Therapeutic options for severe, refractory status asthmaticus: inhalational anaesthetic agents, extracorporeal membrane oxygenation and helium/oxygen ventilation

Despite improvements in supportive care, the mortality and morbidity of asthma remain constant. The risks and incidence of morbidity related to barotrauma remain high in patients that require mechanical ventilation. The authors present three alternative strategies including the inhalation of anaesthetic agents, helium/oxygen ventilation, and extracorporeal membrane oxygenation which may be beneficial when 'conventional therapies' fail in the intubated patient with status asthmaticus.     

Aldicarb Immunotoxicity: Functional Analysis of Cell-Mediated Immunity and Quantitation of Lymphocyte Subpopulations

Aldicarb Immunotoxicity: Functional Analysis of Cell-MediatedImmunity and Quantitation of Lymphocyte Subpopulations. THOMAS,P., RATAJCZAK, H., DEMETRAL, D., HAGEN, K., AND BARON, R. (1990).Fundam. Appl. Toxicol. 15, 221–230. Adult female B6C3F1mice received distilled water only or water containing 1.0,10, or 100 ppb of aldicarb daily for 34 days. The target concentrationof aldicarb present in the 100 ppb dosing solution was analyticallyverified. To further develop an immune profile of this compound,following aldicarb exposure, the ability of splenic naturalkiller cells and specifically sensitized cytotoxic T-lymphocytesto lyse YAC-1 lymphoma and P815 tumor cells, respectively, wasevaluated. To supplement the functional assays, the impact ofaldicarb exposure on the percentages and absolute numbers oftotal T-cells, T-suppressor, T-helper, and B-cells was evaluated.The absence of statistically significant effects on any of theseparameters supports earlier reports that aldicarb does not resultin adverse effects on the immune system of mice.     

Endothelial cell junctions and the regulation of vascular permeability and leukocyte transmigration

Summary.  The endothelial lining of the vasculature forms the physical barrier between the blood and underlying tissues. Junctions between adjacent endothelial cells are dynamically modulated to sustain vascular homeostasis and to support the transendothelial migration of leukocytes during inflammation. A variety of factors initiate intracellular signaling pathways that regulate the opening and resealing of junctional complexes. This review focuses on three primary signaling pathways initiated within endothelial cells by the binding of vasoactive factors and leukocyte adhesion: Rho GTPases, reactive oxygen species, and tyrosine phosphorylation of junctional proteins. These pathways converge to regulate junctional permeability, either by affecting the stability of junctional proteins or by modulating their interactions. Although much progress has been made in understanding the relationships of these pathways, many questions remain to be answered. A full understanding of the signaling cascades that affect endothelial junctions should identify novel therapeutic targets for diseases that involve excessive permeability or inappropriate leukocyte infiltration into tissues.     

EFFECT OF DOPAMINE AND A DOPAMINE D-1 RECEPTOR AGONIST ON PULSATILE THYROTROPHIN SECRETION IN NORMAL WOMEN

The inhibitory effect of a pharmacological dose of dopamine and the specific dopamine D-1 receptor agonist fenoldopam on basal and pulsatile TSH secretion was investigated in normal women. The TSH response to fenoldopam and subsequent releasing hormone administration was also studied. Six women received placebo or dopamine infusion (4.0 micrograms/kg min) for 17 h. After 9 h, blood samples were collected every 10 min between 0800 and 1600 h for measurement of TSH. Eight women received 8-h (0900-1700 h) infusions of either fenoldopam (0.5 micrograms/kg min) or placebo. After 7 h of infusion 10 micrograms TRH, 5 micrograms GnRH and 25 micrograms CRF was given i.v. Blood samples were collected every 10 min. Dopamine infusion as well as fenoldopam infusion significantly reduced both mean basal TSH secretion and TSH pulse frequency compared with corresponding control infusions (P less than 0.05). However, while the effect on TSH pulsatility was comparable (P greater than 0.05), the percentage decrease in basal TSH levels after 16 h of dopamine infusion was 51 +/- 16% (mean +/- SD) and after 7 h of fenoldopam infusion 19 +/- 12% (P less than 0.05). Neither of the drugs affected TSH pulse amplitude and fenoldopam did not influence TRH-stimulated TSH release (P greater than 0.05). The results suggest that dopamine D-1 receptors are involved in modulation of TSH pulsatility probably at the hypothalamic level. It is argued that dopaminergic inhibition of basal TSH secretion and TSH pulsatility is predominantly regulated through dopamine D-2 receptors at the pituitary level, and through D-1 receptors at the hypothalamic level, respectively.