Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon

We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose- dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.      

Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice

We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow mutation (A(vy)) of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TGxAC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TGxAC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line results in an approximately 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition, TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice.      

The fitting of scheffé-type models for estimating solubilities of multisolvent systems

In pharmaceutical studies it is often necessary to dissolve a slightly polar drug in a mixture of water and one or more cosolvents, such as ethanol, glycerol, and propylene glycol, to increase the drug's solubility. It is also of interest to knowwhether a maximum in the solubility profile of the drug exists in the mixture of solvents and if so, where.

Scheffé-type models are particular forms of polynomial equations that can be used with variables that are expressed as proportions of the total mixture. These models are simple in form, yet are extremely versatile in terms of modeling the linear and nonlinear blending properties of the constituents in the mixtures. Several data sets are presented to illustratethe fitting of the Scheffé-type models for modeling the solubility of multisolvent systems.     

Flow Imaging: Moving Toward Best Practices for Subvisible Particle Quantitation in Protein Products

The potential impact of subvisible particles (SVPs) in protein therapeutic products has received a great deal of attention recently. As a result, new analytical methods have emerged to characterize and quantify SVPs. Among these, flow imaging (also called flow microscopy) has been widely employed. As we have used both FlowCAM® and Micro-Flow Imaging? in a variety of development projects, we wished to share our experiences and observations, with the intention of fostering a discussion that will lead to best practices for the use of flow imaging to quantify SVP levels in biopharmaceuticals. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1133–1134, 2013     

The Influence of TMJ and Central Incisor Sensory Impairment on Bite Force Discrimination

In this study the authors temporarily altered sensation around the upper and lower front teeth as well as within the temporomandibular joints of 12 subjects. The purpose of the study was to determine the effect of such impairment by comparing bite force discrimination scores obtained under these experimental conditions with scores obtained under a normal non-anesthetized condition. A specially designed strain gauge scale was constructed for the measurement of incisor bite force. The subjects' abilities to discriminate differences in their biting forces were assessed under the following four experimental conditions: 1. Normal (no anesthetization).

2. Regional block to the upper and lower anterior teeth.

3. Bilateral regional block of the TMJs.

4. A combination regional block of the anterior teeth and the TMJs. Bite force discrimination was found to be significantly impaired (P<.05) only in the two conditions in which the teeth were anesthetized. These findings suggest that the periodontal ligament (PDL) provides sensory feedback relative to bite force discrimination whereas the TMJs do not.

     

Bite Force Discrimination with Mandibular Movement

This study investigates the influence of jaw movement on bite force discrimination by comparing subjects' performances during static and dynamic conditions. The authors had hypothesized that exerting bite force with mandibular movement might activate the dynamic sensory receptors within the TMJs and the proprioceptors in the jaw elevator muscles. This might then allow for finer discriminations in performance than would be possible under a condition of static bite force involving no jaw movement. The results, however, revealed no significant difference in bite force discrimination between the two conditions.     

Psychosocial predictors of long-term mortality among women with suspected myocardial ischemia: the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation

This paper evaluated long-term associations between psychosocial factors and premature mortality among women with suspected coronary artery disease (CAD). We tracked total mortality events over a median 9.3 years in a cohort of 517 women [baseline mean age = 58.3 (11.4) years]. Baseline evaluations included coronary angiography, psychosocial testing, and CAD risk factors. Measures included the Spielberger Trait Anxiety Scale, Beck Depression Inventory, self-rated health, and Social Network Index. Cox regression analysis was used to assess relationships. Covariates included age, CAD risk factors, and CAD severity. BDI scores (HR 1.09, 95 % CI 1.02–1.15), STAI scores (HR .86, 95 % CI .78–.93), and very good self-rated health (relative to the poor self-rated health group; HR .33, 95 % CI .12–.96) each independently predicted time to mortality outcomes in the combined model. SNI scores (HR .91, 95 % CI .81–1.06) and other self-rated health categories (i.e., fair, good, and excellent categories) were not significant mortality predictors after adjusting for other psychosocial factors. These results reinforce and extend prior psychosocial research in CAD populations.