EFFECTS OF 5HT2 RECEPTOR ANTAGONISTS ON RESPONSES TO POTASSIUM DEPOLARIZATION IN RAT ISOLATED AORTA

1. In order to determine whether 5HT₂ receptor antagonists can modify Ca²⁺ uptake via voltage-operated Ca²⁺ channel (VOC) in arterial smooth muscle, a comparative study of the effects of selected Ca²⁺ uptake blockers and 5HT₂ receptor antagonists on K⁺-induced contractions of rat aortic strip was undertaken. 2. The antagonist drugs studied included the Ca²⁺ uptake blockers verapamil, nifedipine, felodipine, diltiazem and cin-narizine, the 5HT₂ receptor antagonists cyproheptadine, ritanserin, mianserin, and ketanserin and the α₁-adrenoceptor antagonist prazosin. 3. With the notable exception of prazosin, each of these compounds diminished K⁺-induced aortic responses. 4. The following order of potencies (mean IC₅₀ values in mol/L) was established: felodipine (7.0 × 10^-11) >nifedipine (4.8 × 10^-9) >verapamil (5.5 × 10^-8) >cyproheptadine (6.2 × 10^-8) > diltiazem (4.1 × 10^-7) >cinnarizine (1.3 × 10^-6) >ritanserin (1.8 × 10^-6) >ketanserin (9.0 × 10^-6) > mianserin (2.0 × 10^-5). 5. The results suggest that antagonists of 5HT₂ receptors can modulate Ca²⁺ uptake via VOC in rat aorta.     

Predominant usage of the proximal poly(A) site in alpha mRNAs is not intrinsic to the 3' termini

The maturation of IgM-expressing B cells to IgM-secreting plasma cells is associated with both an increase in mu mRNA and the ratio of secreted to membrane forms of mu mRNA. In contrast, previous studies demonstrated that in vitro the secreted form of alpha mRNA (alpha s mRNA) predominates regardless of the stage of B cell differentiation. The present study demonstrates that alpha s mRNA predominates in both B cells derived from the germinal centers of murine Peyer's patches and in the functional IgA memory population, suggesting that in vitro events accurately represent the generation of a secretory IgA response in vivo. Although the predominant usage of the alpha s poly(A) site is due to RNA processing, it does not depend on either the alpha s poly(A) site, the 3' splice site associated with the exon encoding the membrane exon of IgA (alphaM) or the alphaM poly(A) sites. Analysis of the sequence of the intron between the alpha s terminus and alphaM (alpha s- alphaM intron) demonstrates the existence of several potential regulatory elements. Furthermore, the effects of deletions within the alpha s-alphaM intron on 3' terminus usage demonstrate that the predominant usage of the proximal terminus is not strictly dependent on the length of the intron. Together with previous work, these observations support the idea that choice of 3' terminus for all Ig heavy chain genes is regulated by a similar mechanism, but specific sequences within a heavy chain gene can impinge upon that mechanism.      

A strategy for assessing workplace exposures to nanomaterials

This article describes a highly tailorable exposure assessment strategy for nanomaterials that enables effective and efficient exposure management (i.e., a strategy that can identify jobs or tasks that have clearly unacceptable exposures), while simultaneously requiring only a modest level of resources to conduct. The strategy is based on strategy general framework from AIHA? that is adapted for nanomaterials and seeks to ensure that the risks to workers handling nanomaterials are being managed properly. The strategy relies on a general framework as the basic foundation while building and elaborating on elements essential to an effective and efficient strategy to arrive at decisions based on collecting and interpreting available information. This article provides useful guidance on conducting workplace characterization; understanding exposure potential to nanomaterials; accounting methods for background aerosols; constructing SEGs; and selecting appropriate instrumentation for monitoring, providing appropriate choice of exposure limits, and describing criteria by which exposure management decisions should be made. The article is intended to be a practical guide for industrial hygienists for managing engineered nanomaterial risks in their workplaces.