WOR5, a Novel Tungsten-Containing Aldehyde Oxidoreductase from Pyrococcus furiosus with a Broad Substrate Specificity

WOR5 is the fifth and last member of the family of tungsten-containing oxidoreductases purified from the hyperthermophilic archaeon Pyrococcus furiosus. It is a homodimeric protein (subunit, 65 kDa) that contains one [4Fe-4S] cluster and one tungstobispterin cofactor per subunit. It has a broad substrate specificity with a high affinity for several substituted and nonsubstituted aliphatic and aromatic aldehydes with various chain lengths. The highest catalytic efficiency of WOR5 is found for the oxidation of hexanal (V(max) = 15.6 U/mg, K(m) = 0.18 mM at 60°C). Hexanal-incubated enzyme exhibits S = 1/2 electron paramagnetic resonance signals from [4Fe-4S](1+) (g values of 2.08, 1.93, and 1.87) and W(5+) (g values of 1.977, 1.906, and 1.855). Cyclic voltammetry of ferredoxin and WOR5 on an activated glassy carbon electrode shows a catalytic wave upon addition of hexanal, suggesting that ferredoxin can be a physiological redox partner. The combination of WOR5, formaldehyde oxidoreductase, and aldehyde oxidoreductase forms an efficient catalyst for the oxidation of a broad range of aldehydes in P. furiosus

Utilisation cérébrale du glucose dans la paralysie supranucléaire progressive et dans la dégénérescence strio-nigrique. Etude par scanner à positons.

Dix-huit études du métabolisme cérébral du glucose ont été réalisées chez des sujets atteints du syndrome "Parkinson Plus", au moyen de la tomographie par émission de positrons (TEP) et du traceur [18F]Fluorodeoxyglucose (FDG). Neuf patients étaient atteints de paralysie supranucléaire progressive. Chez 7 d'entre eux, il existait une distribution spécifique des altérations métaboliques, caractérisée par une atteinte prédominante du cortex frontal, alors que le métabolisme du glucose était diffusément diminué chez 1 sujet et normal dans 1 cas. Dans les 7 cas d'hypométabolisme frontal, les aires motrices et prémotrices étaient plus affectées que les zones paralimbiques et préfrontales. Bien que cette image métabolique soit typique de l'affection, aucune corrélation nette entre les anomalies métaboliques et les résultats des tests neuropsychologiques n'a pu être mise en évidence. Neuf études ont été effectuées chez 7 patients présentant un syndrome extrapyramidal évolutif, pharmacologiquement résistant, ayant conduit au diagnostic probable de dégénérescence nigrostriée. Un hypométabolisme hautement significatif (3 SD) a été démontré chez tous les sujets au niveau du putamen et du noyau caudé et, dans une moindre mesure, dans le cortex moteur/prémoteur et préfrontal. Les analyses en résonance magnétique ont mis en évidence la présence de dépôts ferriques anormaux dans le putamen, en l'absence d'anomalies corticales. Ces résultats suggèrent que la méthode TEP/FDG fournit un index de la fonction cérébrale résiduelle dans des zones en dégénérescence et permet de détecter les répercussions fonctionnelles à distance, résultant de déafférentation. Dans le cadre des syndromes parkinsoniens, les images obtenues au moyen de la TEP sont d'un intérêt diagnostique direct. La présence d'un hypométabolisme dans le striatum pourrait expliquer la résistance à la L-dopa et constituer un élément de mauvais pronostic

Sudden death after oxygen toxicity seizure during hyperbaric oxygen treatment: Case report

Acute cerebral oxygen toxicity (ACOT) is a known side effect of hyperbaric oxygen treatment (HBOT), which can cause generalised seizures. Fortunately, it has a low incidence and is rarely harmful. Nevertheless, we present a case of a 37 year-old patient with morbid obesity who died unexpectedly after an oxygen toxicity seizure in the hyperbaric chamber. Considering possible causes, physiologic changes in obesity and obesity hypoventilation syndrome may increase the risk of ACOT. Obesity, especially in extreme cases, may hinder emergency procedures, both in- and outside of a hyperbaric chamber. Physicians in the hyperbaric field should be aware of the possibility of a fatal outcome after ACOT through the described mechanisms and take appropriate preventative measures. Basic airway management skills are strongly advised for involved physicians, especially when specialised personnel and equipment are not immediately available

Brain glucose metabolism in postanoxic syndrome. Positron emission tomographic study.

Thirteen positron emission tomographic studies of cerebral glucose utilization were carried out in 12 patients with postanoxic syndrome due to cardiac arrest. Seven subjects were in a persistent vegetative state. The 5 other subjects were normally conscious, but disclosed focal neurological signs. When compared with normal values, mean cerebral glucose metabolism was drastically decreased (+/- 50%) in vegetative subjects, and to a lesser degree (+/- 25%) in conscious patients. The most consistent regional alterations were found in the parieto-occipital cortex (9 cases), the frontier between vertebral and carotid arterial territories, followed by the frontomesial junction (5 cases), the striatum (3 cases with dystonia), thalamus (2 cases), and visual cortex (2 cases with cortical blindness). These data suggest that brain anoxia can result in global brain hypometabolism, which appears related to the vigilance state, as well as in regional alterations preferentially located in arterial border zones

Brain glucose metabolism in postanoxic syndrome due to cardiac arrest

Using positron emission tomography (PET), thirteen studies of regional brain glucose utilization were performed in 12 patients with postanoxic syndrome due to cardiac arrest. Investigations were carried out at least one month after brain anoxia. Seven subjects were in a persistent vegetative state. The others had regained normal consciousness with various residual neurological signs. When compared with normal values obtained in 16 normal, age-matched subjects, mean cerebral glucose metabolism was drastically decreased (+/- 50%) in vegetative cases, and to a lesser degree (+/- 25%) in conscious subjects. The most consistent regional alterations were observed in the parieto-occipital cortex (9 cases), the frontier between vertebral and carotid arterial territories. Other selective anomalies were found in the frontomesial junction (5 cases), the striatum (3 cases with dystonia), and the visual cortex (2 cases with cortical blindness). This study suggests that cerebral anoxia results in a global brain hypometabolism, which appears related to the vigilance state, as well as in regional disturbances preferentially located in arterial border zones. Although our findings remain to be confirmed in larger series, they suggest that PET provides a useful index of residual brain tissue function after anoxia and may assist in the monitoring of postanoxic encephalopathies

Physostigmine results in an increased decrement in brain glucose consumption in Alzheimer's disease.

The responsibility of cerebral cholinergic lesions for the weak clinical response to cholinergic neurotransmission enhancement of Alzheimer's disease (AD) was studied by measuring the effects of physostigmine on glucose consumption and neuropsychological tests. Ten AD and ten aged normals (AN) were examined twice, under placebo and under maximal tolerated dose of physostigmine, in randomized order and blind fashion. Under physostigmine, both groups showed better performances in tests measuring attention (P < 0.05-0.001) but not long-term memory, and cerebral glucose consumption was regionally modified (P < 0.0001). We observed a regional decrease in AD and in AN which was larger in AD, where each patient exhibited a mean metabolic decrease. With normalized values, AD and AN showed a similar decrease in the metabolic values of prefrontal cortex and striatum (P = 0.0003). These findings suggest that cholinergic neurotransmission enhancement depresses glucose consumption and increases selective attention in similar ways in both groups, but to a larger extent in AD. This suggests that brain metabolism in AD over-responds to enhancement of cholinergic neurotransmission. The observed weak response of clinical symptomatology to anticholinesterase agents does not appear to be due to the failure to enhance the activity of the cholinergic system in AD