α2, α2A, α2B/2C-Adrenoceptor subtype antagonists prevent lipopolysaccharide-induced fever response in rabbits

Exogenous pyrogens, e.g., bacterial lipopolysaccharides (LPS), are thought to stimulate macrophages to release endogenous pyrogens, e.g., TNFα, IL-1 β, and IL-6, which act in the hypothalamus to produce fever. We studied the effect of different α₁⁻ and α₂-adrenoceptor subtype antagonists, applied intraperitoneally, on the febrile response induced by LPS in rabbits. Evidence was obtained that prazosin, an α₁⁻ and α_2B/2C-adrenoceptor antagonist; WB-4101, an α₁⁻ and α_2A-adrenoceptor antagonist; CH-38083, a highly selective α₂-adrenoceptor antagonist (α₂: α₁ > 2000); BRL-44408, an α_2A-adrenoceptor antagonist; and ARC-239, an α_2B/2C⁻ and also α₁-adrenoceptor antagonist, blocked the increase of colonic temperature of the rabbit produced by 2 μg/kg LPS administered intravenously without being able in themselves to affect colonic temperature. In addition, prazosin, WB-4101 and CH-38083 antagonized the fall in skin temperature that occurred at the time when the colonic temperature was rising in control animals injected with LPS. All these results suggest that norepinephrine, through stimulation of both α₁⁻andα₂⁻ (α_2A⁻andα_2B/2C⁻) adrenoceptor subtypes, is involved in producing fever in response to bacterial LPS.     

Aziridines and aziridinium ions in the practical synthesis of pharmaceutical intermediates--a perspective

Recent methods for the synthesis of aziridines and aziridinium ions, the mechanisms of their nucleophilic ring-opening reactions and applications to the practical synthesis of pharmaceutical intermediates are reviewed.     

Use of neoadjuvant and adjuvant therapy to prevent or delay recurrence of prostate cancer in patients undergoing surgical treatment for prostate cancer

There have been improvements in the outcome of patients with clinically localized prostate cancer treated by radical prostatectomy. However, some patients treated with radical prostatectomy will have clinical or biochemical progression. These men are at increased risk of dying of their disease. Identification of patients with adverse features at the time of radical prostatectomy may permit the use of additional multimodality therapies to improve outcomes. Whether this additional multimodality therapy should be administered in the neoadjuvant or adjuvant setting remains controversial. Further, whether a patient at increased risk for progression after radical prostatectomy requires additional therapy before the development of documented progression remains controversial. This article reviews the potential multimodality approaches to prevent or delay recurrence of prostate cancer in patients undergoing surgical treatment for prostate cancer.