Met-loss forms of each cytochrome, considered here in comparison to mutants where the Met-ligand has been substituted to His or Ala, suggest that the nature of the Met-loss state is distinct from either a His-/aquo- or a bis-His-ligated heme center, yet more closely matches the pKa values found for bis-His-ligated hemes., We find the propensity for adoption of the Met-loss state in bacterial monoheme cytochromes c scales with their overall thermal stability, though not with the specific stability of the Fe-Met bond.

  12. Insights into the Role of Substrates on the Interaction between Cytochrome b5 and Cytochrome P450 2B4 by NMR

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Le Clair, Stéphanie V.; Huang, Rui; Ahuja, Shivani; Im, Sang-Choul; Waskell, Lucy; Ramamoorthy, Ayyalusamy

    2015-02-01

    Mammalian cytochrome b5 (cyt b5) is a membrane-bound protein capable of donating an electron to cytochrome P450 (P450) in the P450 catalytic cycle. The interaction between cyt b5 and P450 has been reported to be affected by the substrates of P450; however, the mechanism of substrate modulation on the cyt b5-P450 complex formation is still unknown. In this study, the complexes between full-length rabbit cyt b5 and full-length substrate-free/substrate-bound cytochrome P450 2B4 (CYP2B4) are investigated using NMR techniques. Our findings reveal that the population of complexes is ionic strength dependent, implying the importance of electrostatic interactions in the complex formation process. The observation that the cyt b5-substrate-bound CYP2B4 complex shows a weaker dependence on ionic strength than the cyt b5-substrate-free CYP2B4 complex suggests the presence of a larger fraction of steoreospecific complexes when CYP2B4 is substrate-bound. These results suggest that a CYP2B4 substrate likely promotes specific interactions between cyt b5 and CYP2B4. Residues D65, V66, T70, D71 and A72 are found to be involved in specific interactions between the two proteins due to their weak response to ionic strength change. These findings provide insights into the mechanism underlying substrate modulation on the cyt b5-P450 complexation process.

  13. Exercise increases mitochondrial glutamate oxidation in the mouse cerebral cortex.

    PubMed

    Herbst, Eric A F; Holloway, Graham P

    2016-07-01

    The present study investigated the impact of acute exercise on stimulating mitochondrial respiratory function in mouse cerebral cortex. Where pyruvate-stimulated respiration was not affected by acute exercise, glutamate respiration was enhanced following the exercise bout. Additional assessment revealed that this affect was dependent on the presence of malate and did not occur when substituting glutamine for glutamate. As such, our results suggest that glutamate oxidation is enhanced with acute exercise through activation of the malate-aspartate shuttle.

  14. Diffuse Cerebral Language Representation in Tuberous Sclerosis Complex

    PubMed Central

    Gallagher, Anne; Tanaka, Naoaki; Suzuki, Nao; Liu, Hesheng; Thiele, Elizabeth A.; Stufflebeam, Steven M.

    2012-01-01

    Introduction Tuberous sclerosis complex (TSC) is a multisystem genetic disorder affecting multiple organs, including the brain, and very often associated with epileptic activity. Language acquisition and development seems to be altered in a significant proportion of patients with TSC. In the present study, we used magnetoencephalography (MEG) to investigate spatiotemporal cerebral language processing in subjects with TSC and epilepsy during a reading semantic decision task, compared to healthy control participants. Methods Fifteen patients with TSC and 31 healthy subjects performed a lexico-semantic decision task during MEG recording. Minimum-norm estimates (MNE) were computed allowing identification of cerebral generators of language evoked fields (EF) in each subject. Results Source analysis of the language EF demonstrated early bilateral medial occipital activation (125ms) followed by a fusiform gyrus activation around 135ms. At 270ms post stimuli presentation, a strong cerebral activation was recorded in the left basal temporal language area. Finally, cerebral activations were measured in Wernicke’s area followed by Broca’s area. The healthy control group showed larger and earlier language activations in Broca and Wernicke’s areas compared to TSC patients. Moreover, cerebral activation from Broca’s area was greater than activation from Wernicke’s area in both groups, but this difference between anterior and posterior regions was smaller in the TSC group. Finally, the activation latency difference between Broca and Wernicke’s areas was greater in healthy controls than in TSC patients, which shows that activations in these areas are more serial in control subjects compared to TSC patients in whom activations occur more simultaneously. Conclusions This is the first study to investigate cerebral language pattern in patients with TSC. Compared to healthy controls, atypical neuromagnetic language responses may reflect cerebral reorganization in these

  15. Coordination effects on the electronic structure of the CuA site of cytochrome c oxidase

    NASA Astrophysics Data System (ADS)

    Koizumi, Kenichi; Shigeta, Yasuteru; Okuyama, Orio; Nakamura, Haruki; Takano, Yu

    2012-04-01

    The CuA site is the electron mediator in cytochrome c oxidase (CcO), providing an appropriate electronic structure for rapid electron transfer. We have studied the coordinating effects of His, Met, and the peptide carbonyl group of Glu of the CuA site, using the density functional theory. Our computation demonstrates that the His ligation provides strong orbital and electrostatic effects on the electronic structure of the CuA site, while that the Met coordination gives weak orbital and electrostatic effects. A coordination of the peptide carbonyl group affects the electronic structure of the CuA site only electrostatically.

  16. Cerebral Arterial Fenestrations

    PubMed Central

    Cooke, Daniel L; Stout, Charles E; Kim, Warren T; Kansagra, Akash P; Yu, John Paul; Gu, Amy; Jewell, Nicholas P; Hetts, Steven W; Higashida, Randall T; Dowd, Christopher F; Halbach, Van V

    2014-01-01

    Summary Arterial fenestrations are an anatomic variant with indeterminate significance. Given the controversy surrounding fenestrations we sought their prevalence within our practice along with their association with other cerebrovascular anomalies. We retrospectively reviewed 10,927 patients undergoing digital subtraction angiography between 1992 and 2011. Dictated reports were searched for the terms “fenestration” or “fenestrated” with images reviewed for relevance, yielding 228 unique cases. A Medline database search from February 1964 to January 2013 generated 304 citations, 127 cases of which were selected for analysis. Cerebral arterial fenestrations were identified in 228 patients (2.1%). At least one aneurysm was noted in 60.5% of patients, with an aneurysm arising from the fenestration in 19.6% of patients. Aneurysmal subarachnoid hemorrhage or non-aneurysmal subarachnoid hemorrhage were present in 60.1% and 15.8%, respectively. For the subset of patients with an aneurysm arising directly from a fenestration relative to those patients with an aneurysm not immediately associated with a fenestration, the prevalence of aneurysmal subarachnoid hemorrhage was 66.7% vs. 58.6% (p = 0.58). Fenestrations were more often within the posterior circulation (73.2%) than the anterior circulation (24.6%), though there was no difference in the prevalence of aneurysms within these groups (61.1% vs. 60.7%, p = 1.0). Cerebral arterial fenestrations are an anatomic variant more often manifesting at the anterior communicating arterial complex and basilar artery and with no definite pathological relationship with aneurysms. PMID:24976087

  17. Reversible cerebral shrinkage in kwashiorkor: an MRI study.

    PubMed

    Gunston, G D; Burkimsher, D; Malan, H; Sive, A A

    1992-08-01

    Protein energy malnutrition is associated with cerebral atrophy which may be detrimental to intellectual development. The aim of this study was to document the anatomical abnormalities which lead to the appearance of cerebral atrophy using magnetic resonance imaging (MRI) in the acute stage of kwashiorkor and to monitor changes during nutritional rehabilitation. Twelve children aged 6 to 37 months requiring admission to hospital for the treatment of kwashiorkor were studied. The children were evaluated clinically, biochemically, and by MRI of their brains on admission and 30 and 90 days later. Brain shrinkage was present in every child on admission. White and grey matter appeared equally affected and the myelination was normal for age. At 90 days, the cerebral changes had resolved in nine and improved substantially in the remainder, by which time serum proteins and weight for age were within the normal range. The findings of this study suggest that brain shrinkage associated with kwashiorkor reverses rapidly with nutritional rehabilitation.

  18. Effect of calcium ions on electron transfer between hemes a and a(3) in cytochrome c oxidase.

    PubMed

    Vygodina, T V; Dyuba, A V; Konstantinov, A A

    2012-08-01

    Kinetics of the reduction of the hemes in cytochrome c oxidase in the presence of high concentration of ruthenium(III)hexaammine chloride was examined using a stopped-flow spectrophotometer. Upon mixing of the oxidized enzyme with dithionite and Ru(NH(3))(6)(3+), three well-resolved phases were observed: heme a reduction reaching completion within a few milliseconds is followed by two slow phases of heme a(3) reduction. The difference spectrum of heme a(3) reduction in the visible region is characterized by a maximum at ~612 nm, rather than at 603 nm as was believed earlier. It is shown that in the case of bovine heart cytochrome c oxidase containing a special cation-binding site in which reversible binding of calcium ion occurs, heme a(3) reduction is slowed down by low concentrations of Ca(2+). The effect is absent in the case of the bacterial cytochrome oxidase in which the cation-binding site contains a tightly bound Ca(2+) ion. The data corroborate the inhibition of the cytochrome oxidase enzymatic activity by Ca(2+) ions discovered earlier and indicate that the cation affects intramolecular electron transfer.

  19. Ca/sup 2 +/ transport against its electrochemical gradient in cytochrome oxidase vesicles reconstituted with mitochondrial hydrophobic proteins

    SciTech Connect

    Rosier, R.N.; Tucker, D.A.; Meerdink, S.; Jain, I.; Gunter, T.E.

    1981-09-01

    Control experiments verified that the energization conditions used produced appropriately oriented membrane potentials. Partially purified hydrophobic mitochondria protein complexes were found to be less effective than complex V. The reconstituted system showed cation selectivity since Ca/sup 2 +/, Mn/sup 2 +/, and Rb/sup +/ were transported, while Na/sup +/ was not. Low levels of uncoupler, which did not affect oxidation rates, were found to partially inhibit Ca/sup 2 +/ uptake regardless of the membrane potential polarity. Uncoupling levels of uncoupler markedly inhibited Ca/sup 2 +/ uptake in internally negative cytochrome oxidase vesicles; however, inhibition in internally positive cytochrome oxidase vesicles was less relative to that at lower levels of uncoupler. The uncoupling combination of nigericin, valinomycin, and K/sup +/ was inhibitory to uptake regardless of membrane potential polarity. A reconstituted system of oxidative phosphorylation, which contains a hydrophobic protein fraction, energized with cytochrome oxidase similarly accumulated Ca/sup 2 +/ despite formation of an internally positive membrane potential. The results suggest that cytochrome oxidase, when coupled to appropriate hydrophobic mitochondrial proteins, can act as an electrogenic Ca/sup 2 +/ pump deriving its energy directly from electron transport. (JMT)

  20. Electron transfer properties and catalytic competence of cytochrome b5 in the fusion protein Hmwb5-EGFP in reactions catalyzed by cytochrome P450 3A4.

    PubMed

    Yantsevich, A V; Gilep, A A; Usanov, S A

    2009-08-01

    In the present paper we describe studies on molecular mechanisms of protein-protein interactions between cytochrome P450 3A4 (CYP3A4) and cytochrome b(5), the latter being incorporated into the artificial recombinant protein Hmwb(5)-EGFP containing full-length cytochrome b(5) (functional module) and a mutant form of the green fluorescent protein EGFP (signal module) fused into a single polypeptide chain. It is shown that cytochrome b(5) within the fusion protein Hmwb(5)-EGFP can be reduced by NADPH-cytochrome P450 reductase in the presence of NADPH, the rate of reduction being dependent on solution ionic strength, indicating that the signal module does not prevent the interaction of the flavo- and hemeproteins. Interaction of cytochrome P450 3A4 and Hmwb(5)-EGFP was estimated based on spin equilibrium shift of cytochrome P450 3A4 to high-spin state in the presence of Hmwb(5)-EGFP, as well as based on steady-state fluorescence anisotropy of the EGFP component of the fusion protein in the presence of CYP3A4. The engineering of chimeric protein Hmwb(5)-EGFP gives an independent method to determine dissociation constant for the complex of cytochrome P450 and cytochrome b(5) that is less sensitive to environmental factors compared to spectrophotometric titration used before. Reconstitution of catalytic activity of cytochrome P450 3A4 in the reaction of testosterone 6beta-hydroxylation in the presence of Hmwb(5)-EGFP indicates that cytochrome b(5) in the fusion protein is able to stimulate the hydroxylation reaction. Using other fusion proteins containing either cytochrome b(5) or its hydrophilic domain to reconstitute catalytic activity of cytochrome P450 3A4 showed that the hydrophobic domain of cytochrome b(5) participates not only in hemeprotein interaction, but also in electron transfer from cytochrome b(5) to cytochrome P450.

  1. Attenuation by methyl mercury and mercuric sulfide of pentobarbital induced hypnotic tolerance in mice through inhibition of ATPase activities and nitric oxide production in cerebral cortex.

    PubMed

    Chuu, Jiunn-Jye; Huang, Zih-Ning; Yu, Hsun-Hsin; Chang, Liang-Hao; Lin-Shiau, Shoei-Yn

    2008-06-01

    This study is aimed at exploring the possible mechanism of hypnosis-enhancing effect of HgS or cinnabar (a traditional Chinese medicine containing more than 95% HgS) in mice treated with pentobarbital. We also examined whether the effect of HgS is different from that of the well-known methyl mercury (MeHg). After a short period (7 days) of oral administration to mice, a nontoxic dose (0.1 g/kg) of HgS not only significantly enhanced pentobarbital-induced hypnosis but also attenuated tolerance induction; while a higher dose (1 g/kg) of HgS or cinnabar exerted an almost irreversible enhancing effect on pentobarbital-hypnosis similar to that of MeHg (2 mg/kg) tested, which was still effective even after 10 or 35 days cessation of administration. To study comparatively the effects of different mercury forms from oral administration of MeHg and HgS on membrane ATPase activities of experimental mice, analysis of the Hg content in the cerebral cortex revealed that correlated with the decrease of Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities. Furthermore, NO levels of blood but not that of cerebral cortex were also decreased by mercuric compounds. Although pentobarbital alone enhanced cytochrome p450-2C9 in time dependent manner, all of mercurial compounds tested had no such effect. All of these findings indicated that the mercurial compounds including cinnabar, HgS and MeHg exert a long-lasting enhancing hypnotic activity without affecting pentobarbital metabolism, which provides evidence-based sedative effect of cinnabar used in Chinese traditional medicine for more than 2,000 years. The nontoxic HgS dosing (0.1 g/kg/day) for consecutive 7 days is perhaps useful for delaying or preventing pentobarbital-tolerance.

  2. Cerebral Small Vessel Disease and Chronic Kidney Disease

    PubMed Central

    2015-01-01

    Chronic kidney disease, defined by a decreased glomerular filtration rate or albuminuria, is recognized as a major global health burden, mainly because it is an established risk factor for cardiovascular and cerebrovascular diseases. The magnitude of the effect of chronic kidney disease on incident stroke seems to be higher in persons of Asian ethnicity. Since the kidney and brain share unique susceptibilities to vascular injury due to similar anatomical and functional features of small artery diseases, kidney impairment can be predictive of the presence and severity of cerebral small vessel diseases. Chronic kidney disease has been reported to be associated with silent brain infarcts, cerebral white matter lesions, and cerebral microbleeds, independently of vascular risk factors. In addition, chronic kidney disease affects cognitive function, partly via the high prevalence of cerebral small vessel diseases. Retinal artery disease also has an independent relationship with chronic kidney disease and cognitive impairment. Stroke experts are no longer allowed to be ignorant of chronic kidney disease. Close liaison between neurologists and nephrologists can improve the management of cerebral small vessel diseases in kidney patients. PMID:25692105

  3. Selective arterial distribution of cerebral hyperperfusion in Fabry disease.

    PubMed

    Moore, D F; Herscovitch, P; Schiffmann, R

    2001-07-01

    Fabry disease is an X-linked recessive deficiency of lysosomal alpha-galactosidase A associated with an increased risk of early onset cerebrovascular disease. The disorder is reported to affect the posterior circulation predominantly. This hypothesis was investigated directly by the measurement of regional cerebral blood flow with positron emission tomography (PET). Resting regional cerebral blood flow (rCBF) in 26 hemizygous patients with Fabry disease and 10 control participants was examined using H(2)15O and PET. Statistical parametric mapping (SPM(t), SPM99) and PET images of patients and controls were produced. Significantly increased SPM(t) clusters were then color coded and blended with a coregistered T1 magnetic resonance imaging (MRI) template. Cerebral arterial territory maps were digitized and rescaled. Custom OpenGL and ImageVision Library C++ code was written to allow a first-order affine transformation of the blended SPM(t) and MRI template onto the arterial territory map. The affine transformation was constrained by choosing corresponding cerebral landmark "tie points" between the SPM(t) [symbol: see text] MRI template images and the cerebral arterial territory maps. The data demonstrated that the posterior circulation is the predominant arterial territory with a significantly increased rCBF in Fabry disease. No arterial distribution had a decreased rCBF.

  4. Streptococcus agalactiae impairs cerebral bioenergetics in experimentally infected silver catfish.

    PubMed

    Baldissera, Matheus D; Souza, Carine F; Parmeggiani, Belisa S; Santos, Roberto C V; Leipnitz, Guilhian; Moreira, Karen L S; da Rocha, Maria Izabel U M; da Veiga, Marcelo L; Baldisserotto, Bernardo

    2017-10-01

    It is becoming evident that bacterial infectious diseases affect brain energy metabolism, where alterations of enzymatic complexes of the mitochondrial respiratory chain and creatine kinase (CK) lead to an impairment of cerebral bioenergetics which contribute to disease pathogenesis in the central nervous system (CNS). Based on this evidence, the aim of this study was to evaluate whether alterations in the activity of complex IV of the respiratory chain and CK contribute to impairment of cerebral bioenergetics during Streptococcus agalactiae infection in silver catfish (Rhamdia quelen). The activity of complex IV of the respiratory chain in brain increased, while the CK activity decreased in infected animals compared to uninfected animals. Brain histopathology revealed inflammatory demyelination, gliosis of the brain and intercellular edema in infected animals. Based on this evidence, S. agalactiae infection causes an impairment in cerebral bioenergetics through the augmentation of complex IV activity, which may be considered an adaptive response to maintain proper functioning of the electron respiratory chain, as well as to ensure ongoing electron flow through the electron transport chain. Moreover, inhibition of cerebral CK activity contributes to lower availability of ATP, contributing to impairment of cerebral energy homeostasis. In summary, these alterations contribute to disease pathogenesis linked to the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Time-resolved magnetic circular dichroism spectroscopy of photolyzed carbonmonoxy cytochrome c oxidase (cytochrome aa3).

    PubMed

    Goldbeck, R A; Dawes, T D; Einarsdóttir, O; Woodruff, W H; Kliger, D S

    1991-07-01

    Nanosecond time-resolved magnetic circular dichroism (TRMCD) and time-resolved natural circular dichroism (TRCD) measurements of photolysis products of the CO complex of eukaryotic cytochrome c oxidase (CcO-CO) are presented. TRMCD spectra obtained at 100 ns and 10 microseconds after photolysis are diagnostic of pentacoordinate cytochrome a3Fe2+, as would be expected for simple photodissociation. Other time-resolved spectroscopies (UV-visible and resonance Raman), however, show evidence for unusual Fea3(2+) coordination after CO photolysis (Woodruff, W. H., O. Einarsdóttir, R. B. Dyer, K. A. Bagley, G. Palmer, S. J. Atherton, R. A. Goldbeck, T. D. Dawes, and D. S. Kliger. 1991. Proc. Nat. Acad. Sci. U.S.A. 88:2588-2592). Furthermore, time-resolved IR experiments have shown that photodissociated CO binds to CuB+ prior to recombining with Fea3(2+) (Dyer, R. B., O. Einarsdóttir, P. M. Killough, J. J. López-Garriga, and W. H. Woodruff. 1989. J. Am. Chem. Soc. 111:7657-7659). A model of the CcO-CO photolysis cycle which is consistent with all of the spectroscopic results is presented. A novel feature of this model is the coordination of a ligand endogenous to the protein to the Fe axial site vacated by the photolyzed CO and the simultaneous breaking of the Fe-imidazole(histidine) bond.

  6. Caspase cleavage of cytochrome c1 disrupts mitochondrial function and enhances cytochrome c release.

    PubMed

    Zhu, Yushan; Li, Min; Wang, Xiaohui; Jin, Haijing; Liu, Shusen; Xu, Jianxin; Chen, Quan

    2012-01-01

    Mitochondrial catastrophe can be the cause or consequence of apoptosis and is associated with a number of pathophysiological conditions. The exact relationship between mitochondrial catastrophe and caspase activation is not completely understood. Here we addressed the underlying mechanism, explaining how activated caspase could feedback to attack mitochondria to amplify further cytochrome c (cyto.c) release. We discovered that cytochrome c1 (cyto.c1) in the bc1 complex of the mitochondrial respiration chain was a novel substrate of caspase 3 (casp.3). We found that cyto.c1 was cleaved at the site of D106, which is critical for binding with cyto.c, following apoptotic stresses or targeted expression of casp.3 into the mitochondrial intermembrane space. We demonstrated that this cleavage was closely linked with further cyto.c release and mitochondrial catastrophe. These mitochondrial events could be effectively blocked by expressing non-cleavable cyto.c1 (D106A) or by caspase inhibitor z-VAD-fmk. Our results demonstrate that the cleavage of cyto.c1 represents a critical step for the feedback amplification of cyto.c release by caspases and subsequent mitochondrial catastrophe.

  7. Identification of a Small Tetraheme Cytochrome c and a Flavocytochrome c as Two of the Principal Soluble Cytochromes c in Shewanella oneidensis Strain MR1

    PubMed Central

    Tsapin, A. I.; Vandenberghe, I.; Nealson, K. H.; Scott, J. H.; Meyer, T. E.; Cusanovich, M. A.; Harada, E.; Kaizu, T.; Akutsu, H.; Leys, D.; Van Beeumen, J. J.

    2001-01-01

    Two abundant, low-redox-potential cytochromes c were purified from the facultative anaerobe Shewanella oneidensis strain MR1 grown anaerobically with fumarate. The small cytochrome was completely sequenced, and the genes coding for both proteins were cloned and sequenced. The small cytochrome c contains 91 residues and four heme binding sites. It is most similar to the cytochromes c from Shewanella frigidimarina (formerly Shewanella putrefaciens) NCIMB400 and the unclassified bacterial strain H1R (64 and 55% identity, respectively). The amount of the small tetraheme cytochrome is regulated by anaerobiosis, but not by fumarate. The larger of the two low-potential cytochromes contains tetraheme and flavin domains and is regulated by anaerobiosis and by fumarate and thus most nearly corresponds to the flavocytochrome c-fumarate reductase previously characterized from S. frigidimarina to which it is 59% identical. However, the genetic context of the cytochrome genes is not the same for the two Shewanella species, and they are not located in multicistronic operons. The small cytochrome c and the cytochrome domain of the flavocytochrome c are also homologous, showing 34% identity. Structural comparison shows that the Shewanella tetraheme cytochromes are not related to the Desulfovibrio cytochromes c3 but define a new folding motif for small multiheme cytochromes c. PMID:11425747

  8. Identification of a small tetraheme cytochrome c and a flavocytochrome c as two of the principal soluble cytochromes c in Shewanella oneidensis strain MR1

    NASA Technical Reports Server (NTRS)

    Tsapin, A. I.; Vandenberghe, I.; Nealson, K. H.; Scott, J. H.; Meyer, T. E.; Cusanovich, M. A.; Harada, E.; Kaizu, T.; Akutsu, H.; Leys, D.; Van Beeumen, J. J.

    2001-01-01

    Two abundant, low-redox-potential cytochromes c were purified from the facultative anaerobe Shewanella oneidensis strain MR1 grown anaerobically with fumarate. The small cytochrome was completely sequenced, and the genes coding for both proteins were cloned and sequenced. The small cytochrome c contains 91 residues and four heme binding sites. It is most similar to the cytochromes c from Shewanella frigidimarina (formerly Shewanella putrefaciens) NCIMB400 and the unclassified bacterial strain H1R (64 and 55% identity, respectively). The amount of the small tetraheme cytochrome is regulated by anaerobiosis, but not by fumarate. The larger of the two low-potential cytochromes contains tetraheme and flavin domains and is regulated by anaerobiosis and by fumarate and thus most nearly corresponds to the flavocytochrome c-fumarate reductase previously characterized from S. frigidimarina to which it is 59% identical. However, the genetic context of the cytochrome genes is not the same for the two Shewanella species, and they are not located in multicistronic operons. The small cytochrome c and the cytochrome domain of the flavocytochrome c are also homologous, showing 34% identity. Structural comparison shows that the Shewanella tetraheme cytochromes are not related to the Desulfovibrio cytochromes c(3) but define a new folding motif for small multiheme cytochromes c.

  9. Identification of a small tetraheme cytochrome c and a flavocytochrome c as two of the principal soluble cytochromes c in Shewanella oneidensis strain MR1

    NASA Technical Reports Server (NTRS)

    Tsapin, A. I.; Vandenberghe, I.; Nealson, K. H.; Scott, J. H.; Meyer, T. E.; Cusanovich, M. A.; Harada, E.; Kaizu, T.; Akutsu, H.; Leys, D.; hide

    2001-01-01

    Two abundant, low-redox-potential cytochromes c were purified from the facultative anaerobe Shewanella oneidensis strain MR1 grown anaerobically with fumarate. The small cytochrome was completely sequenced, and the genes coding for both proteins were cloned and sequenced. The small cytochrome c contains 91 residues and four heme binding sites. It is most similar to the cytochromes c from Shewanella frigidimarina (formerly Shewanella putrefaciens) NCIMB400 and the unclassified bacterial strain H1R (64 and 55% identity, respectively). The amount of the small tetraheme cytochrome is regulated by anaerobiosis, but not by fumarate. The larger of the two low-potential cytochromes contains tetraheme and flavin domains and is regulated by anaerobiosis and by fumarate and thus most nearly corresponds to the flavocytochrome c-fumarate reductase previously characterized from S. frigidimarina to which it is 59% identical. However, the genetic context of the cytochrome genes is not the same for the two Shewanella species, and they are not located in multicistronic operons. The small cytochrome c and the cytochrome domain of the flavocytochrome c are also homologous, showing 34% identity. Structural comparison shows that the Shewanella tetraheme cytochromes are not related to the Desulfovibrio cytochromes c(3) but define a new folding motif for small multiheme cytochromes c.

  10. Molecular organization of cytochrome c2 near the binding domain of cytochrome bc1 studied by electron spin-lattice relaxation enhancement.

    PubMed

    Pietras, Rafał; Sarewicz, Marcin; Osyczka, Artur

    2014-06-19

    Measurements of specific interactions between proteins are challenging. In redox systems, interactions involve surfaces near the attachment sites of cofactors engaged in interprotein electron transfer (ET). Here we analyzed binding of cytochrome c2 to cytochrome bc1 by measuring paramagnetic relaxation enhancement (PRE) of spin label (SL) attached to cytochrome c2. PRE was exclusively induced by the iron atom of heme c1 of cytochrome bc1, which guaranteed that only the configurations with SL to heme c1 distances up to ∼30 Å were detected. Changes in PRE were used to qualitatively and quantitatively characterize the binding. Our data suggest that at low ionic strength and under an excess of cytochrome c2 over cytochrome bc1, several cytochrome c2 molecules gather near the binding domain forming a "cloud" of molecules. When the cytochrome bc1 concentration increases, the cloud disperses to populate additional available binding domains. An increase in ionic strength weakens the attractive forces and the average distance between cytochrome c2 and cytochrome bc1 increases. The spatial arrangement of the protein complex at various ionic strengths is different. Above 150 mM NaCl the lifetime of the complexes becomes so short that they are undetectable. All together the results indicate that cytochrome c2 molecules, over the range of salt concentration encompassing physiological ionic strength, do not form stable, long-lived complexes but rather constantly collide with the surface of cytochrome bc1 and ET takes place coincidentally with one of these collisions.

  11. Long-term therapy with cytochrome c, flavin mononucleotide and thiamine diphosphate for a patient with Kearns-Sayre syndrome.

    PubMed

    Nakagawa, E; Osari, S; Yamanouchi, H; Matsuda, H; Goto, Y; Nonaka, I

    1996-01-01

    Cardiocrome, containing cytochrome c, flavin mononucleotide and thiamine diphosphate, was administered intravenously for 22 months to a patient with Kearns-Sayre syndrome. This combined therapy alleviated the patient's easy fatigability, motor disability, corneal edema and chilblains, but was not effective for his ophthalmoplegia, blepharoptosis or hearing loss. Truncal ataxia, dysphagia and an atrioventricular block appeared even with this therapy. Although the abnormal distribution of cerebral blood flow demonstrated by single photon emission computed tomography was improved, serial cranial magnetic resonance imaging and electrophysiological examination revealed progressive changes. In conclusion, this therapy was favorably effective for impaired skeletal muscle function and corneal edema, but not for ocular movements, central nervous system symptoms or cardiac conduction abnormalities, because irreversible degeneration had probably occurred in these organs.

  12. Risk Factors for Cerebral Venous Thrombosis.

    PubMed

    Silvis, Suzanne M; Middeldorp, Saskia; Zuurbier, Susanna M; Cannegieter, Suzanne C; Coutinho, Jonathan M

    2016-09-01

    Cerebral venous thrombosis (CVT) is a rare thrombotic disorder involving the cerebral veins and dural sinuses. In contrast to more common sites of venous thromboembolism (VTE), such as the legs and lungs, CVT mainly affects young adults and children, and women are affected three times more often than men. Although presenting symptoms are variable, headache is usually the first symptom, often in combination with focal neurologic deficits and epileptic seizures. The primary therapy for CVT consists of heparin followed by oral anticoagulation for at least 3 to 6 months. The mortality in the acute phase is 5 to 10% and a substantial proportion of survivors suffer from long-term disabilities. A large number of risk factors have been linked to CVT, although the scientific evidence for an association varies considerably between risk factors. Some risk factors, such as hereditary thrombophilia, correspond with risk factors for more common sites of VTE, whereas others, such as head trauma, are specific to CVT. In most patients, at least one risk factor can be identified. In this review, we provide an overview of the risk factors for CVT.

  13. Analysis of the changes in the oxidation of brain tissue cytochrome-c-oxidase in traumatic brain injury patients during hypercapnoea: a broadband NIRS study.

    PubMed

    Tachtsidis, Ilias; Tisdall, Martin M; Pritchard, Caroline; Leung, Terence S; Ghosh, Arnab; Elwell, Clare E