Sulfur-related air pollutants induce the generation of platelet-activating factor, 5-lipoxygenase- and cyclooxygenase-products in canine alveolar macrophages via activation of phospholipases A2

Recent studies have shown that long-term in vivo exposure of dogs to neutral sulfur(IV)/sulfite aerosols induces mild inflammatory reactions, whereas the combination of neutral sulfite with acidic sulfur(VI)/sulfate aerosols evokes less pronounced effects. To understand underlying mechanisms, we studied in vitro the role of lipid mediators in the responses of alveolar macrophages (AMs) to sulfur-related compounds under neutral (pH 7) or moderate acidic (pH 6) conditions. Canine AMs incubated with sulfite at pH 7 released threefold higher amounts of platelet-activating factor than control (P < 0.005). Generation of arachidonic acid, leukotriene B4, 5-hydroxy-eicosatetraenoic acid, prostaglandin E2, thromboxane B2 and 12-hydroxyheptadecatrienoic acid increased twofold (P < 0.0005). However, these metabolites remained unchanged following incubation of AMs with sulfite at pH 6 or with sulfate at pH 7 or pH 6. Mediator release by sulfite-treated AMs at pH 7 stimulated respiratory burst activity of neutrophils. Inhibition of MAPK pathway by PD 98059, of cytosolic (cPLA2) and secretory phospholipases A2 by AACOCF3 and thioetheramide-PC, respectively, reduced sulfite-induced eicosanoid formation in AMs. Sulfite activated cPLA2 activity twofold at pH 7. This mechanism of sulfite-stimulated responses in phospholipid metabolism predicts that chronic exposure to sulfur(IV)/sulfite is associated with a considerable health risk.     

A microdialysis study of the effects of the nicotinic agonist RJR-2403 on cortical release of acetylcholine and biogenic amines

Transcortical dialysis was employed to investigate the effects of subcutaneous (s.c.) injections of RJR-2403 (1.2-7.2 mumol/kg) on extracellular levels of acetylcholine (ACh), norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in rat. Systemic administration of RJR-2403 produced a 90% increase of cortical extracellular ACh levels that persisted for up to 90 minutes after injection. Norepinephrine and DA release were increased 124% and 131% above basal values, respectively. Serotonin (5-HT) levels in the dialysate were also significantly elevated by RJR-2403 (3.6 mumol/kg, s.c.) 70% above baseline at 90 minutes post-injection. Comparison of these responses to those of (-)nicotine from a previous study reveals little difference between the two compounds in their ability to influence cortical neurotransmitter release following systemic administration.     

Immunolocalization of natriuretic peptide receptor B in the rat kidney

The natriuretic peptide receptor (NPR) family consists of three receptor subtypes: two transmembrane forms that contain a guanylyl cyclase intracellular domain (NPR-A and NPR-B), and one truncated form (NPR-C). Because of the lack of specific agonists and antagonists for each receptor subtype and to the difficulty to detect the presence of small quantities of NPR-B by ligand binding studies, polyclonal antibodies against a peptide whose sequence was chosen from a region of the extracellular domain of rat NPR-B that is not homologous to sequences in NPR-A and NPR-C were developed. Western blotting with affinity-purified anti-NPR-B (413-426)-Tyr revealed a polypeptide of approximately 120 kD on COS-1 cell membranes transfected with rat NPR-B cDNA. The antibody recognized a second polypeptide, approximately 5 to 10 kD smaller, which probably represents the unglycosylated receptor. Anti-NPR-B (413-426)-Tyr did not show crossreactivity to any other NPR. Western blotting analysis with anti-NPR-B (413-426)-Tyr also identified a protein of appropriate size in renal vascular membranes. These results were supported by immunohistochemistry findings that demonstrated staining for NPR-B on papillary and medullary capillaries, glomeruli, and renal arteries. This study concludes that NPR-B is present in the rat kidney, although it was only detected in vascular structures.     

Life cycle of Ixodes minor (Acari: Ixodidae) in the laboratory

OBJECTIVE: It is commonly believed that the full moon exerts an influence on violence and aggression in psychiatric settings. The literature to date is contentious. This study used a robust methodology to examine the hypothesis that there was an increased frequency of violent and aggressive behaviour among hospitalised psychiatric clients at the time of the full moon. METHOD: Prospective data were collected in five inpatient psychiatric settings across the Northern Sydney Area Health Service. Morrison's hierarchy of violence and aggression was used to rate behaviour. Lunar phases were clearly defined and Poisson regression used to examine relationships between lunar phase and violence. Extraneous temporal variation was considered. RESULTS: No significant relationship was found between total violence and aggression or level of violence and aggression and any phase of the moon. CONCLUSION: Future research could profitably examine the implications of a belief in the lunar effect among health workers in the face of evidence that no relationship exists between violence, aggression and the lunar cycle.     

The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community

BACKGROUND: Despite recommendations for annual vaccination against influenza, more than half of elderly Americans do not receive this vaccine. In a serial cohort study, we assessed the efficacy and cost effectiveness of influenza vaccine administered to older persons living in the community. METHODS: Using administrative data bases, we studied men and women over 64 years of age who were enrolled in a large health maintenance organization in the Minneapolis-St. Paul area. We examined the rate of vaccination and the occurrence of influenza and its complications in each of three seasons: 1990-1991, 1991-1992, and 1992-1993. Outcomes were adjusted for age, sex, diagnoses indicating a high risk, use of medications, and previous use of health care services. RESULTS: Each cohort included more than 25,000 persons 65 years of age or older. Immunization rates ranged from 45 percent to 58 percent. Although the vaccine recipients had more coexisting illnesses at base line than those who did not receive the vaccine, during each influenza season vaccination was associated with a reduction in the rate of hospitalization for pneumonia and influenza (by 48 to 57 percent, P < or = 0.002) and for all acute and chronic respiratory conditions (by 27 to 39 percent, P < or = 0.01). Vaccination was also associated with a 37 percent reduction (P = 0.04) in the rate of hospitalization for congestive heart failure during the 1991-1992 season, when influenza A was epidemic. The costs of hospitalization for all types of illness studied were lower in the vaccinated group during 1991-1992 (range of reduction, 47 to 66 percent; P < 0.005) and for acute and chronic respiratory conditions and congestive heart failure in 1990-1991 (reductions of 37 percent and 43 percent, respectively; P < or = 0.05). Direct savings per year averaged $117 per person vaccinated (range, $21 to $235), with cumulative savings of nearly $5 million. Vaccination was also associated with reductions of 39 to 54 percent in mortality from all causes during the three influenza seasons (P < 0.001). CONCLUSIONS: For elderly citizens living in the community, vaccination against influenza is associated with reductions in the rate of hospitalization and in deaths from influenza and its complications, as compared with the rates in unvaccinated elderly persons, and vaccination produces direct dollar savings.     

Genetic transformation of Vitreoscilla sp

Of all the methods customarily used to transform E. coli we found only electroporation to be effective for transformation of the Gram-negative bacterium Vitreoscilla, yielding 5.10(5) transformants/microgram of plasmid DNA. The conditions used were close to those described for E. coli E. coli plasmids are stably maintained in Vitreoscilla. This is the first report of exogenous DNA transfer in Vitreoscilla which opens the way for the application of recombinant-DNA techniques to study this unique group of organisms.     

Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I trial

BACKGROUND: Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes. We examined the activated partial thromboplastin time (aPTT) in 29,656 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial and analyzed the relationship between the aPTT and both baseline patient characteristics and clinical outcomes. METHODS AND RESULTS: Intravenous heparin was administered as a 5000-U bolus followed by an initial infusion of 1000 U/h, with dose adjustment to achieve a target aPTT of 60 to 85 seconds. aPTTs were collected 6, 12, and 24 hours after thrombolytic administration. Higher aPTT at 24 hours was strongly related to lower patient weight (P < .00001) as well as older age, female sex, and lack of cigarette smoking (all PT< .0001). At 12 hours, the aPTT associated with the lowest 30-day mortality, stroke, and bleeding rates was 50 to 70 seconds. There was an unexpected direct relationship between the aPTT and the risk of subsequent reinfarction. There was a clustering of reinfarction in the first 10 hours after discontinuation of intravenous heparin. CONCLUSIONS: Although the relationship between aPTT and clinical outcome was confounded to some degree by the influence of baseline prognostic characteristics, aPTTs higher than 70 seconds were found to be associated with higher likelihood of mortality, stroke, bleeding, and reinfarction. These findings suggest that until proven otherwise, we should consider the aPTT range of 50 to 70 seconds as optimal with intravenous heparin after thrombolytic therapy.     

Deep brain stimulation for essential tremor

We examined the effects and safety of deep brain stimulation (DBS) as a treatment for essential tremor (ET). Ten ET patients with disabling medication-refractory tremor underwent stereotactic implantation of a DBS lead in the left Vim thalamic nucleus and completed a 6-month follow-up. The Clinical Tremor Rating Scale and disability assessments were performed at baseline, 1-, 3-, and 6-month follow-up. There were significant improvements in dressing, drinking, eating, bathing, and handwriting as reported by the subjects. Tremor severity, writing, pouring, and spiral and line drawing were significantly improved as rated by the examiner. Improvements persisted through the 6-month follow-up period. Although global disability significantly lessened in the group as a whole, one subject with hand-finger tremor accentuated by writing had no change in disability status. In this 6-month open-label study, DBS was effective and safe in reducing tremor and functional disability in ET.     

Inhibition of anthracycline semiquinone formation by ICRF-187 (dexrazoxane) in cells

The formation of semiquinone free radicals of doxorubicin, epirubicin, daunorubicin, and idarubicin was measured by electron paramagnetic resonance (EPR) spectroscopy in hypoxic suspensions of chinese hamster ovary (CHO) cells. The amount of semiquinone produced was in the order idarubicin > doxorubicin > daunorubicin > epirubicin. The idarubicin semiquinone signal was both the fastest to be formed and to decay. Idarubicin, which was the most lipophilic of the anthracyclines studied, also displayed the fastest fluorescence-measured cellular uptake of drug. Thus, it was concluded that semiquinone formation was dependent upon the rate of cellular uptake. Lysed cell suspensions were also shown to be capable of producing the doxorubicin semiquinone in the presence of added NADPH. The cardioprotective agent dexrazoxane (ICRF-187) was observed to decrease the amount of doxorubicin semiquinone observed in cell suspensions. Dexrazoxane also decreased the amount of doxorubicin semiquinone observed in the NADPH-lysed cell suspension mixture. Neither bipyridine nor deferoxamine decreased NADPH-dependent doxorubicin semiquinone formation. These results suggest that dexrazoxane does not decrease doxorubicin semiquinone formation through an iron complex formed from hydrolyzed dexrazoxane. Dexrazoxane may be inhibiting an NADPH-dependent enzyme.