Hyperbaric oxygen ameliorates delayed neuropsychiatric syndrome of carbon monoxide poisoning.

OBJECTIVES: Delayed neuropsychiatric syndrome (DNS) is characterized by mental impairment, motor dysfunction, dementia, or psychosis that develops between a few days and weeks after acute carbon monoxide (CO) poisoning. One possible mechanism responsible for CO-mediated encephalopathy involves oxidative stress, such as lipid peroxidation, caused by the cellular uptake of CO and which leads to an inflammatory cascade. There is no current effective treatment for DNS. We applied 8-40 sessions of hyperbaric oxygen therapy (HBO2) to patients with DNS and evaluated its effectiveness. METHODS: After admission, all patients were administered piracetam or bromocriptine, or both, and received HBO2. Neuropsychiatric tests included EEG, mini-mental status examination (MMSE), brain MRI, event-related potential (ERP), and brain perfusion scan (brain SPECT). Results of these tests were compared before and after HBO2, and the clinical features were monitored during this period. RESULTS: The symptoms of DNS for all patients improved significantly after HBOT. Although white matter changes remained evident in the brain MRI scans, other examinations such as EEG, MMSE, ERP, and 99mTc-ECD brain SPECT were nearly normal after HBOT. CONCLUSION: Our results suggest that HBO2 decreases the severity of impairment in patients with DNS. Although a large randomized trial is required to address the efficacy of this therapy, therapeutic application of HBO2 may be recommended in patients with DNS after CO poisoning.

Regulation of a recombinant pea nuclear apyrase by calmodulin and casein kinase II.

A cDNA encoding a pea nuclear apyrase was previously cloned. Overexpressions of a full-length and a truncated cDNA have been successfully expressed in Escherichia coli BL21(DE3). The resulting fusion proteins, apyrase and the C-terminus (residues 315-453) of apyrase, were used for calmodulin (CaM) binding and phosphorylation studies. Fusion protein apyrase but not the C-terminus of apyrase can be recognized by polyclonal antibody pc480. This suggested that the motif recognized by pc480 was located in the N-terminal region of apyrase. The recombinant apyrase protein also showed an activity 70 times higher than that of endogenous apyrase using ATP as a substrate. The recombinant apyrase has a preference for ATP more than other nucleoside triphosphate substrates. CaM can bind to recombinant apyrase, but not to the C-terminus of apyrase. This implies that the CaM-binding domain must be in the first 315 amino acids of the N-terminal region of apyrase. We found that one segment from residue 293 to 308 was a good candidate for the CaM-binding domain. This segment 293 FNKCKNTIRKALKLNY 308 has a basic amphiphilic-helical structure, which shows the predominance of basic residues on one side and hydrophobic residues on the other when displayed on a helical wheel plot. Using the gel mobility shift binding assay, this synthetic peptide was shown to bind to CaM, indicating that it is the CaM-binding domain. Both recombinant apyrase and the C-terminus of apyrase can be phosphorylated by a recombinant human protein kinase CKII. Phosphorylation does not affect CaM binding to recombinant apyrase. However, CaM does inhibit CKII phosphorylation of recombinant apyrase and this inhibition can be blocked by 5 mM EGTA.

Peritoneal macrophages from mice fed dietary (n-3) polyunsaturated fatty acids secrete low levels of prostaglandins.

Peritoneal macrophages from mice fed diets containing 10% menhaden oil incorporated significant amounts of n-3 polyunsaturated fatty acids (n-3 PUFA) into cellular lipids, and this lowered arachidonic acid in these lipid classes compared to those from mice fed diets containing 10% coconut oil. The n-3 PUFA-enriched macrophages secreted significantly smaller amounts of prostaglandin E, thromboxane B and 6-keto-prostaglandin F1 alpha when stimulated with opsonized zymosan or phorbol myristate acetate. These studies demonstrated that menhaden oil-enriched diets influence fatty acid composition and prostaglandin synthesis in macrophages.

Alterations in the lipids and prostaglandins in mouse spleen following the ingestion of menhaden oil.

Two groups of male mice were fed for 2 weeks with a semisynthetic diet supplemented with either 10% hydrogenated coconut oil or 10% menhaden oil. The spleen from animals fed with menhaden oil contained significantly higher amounts of polyunsaturated n-3 fatty acids. The n-3 fatty acids reciprocally replaced arachidonic acid in the phospholipids. The synthesis of 6-keto prostaglandin F1 alpha and prostaglandin E2 by spleen tissues were significantly depressed (70-80%) in mice consuming menhaden oil. These studies indicated that n-3 fatty acids can effectively displace arachidonic acid from spleen lipids and thereby affect the synthesis of prostaglandins. The implications of these observations are discussed.