A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide

Peroxidation of membrane lipids results in release of the aldehyde 4-hydroxynonenal (HNE), which is known to conjugate to specific amino acids of proteins and may alter their function. Because accumulating data indicate that free radicals mediate injury and death of neurons in Alzheimer's disease (AD) and because amyloid beta-peptide (A beta) can promote free radical production, we tested the hypothesis that HNE mediates A beta 25-35-induced disruption of neuronal ion homeostasis and cell death. A beta induced large increases in levels of free and protein-bound HNE in cultured hippocampal cells. HNE was neurotoxic in a time- and concentration-dependent manner, and this toxicity was specific in that other aldehydic lipid peroxidation products were not neurotoxic. HNE impaired Na+, K(+)-ATPase activity and induced an increase of neuronal intracellular free Ca2+ concentration. HNE increased neuronal vulnerability to glutamate toxicity, and HNE toxicity was partially attenuated by NMDA receptor antagonists, suggesting an excitotoxic component to HNE neurotoxicity. Glutathione, which was previously shown to play a key role in HNE metabolism in nonneuronal cells, attenuated the neurotoxicities of both A beta and HNE. The antioxidant propyl gallate protected neurons against A beta toxicity but was less effective in protecting against HNE toxicity. Collectively, the data suggest that HNE mediates A beta-induced oxidative damage to neuronal membrane proteins, which, in turn, leads to disruption of ion homeostasis and cell degeneration.     

Quality of life analysis of patients undergoing immunotherapy for allergic rhinitis

Allergic rhinitis has been conservatively estimated to affect 35 million Americans, with an annual US expenditure of more than $2 billion for treatment. Immunotherapy is generally administered to patients with allergic rhinitis when avoidance is impossible or impractical, when pharmacotherapy provides insufficient relief, and/or symptoms span more than one season. Immunotherapy based on quantified testing (e.g., dilutional intradermal testing [SET] or in vitro methods [RAST, ELISA]) allows administration of antigens in a manner that achieves therapeutic antigen doses more rapidly, yet more safely than immunotherapy administered through a schedule that mixes all antigens at the same concentration and advances on an empirical basis. Sixty patients who received at least one year of quantified testing-based immunotherapy were evaluated using a quality of life questionnaire and individual interviews. Changes in physical, social and emotional well-being were determined. Also investigated were changes in productivity and medication usage. The majority of patients noted significant improvement in all areas within four to six months of initiating immunotherapy, and an overwhelming majority felt that such treatment represented a worthwhile investment of their time and money.     

Carbon dioxide field flooding minimizes residual intracardiac air after open heart operations

Transesophageal echocardiographic studies were used to monitor the presence of air bubbles in the heart after open heart operations. After cardiac valvular procedures all 22 patients managed with careful deairing procedures had persistence of air bubbles for at least 30 minutes and usually for 45 minutes. In 56 patients with CO2 field flooding, all foam disappeared in less than 1 minute in 48 patients and the remaining 8 had complete disappearance in 1 to 24 minutes. These observations demonstrate the ineffectiveness of the usual deairing maneuvers and the effectiveness of CO2 field flooding in displacing air.     

Problems associated with rabies preexposure prophylaxis

With the rabies vaccine presently available for preexposure prophylaxis, 20% of all individuals do not have seroconversion following routine immunizations, and 5% are allergic to this vaccine. Two experimental rabies vaccines of cell culture origin offering greater purity and potency were evaluated by means of a double-blind experiment. Thirty-one volunteers who did not have seroconversion or who were allergic to duck embryo rabies vaccine received rabies vaccine produced in either human diploid cell culture (WI-38), or hamster kidney-cell culture. All volunteers had seroconversion within 14 days of receiving a single injection of other experimental vaccine. Clinical side effects were only minor.