Metallothionein gene expression in rats: tissue-specific regulation by dietary copper and zinc

Regulation of metallothionein gene expression by dietary zinc and copper was examined in rat liver, kidney, intestine and brain using a 3 X 3 factorial design. Purified diets containing 5, 30 and 180 mg Zn/kg and 1, 6 and 36 mg Cu/kg were fed for 2 wk. Serum concentrations of copper and zinc were lower at the lowest intakes of either metal than at normal or supplemental levels. Kidney metallothionein levels were proportional to dietary zinc, being 50% less in the 5 mg Zn/kg group than in those fed the highest zinc intake. Metallothionein mRNA was measured by dot blot hybridization to a 32P-labeled oligonucleotide DNA probe representing the terminal 5' sequence of the metallothionein gene. In kidney the number of metallothionein mRNA molecules per cell increased four- to five-fold (from 4 to 29 molecules per cell) with increasing dietary zinc. A less pronounced effect on metallothionein mRNA was observed in response to dietary copper. At the lowest copper intake level and highest intake of zinc intestinal metallothionein mRNA was sevenfold greater than in any other group. Liver and brain did not respond appreciably to the dietary levels of copper and zinc that were fed. Chromatography showed that copper and zinc content of renal metallothionein was directly related to the dietary levels fed. In kidney, both metallothionein-1 and -2 genes were expressed.     

Zoonotic tuberculosis: on the decline

Mycobacterium bovis is a zoonotic member of the Mycobacterium tuberculosis complex responsible for a clinical syndrome indistinguishable from that due to M. tuberculosis. In Australia, infection with M. bovis has historically been associated with employment in the livestock industry or immigration from countries in which animal disease is endemic. It currently accounts for 0.2% of all human cases of tuberculosis within Australia. This paper describes a case of pulmonary M. bovis in a butcher and reviews factors responsible for the declining incidence of this disease in Australia.     

Gastrointestinal factors influencing zinc absorption and homeostasis

Diet-derived luminal factors have a major influence on zinc available for uptake across the apical membrane of enterocytes. Malabsorption and possibly intestinal microbiota limit this zinc availability. The transporter ZIP4 is expressed along the entire gastrointestinal tract and acts as a major processor of dietary zinc for loading into enterocytes from the apical membrane. Zip4 and other Zip family genes expressed in the gastrointestinal tract are up-regulated in periods of dietary zinc restriction. This provides for powerful homeostatic control. The transporter ZIP14 is up-regulated along the entire gastrointestinal tract by proinflammatory conditions. Intracellular transporters such as ZnT7, influence the transcellular movement of zinc across the enterocyte. Metallothionein, an intracellular metal buffer, and the transporter ZnT1 at the basolateral membrane, regulate the amount of zinc released to the portal circulation for systemic distribution. Pancreatic release of zinc by acinar cells is through the secretory process and apical membrane and involves transporters ZnT2 and ZnT1, respectively. Expression of both transporters is zinc-responsive. Enterocytes and acinar cells constitutively express Zip5 at the basolateral membrane, where it may serve as a monitor of zinc status.     

Energy‐Dense Formulae May Slow Gastric Emptying in the Critically Ill

Background: Enteral feed intolerance occurs frequently in critically ill patients and can be associated with adverse outcomes. “Energy‐dense formulae” (ie, >1 kcal/mL) are often prescribed to critically ill patients to reduce administered volume and are presumed to maintain or increase calorie delivery. The aim of this study was to compare gastric emptying of standard and energy‐dense formulae in critically ill patients. Methods: In a retrospective comparison of 2 studies, data were analyzed from 2 groups of patients that received a radiolabeled 100‐mL “meal” containing either standard calories (1 kcal/mL) or concentrated calories (energy‐dense formulae; 2 kcal/mL). Gastric emptying was measured using a scintigraphic technique. Radioisotope data were collected for 4 hours and gastric emptying quantified. Data are presented as mean ± SE or median [interquartile range] as appropriate. Results: Forty patients were studied (n = 18, energy‐dense formulae; n = 22, standard). Groups were well matched in terms of demographics. However, patients in the energy‐dense formula group were studied earlier in their intensive care unit admission (P = .02) and had a greater proportion requiring inotropes (P = .002). A similar amount of calories emptied out of the stomach per unit time (P = .57), but in patients receiving energy‐dense formulae, a greater volume of meal was retained in the stomach (P = .045), consistent with slower gastric emptying. Conclusions: In critically ill patients, the administration of the same volume of a concentrated enteral nutrition formula may not result in the delivery of more calories to the small intestine over time because gastric emptying is slowed.     

Pleasure During Adolescents’ Most Recent Partnered Sexual Experience: Findings from a U.S. Probability Survey

Compared to studies on sexually transmitted infections and pregnancy prevention, sexual pleasure has received limited attention in the adolescent sexual development literature. In the present study, we used data from 157 adolescents (66 females; 14 to 17 years old), with a partnered sexual experience in the past 12 months to explore adolescents’ sexual pleasure. First, we examined adolescents’ perceptions of pleasure during their most recent partnered sexual experience. We then used information about those sexual experiences to identify correlates of sexual pleasure. Adolescents’ reports of sexual pleasure were mixed. Although 17.8% reported their sexual experience was extremely pleasurable and 36.5% reported it was quite pleasurable, 26.6% indicated moderate pleasure, 13.1% a little pleasure, and 3.3% reported no pleasure. Sexual pleasure was primarily associated with aspects of sexual experiences that reflected socioemotional intimacy and desire. Specifically, cuddling with partners, emotional intimacy, and wantedness were all associated with greater sexual pleasure. Additionally, adolescents found sex more pleasurable when it occurred with a friend, but less pleasurable when it involved genital rubbing. Most sexual behaviors, having experienced orgasm, and the situational context of sexual experiences were not associated with sexual pleasure. Thus, specific sexual behaviors and orgasm may have less impact on sexual pleasure than feelings of emotional intimacy and desire. The diversity of perceived sexual pleasure and its associations with intimacy and desire suggest that, during adolescence, partnered sexual experiences are not primarily motivated by anticipated physical pleasure.

     

The Influence of Attraction to Partner on Heterosexual Women’s Sexual and Relationship Satisfaction in Long-Term Relationships

Previous research has consistently found that attraction is important in the formation of relationships though research on attraction in long-term relationships is less well understood. This article examined the predictive value of self-reported attraction to partner and change in attraction to partner on sexual and relationship satisfaction in 176 women in committed heterosexual relationships using online survey methodology. Participants’ age ranged from 21 to 56 (M = 34.5) years and their relationship length ranged from 5 to 35 (M = 11.75) years. Hierarchical multiple regression results indicated that change in attraction to partner was the most salient predictor of sexual satisfaction, with current attraction to partner also related to women’s sexual satisfaction, accounting for 20 % of the variance. Current attraction to partner was the only significant predictor of women’s relationship satisfaction, accounting for 22 % of the variance. Additionally, attraction variables accounted for variance above and beyond the impact of relationship and sexual satisfaction. These findings suggest that self-reported attraction to partner is an important contributor to women’s satisfaction outcomes in long-term relationships. Further studies in the area of attraction to partner that include couple dynamics and longitudinal data are encouraged and implications for therapists, clinicians, and educators are discussed.     

Long-Term Stability of Anti-Vascular Endothelial Growth Factor (a-VEGF) Biologics Under Physiologically Relevant Conditions and Its Impact on the Development of Long-Acting Delivery Systems

The port delivery system with ranibizumab (PDS) is an investigational long-acting drug delivery system for the continuous release of ranibizumab, an anti-VEGF biologic, in the vitreous humor. The efficacy of the PDS implant relies on the maintenance of long-term drug stability under physiological conditions. Herein, the long-term stability of three anti-VEGF biologics - ranibizumab, bevacizumab and aflibercept - was investigated in phosphate buffered saline (PBS) at 37 °C for several months. Comparison of stability profiles shows that bevacizumab and aflibercept are increasingly prone to aggregation whereas ranibizumab undergoes minimal aggregation. Ranibizumab also shows the smallest loss in antigen binding capacity after long-term incubation in PBS. Even though the aggregated forms of bevacizumab and aflibercept bind to VEGF, the consequences of aggregation on immunogenicity, implant function and efficacy are unknown. These results highlight the importance of maintaining long-term drug stability under physiologically relevant conditions which is necessary for achieving efficacy with an in vivo continuous drug delivery device such as the PDS implant.