Successful management of refractory intracranial hypertension from acute hyperammonemic encephalopathy in a woman with ornithine transcarbamylase deficiency.

BACKGROUND: Ornithine transcarbamylase deficiency (OTCD) is the most common of the urea cycle disorders and results in an accumulation of ammonia and its metabolites. Excess ammonia in the brain is metabolized to glutamine, which increases intracellular osmolarity and contributes to cytotoxic edema. METHODS: We report a case of a woman heterozygous for OTCD who developed acute hyperammonemic encephalopathy and increased intracranial pressure (ICP). RESULTS: Despite hemodialysis, protein restriction, and administration of pharmacologic nitrogen scavengers, she developed progressive cerebral edema and increased ICP that was refractory to maximal medical management. She underwent a bifrontal decompressive craniectomy resulting in resolution of her intracranial hypertension. CONCLUSION: Aggressive multimodality management of the patient coupled with bifrontal decompressive hemicraniectomy was a life-saving measure, offering the patient a reasonable outcome. At 6 month follow-up she had moderate disability on the Glasgow Outcome Score associated with cognitive difficulties.

Feasibility study of organic matter and Ammonium removal using loofa sponge as a supporting medium in an aerated submerged fixed-film reactor (ASFFR)

Biofilm systems are efficient in the removal of organic matter and ammonium from wastewaters. In this study, loofa sponge, a natural product, was used as a supporting medium in an aerated submerged fixed-film reactor to evaluate its performance in removing organic matter and nitrogen from wastewater. Four pilot runs were performed with chemical oxygen demand (COD) concentrations of 100, 200, 300 and 400 mg l-1 to provide an organic loading rate of 0.6, 1.2, 1.8, and 2.4 kg m-3d-1 respectively. In these pilot runs, the influent ammonium nitrogen concentrations were justified to 5, 10, 15 and 20 mg l-1 as N to provide an influent nitrogen loading of 30, 60, 90 and 120 g m-3.d-1 respectively. Although soluble COD removal efficiency greater than 80 percent was achieved up to a loading rate of 2.4 kg m-3d-1, loofa deformation and clogging after 72 days of application might be considered a serious shortcoming during use in full-scale applications. Nitrogen removal efficiency decreased from 85.6 percent at an organic loading rate of 0.6 kg m-3d-1 to 56.1 percent at an organic loading rate of 2.4 kg m-3d-1.

Nitrification Inhibitors from the root tissues of Brachiaria humidicola, a tropical grass.

Nitrification inhibitory activity was found in root tissue extracts of Brachiaria humidicola, a tropical pasture grass. Two active inhibitory compounds were isolated by activity-guided fractionation, using recombinant Nitrosomonas europaea containing luxAB genes derived from the bioluminescent marine gram-negative bacterium Vibrio harveyi. The compounds were identified as methyl-p-coumarate and methyl ferulate, respectively. Their nitrification inhibitory properties were confirmed in chemically synthesized preparations of each. The IC50 values of chemically synthesized preparations were 19.5 and 4.4 microM, respectively. The ethyl, propyl, and butyl esters of p-coumaric and ferulic acids inhibited nitrification, whereas the free acid forms did not show inhibitory activity.

Prenylated flavanones isolated from flowers of Azadirachta indica (the neem tree) as antimutagenic constituents against heterocyclic amines.

Four prenylated flavanones were isolated from the methanol extract of the flowers of Azadirachta indica (the neem tree) as potent antimutagens against Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole) in the Salmonella typhimurium TA98 assay by activity-guided fractionation. Spectroscopic properties revealed that those compounds were 5,7,4'-trihydroxy-8-prenylflavanone (1), 5,4'-dihydroxy-7-methoxy-8-prenylflavanone (2), 5,7,4'-trihydroxy-3',8-diprenylflavanone (3), and 5,7,4'-trihydroxy-3',5'-diprenylflavanone (4). All isolated compounds were found for the first time in this plant. The antimutagenic IC(50) values of compounds 1-4 were 2.7 +/- 0.1, 3.7 +/- 0.1, 11.1 +/- 0.1, and 18.6 +/- 0.1 microM in the preincubation mixture, respectively. These compounds also similarly inhibited the mutagenicity of Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine). All of the compounds 1-4 strongly inhibited ethoxyresorufin O-dealkylation activity of cytochrome P450 1A isoforms, which catalyze N-hydroxylation of heterocyclic amines. However, compounds 1-4 did not show significant inhibition against the direct-acting mutagen NaN(3). Thus, the antimutagenic effect of compounds 1-4 would be mainly based on the inhibition of the enzymatic activation of heterocyclic amines.

Some furfural derivatives as nitrification inhibitors.

Three series of furfural derivatives, namely N-O-furfural oxime ethers, furfural Schiff bases (furfurylidene anilines), and furfural chalcones, have been synthesized and evaluated for nitrification inhibition activity in laboratory incubation studies in typic Ustocrept soil. Furfural oxime ethers and furfural Schiff bases showed potential activity, but furfural chalcones were only mildly active. N-O-ethyl furfural oxime among the oxime ethers, and furfurylidine-4-chloroaniline among the furfural Schiff bases, performed the best. These two compounds showed more than 50% nitrification inhibition on the 45th day at 5% dose as compared to 73% inhibition by nitrapyrin. Activity of furfural oxime ethers decreased with an increase in carbon atoms in the N-O-alkyl side chain. Introduction of a chlorine atom in the phenyl ring of furfurylidene anilines increased the persistence of their activity. N-O-Ethyl furfural oxime and furfurylidine-4-chloroaniline coated urea performed at par with their application in solution form. Ethyl and N-O-isopropyl oxime, as well as chloro- and nitro- substituted Schiff bases, did not reveal any phytotoxicity (adverse effect on germination) on chickpea seeds (Cicer arietinum) even at the highest dose (40 ppm, soil basis).

Anti- and pro-oxidative properties of PADMA 28, a Tibetan herbal formulation.

There is growing public interest in traditional medicine. PADMA 28, a multicompound herbal preparation derived from Tibetan medicine, has proven efficacy in some clinical trials and tests at the cellular level. We report here on studies of PADMA 28 at the molecular level. Extracts of PADMA 28 contain both reducing and metal ion-chelating substances. In this way, PADMA 28 acts as a powerful antioxidant or prooxidant, depending on its concentration and the reaction under study.

Nitrification inhibitors from the roots of Leucaena leucocephala.

The nitrification inhibition (NI) bioassay guided fractionation of the methanol extract of lyophilized and milled roots of Leuceana leucocephala resulted in the isolation of four compounds, 1-4, as confirmed from their 1H and 13C NMR spectral data. Compound 1, gallocatechin, was the most active NI inhibitor at 12 microg/mL. Epigallocatechin, 2, and epicatechin, 4, isolated as mixtures, were not assayed individually for their NI inhibitory activities against the nitrification bacterium Nitrosomonas europaea.

Thyroxin and thiouracyl influence upon some biochemical parameters in chicken thymuses.

Administration of L-thyroxin in a dose of 30 micrograms/chicken, i.m. and 2-thiouracyl in a dose of 0.3 mg/chicken, i.m. for an interval of 3 days, determined, at the thymus level, increases of total protein content in the Tu group, in parallel with decreases of the nitrogen of free amino acids level in the Tx group, increases of DNA content in the Tx group and an increase of the thymus weight in both groups. Modifications are due to the action of thyroxin, on the one hand, and on the other to the doses of antithyroid drug which determines a raise of T4 content in the plasma and the manifestation of activities specific to this hormone.

[Changes in cardiac rhythm in humans during breathing compressed air under pressure up to 1.1 MPa (results of the rhythmo-cardiographic study)]. / Izmenenie serdechnogo ritma u cheloveka vo vremia dykhaniia szhatym vozdukhom pod davleniem do 1.1 MPa (rezul'taty ritmo-kardiograficheskogo issledovaniia).

Dynamics of cardiac rhythm has been considered according to rhythmocardiographic characteristics of heart rate under orthostatic test and one-stage step-test in four altitude chamber experiments where air under pressure of 0.4-1.1 MPa is used as a breathing mixture. It is shown that these characteristics linearly depend on the partial nitrogen and oxygen pressure and hyperbaric bradycardia essentially decreases in the final period of isopression due to toxic oxygen effect. Cytochrome C decreases hyperbaric bradycardia. Under hyperbaric conditions the regulation of cardiac rhythm proceeds with altered central vegetative effects provided a direct effect of higher nitrogen and oxygen pressure on the sinusal node cells.

Synthesis of isoindolo[2,1-a]quinoline derivatives and their effects on N2-induced hypoxia.

A variety of isoindolo[2,1-a]quinoline derivatives as well as the following related heterocycles have been prepared: 11b,12-dihydro-5H-isoindolo[2,1-b][2]benzazepine-7,13-dione (8a), 7,8,14,14a-tetrahydroisoindolo[2,1-c][3]benzazocine-5, 13-dione (8b), 6a,7-dihydroisoquinolino[2,3-a]quinoline-5,12-dione (12), 2,3,3a-4-tetrahydropyrrolo[1,2-a]quinoline-1,5-dione (14), and pyrido[2',3':3,4]pyrrolo[1,2-a]quinoline-5,11(5H)-dione (17). The key synthetic step involves an intramolecular Friedel-Crafts reaction of acid chlorides such as isoindole-1-acetyl chlorides (4), the acids (3) of which were prepared starting with 2-arylisoindole-1,3(2H)-diones (2-arylphthalimides) (1). The protective effects of isoindolo[2,1-a]quinoline derivatives (19 and 20) against N2-induced hypoxia were examined. Among them, 6-(diethylaminomethyl)isoindolo[2,1-a]quinoline-5,11(5H)-dio ne (19b) showed the most potency.

Cyanide and sulfide interact with nitrogenous compounds to influence the relaxation of various smooth muscles.

Sodium nitroprusside relaxed guinea pig ileum after the segment had been submaximally contracted by either histamine or acetylcholine, intact isolated rabbit gall bladder after submaximal contraction by either acetylcholine or cholecystokinin octapeptide, and rat pulmonary artery helical strips after submaximal contraction with norepinephrine. In each of these cases the relaxation produced by nitroprusside was at least partially reversed by the subsequent addition of excess sodium cyanide. Cyanide, however, in nontoxic concentrations did not reverse the spasmolytic effects of hydroxylamine hydrochloride, sodium azide, nitroglycerin, sodium nitrite, or nitric oxide hemoglobin on guinea pig ileum, nor did cyanide alone in the same concentrations have any effect. The similar interaction between nitroprusside and cyanide on rabbit aortic strips is not dependent on the presence of an intact endothelial cell layer. Also, on rabbit aortic strips and like cyanide, sodium sulfide reversed the spasmolytic effects of azide and hydroxylamine, but it had little or no effect on the relaxation induced by papaverine. Unlike cyanide, however, sulfide augmented the relaxation induced by nitroprusside, and it reversed the effects of nitric oxide hemoglobin, nitroglycerin, and nitrite. A direct chemical reaction between sulfide and nitroprusside may account for the difference between it and cyanide. Although evidence was obtained also for a direct chemical reaction between sulfide and norepinephrine, that reaction does not seem to have played a role in these results. These observations suggest the existence of at least three distinct subclasses of so-called nitric oxide vasodilators. At least in some cases cyanide and sulfide cannot be acting by the same mechanism in their modifications of the responses to the agonists.

Failure of naloxone or physostigmine to reverse nitrogen anesthesia in guinea pigs.

Stress as well as anesthesia has been reported to stimulate endorphin release. The possibility that the stress of compression at 1 atm/min or nitrogen anesthesia, or both, might release endorphins was tested in guinea pigs with the use of naloxone--a narcotic antagonist, and physostigmine--a cholinesterase inhibitor. The animals received i.p. equal volumes of either drugs or the placebo just before compression to 32 ATA (oxygen less than or equal to 1 ATA). The pressure at loss of righting reflex was compared. Nitrogen anesthesia occurred at mean pressures ranging from 26.9 to 27.8 ATA, with no statistical differences demonstrated in all groups. It is concluded that 1) neither naloxone nor physostigmine reversed nitrogen narcosis and 2) stress of compression or nitrogen narcosis, or both, failed to show effects attributable to increased endorphin release.

Nonlinear antagonism of anesthesia in mice by pressure.

Previous studies have shown a rectilinear antagonism by pressure of nitrous oxide or isoflurane anesthesia in mice (pressure reversal). Since a rectilinear pressure reversal is predicted by the critical volume hypothesis for anesthesia, we examined this phenomenon with two other gases. We measured the doses of argon or nitrogen which abolished the righting reflex in 50% of animals (ED50) at various high pressures produced by the addition of helium. The ED50 values of argon and nitrogen alone are 16.7 +/- 1.37 and 38.3 +/- 1.62 atmospheres absolute (ATA). Fifty-five percent more argon and 27% more nitrogen is needed to produce anesthesia at 100 ATA. However the increasing anesthetic requirements with pressure were curvilinearly related to pressure, rising most steeply at pressures near the ED50 without helium. This suggests that the pressure reversal of anesthesia is not simply a reciprocal anesthetic expansion-pressure compression phenomenon as predicted by the critical volume hypothesis. It suggests that anesthetics and pressure act at different sites.