Mast cells and their committed precursors are not required for interleukin-3-induced histamine synthesis in murine bone marrow: characteristics of histamine-producing cells

In the present study we investigate the nature of the murine bone marrow cell subset responsible for the marked increase in histamine synthesis induced by interleukin-3 (IL-3). Because mast cells, and eventually their committed precursors, represent a potential source of histamine in this context, we examined their possible participation in this biologic activity with particular attention. We provide evidence that neither of these populations respond to IL-3 in terms of histamine synthesis and that other differentiated end cells or stromal components of the bone marrow are also not involved in this phenomenon. Starting from these findings, we further characterized the immature hematopoietic compartment responsible for IL-3-induced histamine synthesis using fluorescence-activated cell sorter (FACS) sorting based on rhodamine retention or wheat germ agglutinin (WGA) affinity. These procedures have allowed us to ascribe the following features to histamine-producing cells: (1) They belong to a low-density, progenitor- enriched bone marrow subset containing cells of relatively important size and internal structure. (2) The highest histamine levels are generated by the rhodamine-bright fraction of this population, while the most primitive rhodamine-dull cells do not express this biologic activity. (3) Histamine-producing cells do not copurify with colony- forming units in spleen day 7 and day 12 in WGA-bright fractions. (4) Their enrichment is associated with increased frequencies of cells forming colonies in methylcellulose (CFU-C), suggesting the involvement of several progenitors with partially limited differentiation potential in this biologic activity.     

Properties of the ventricular adrenergic signal transduction system during ontogeny of spontaneous hypertension in rats

The purpose of this study was to characterize adrenergic receptors and associated G proteins in ventricles of spontaneously hypertensive rats (SHRs) at different stages of development. The beta- and alpha1-adrenoceptor densities and subtype distribution, and beta-adrenoceptor-G protein coupling were studied by radioligand binding, and levels of G(Salpha), G(ialpha), and G(q/11alpha) protein species were determined by Western blotting in SHRs and Wistar-Kyoto (WKY) control rats aged 3.5 weeks, 3 months, and 8 months. In 3.5-week-old SHRs, both the beta-adrenoceptor density and the percentage of agonist high-affinity binding sites were higher than in age-matched WKY rats. The beta1/beta2-subtype distribution, the alpha1-adrenoceptor density, and the alpha1B/alpha1A-subtype distribution were similar in rats of both strains at all ages. Although essentially no differences in G(salpha) levels between SHRs and WKY rats were detected, higher G(ialpha) and lower Gq/1alpha concentrations were found in 3.5-week-old SHRs. In 3-month-old SHRs, increased levels of Gq/11alpha proteins were observed. In 8-month-old SHRs, none of the parameters was different from those of controls. We conclude that the differences in properties of the adrenergic signal transduction system between SHRs and WKY rats are exclusively observable before and at the onset of the overt hypertension. Moreover, the hypertensive genotype apparently affects G proteins more readily than adrenoceptors.     

How is an Electronic Screening and Brief Intervention Tool on Alcohol Use Received in a Student Population? A Qualitative and Quantitative Evaluation

Background

A previous study among Antwerp college and university students showed that more male (10.2%–11.1%) than female (1.8%–6.2%) students are at risk for problematic alcohol use. The current literature shows promising results in terms of feasibility and effectiveness for the use of brief electronic interventions to address this health problem in college and university students. We evaluated this type of intervention and cite existing literature on the topic.

Objective

To develop a website, www.eentjeteveel.be, to motivate college and university students with problematic alcohol use to reduce alcohol consumption and increase their willingness to seek help.

Method

The website contained a questionnaire (Alcohol Use Disorders Identification Test [AUDIT]) for students to test their alcohol use. According to their answers, the students immediately received personalized feedback (personal AUDIT score and additional information on risks associated with alcohol use) and a suggestion for further action. Afterward, students could send an email to a student counselor for questions, guidance, or advice. To obtain in-depth qualitative information on the opinions and experiences of students, we held 5 focus group discussions. The topics were publicity, experiences, impressions, and effects of the website. We analyzed the quantitative results of the online test in SPSS 15.0.

Results

More than 3500 students visited www.eentjeteveel.be; over half were men (55.0%). A total of 34 students participated in the focus group discussions. The mixture of quantitative and qualitative methods to evaluate the intervention allowed a thorough analysis and provided complementary results. The intervention was well received by the student population. However, some minor aspects should be reconsidered, such as website publicity and providing students with options that were added after intermediate evaluation. The intervention increased the motivation of students to think about their alcohol use but could not stimulate them to change their behavior. The website attracted relatively more male than female students and more students in the high-risk group than in the low-risk group. The high-risk group was more inclined to seek advice or guidance (23/400, 6%; χ² _{2 = 32.4,} P < .001) than the low-risk group (34/1714, 2%; χ² _{2 = 32.4,} P < .001).

Conclusions

We gained unique insight into students’ experiences, opinions, and perceptions with regard to the intervention. The results show that the intervention was positively received in the population, and the willingness to seek help was increased. However, real behavior change needs further research. The results of this study can assist health providers and researchers in better understanding college and university students’ perceptions of eHealth initiatives.     

Further evaluation of the biological activity of the unique gonadotropin-releasing hormone peptide in the guinea pig brain

In this study we compared the biological activity of a unique form of gonadotropin-releasing hormone (GnRH) in the brain of the guinea pig (gpGnRH) with mammalian GnRH (mGnRH). In gpGnRH, the highly conserved histidine in position 2 (His(2)) and leucine in position 7 (Leu(7)) are substituted by tyrosine and valine, respectively. The gpGnRH was less potent than mGnRH in stimulating the release of luteinizing hormone (LH) in vivo in the guinea pig and displayed only low activity in the rat. The gpGnRH was more rapidly degraded by serum proteolytic enzymes than mGnRH. It is concluded that gpGnRH displays lower biological activity than mGnRH in both rat and guinea pig, which may be due in part to its greater susceptibility to proteolytic degradation besides differences in receptor affinity and/or activation.