Moderation of physiological stress responses by personality traits and daily hassles: less flexibility of immune system responses

Previously we demonstrated that stressors varying on the dimension of mental effort and controllability have distinctive effects on cardiovascular, endocrine and immune system responses. The purpose of the present study was to relate individual differences in physiological stress responsivity to task appraisal and stress-induced mood changes (issue 1), trait characteristics (issue 2) and daily hassles (issue 3). Appraisal and mood changes did not mediate the differential effects of the stressors. The trait characteristics, aggression and external locus of control and daily hassles moderated the effect of the stressor on physiological parameters, especially immune parameters. Moreover, the moderation effect was different in the high versus the low effort stress task. High aggression, high external locus of control and more daily hassles were associated with increased reactivity in the low effort condition and decreased reactivity in the high effort condition, which is suggested to reflect less differentiated responding to changing task demands and hence, less flexibility in the immune system.     

Ca2+ and Sr2+ activation: Comparison of cardiac and skeletal muscle contraction models

The mechanism of contraction in rabbit fast-twitch, and bovine and rabbit cardiac muscle was examined using functionally skinned fibers, ATPase activity of myofibrils, and cardiac or skeletal troponintropomyosin regulated actin heavy meromyosin. The Ca²⁺ and Sr²⁺ activation properties for the different measures of contraction were evaluated. (1) Tension in rabbit and bovine cardiac skinned fibers and rabbit cardiac myofibrillar ATPase were activated equally well by either Ca²⁺ or Sr²⁺. By contrast, rabbit adductor magnus (fast-twitch) skinned fibers required substantially higher [Sr²⁺] than [Ca²⁺] for activation, as did rabbit myofibrils from back muscle (fast-twitch). (2) Substantially more Sr²⁺ than Ca²⁺ was also required for activation of skeletal muscle actin heavy meromyosin ATPase, controlled by either the skeletal or cardiac troponin-tropomyosin complex, similar to the activation of fast-twitch muscle. (3) The absence of correlation between the divalent cation selectivity properties of actin heavy meromyosin ATPase controlled by cardiac troponin-tropomyosin and cardiac muscle tension or myofibrillar ATPase activation by Ca²⁺ and Sr²⁺ suggests that troponin, if primarily responsible for the activation of cardiac muscle, has very different in vivo and in vitro binding properties. (4) The close correlation between percentage of maximal Ca²⁺- and Sr²⁺-activated myofibrillar ATPase and tension in skinned fibers strongly justifies the use of myofibrillar ATPase, in contrast to a reconstituted troponin-tropomyosin actin heavy meromyosin ATPase system, as a biochemical measure of contraction.     

The effect of RGD fluorosurfactant polymer modification of ePTFE on endothelial cell adhesion, growth, and function.

We have synthesized and characterized a novel peptide fluorosurfactant polymer (PFSP) modification that facilitates the adhesion and growth of endothelial cells on expanded polytetrafluoroetheylene (ePTFE) vascular graft material. This PFSP consists of a poly(vinyl amine) (PVAm) backbone with integrin binding Arg-Gly-Asp (RGD) peptides and perfluorocarbon pendant branches for adsorption and stable adhesion to underlying ePTFE. Aqueous PFSP solution was used to modify the surface of fluorocarbon substrates. Following subconfluent seeding, endothelial cell (EC) adhesion and growth on PFSP was assessed by determining cell population at different time points. Spectroscopic results indicated successful synthesis of PFSP. PFSP modification of ePTFE reduced the receding water contact angle measurement from 120 degrees to 6 degrees , indicating successful surface modification. Quantification of cell population demonstrated reduced EC attachment efficiency but increased growth rate on RGD PFSP compared with fibronectin (FN). Actin staining revealed a well-developed cytoskeleton for ECs on RGD PFSP indicative of stable adhesion. Uptake of acetylated low-density lipoprotein and positive staining for VE-Cadherin confirm EC phenotype for adherent cells. Production of prostacyclin, a potent antiplatelet agent, was equivalent between ECs on FN and RGD PFSP surfaces. Our results indicate successful synthesis and surface modification with PFSP; this is a simple, quantitative, and effective approach to modifying ePTFE to encourage endothelial cell attachment, growth, and function.     

JM216-, JM118-, and cisplatin-induced cytotoxicity in relation to platinum-DNA adduct formation,glutathione levels and p53 status in human tumour cell lines with different sensitivities to cisplatin

The aim of this study is to establish anti-tumour potency of the new oral platinum drug JM216 and its metabolite JM118 in relation to the platinum (Pt)-DNA adduct formation, glutathione (GSH)-levels, and p53 status in human cancer cell lines with different sensitivities to cisplatin (CDDP). These parameters were studied in the CDDP sensitive human germ cell cancer cell line Tera and the small-cell lung cancer cell line GLC4 and their sublines with in vitro acquired CDDP resistance, Tera-CP and GLC4-CDDP, in a human ovarian cancer cell line transfected with mutant p53 (A2780/mt273) and with an empty vector as control (A2780/cmv), and in the intrinsic CDDP resistant human non-small-cell lung cancer cell line SW1573/S1 and colon carcinoma cell line Caco-2. Cytotoxicity was tested with the microculture tetrazolium (MTT)-assay. Pt-DNA adduct levels were assessed immunocytochemically. Quantitative analysis was performed by double fluorescence video microscopy. Results were correlated with GSH levels and p53 status of the cell lines. This study showed that both JM216 and JM118 can partially circumvent intrinsic and acquired resistance to CDDP. Drug-induced cytotoxicity only correlated negatively with GSH levels for JM216 and CDDP in the tested unselected cell lines. At equimolar basis, JM216 induced lower levels of Pt-DNA adducts in the various cell lines than JM118 and CDDP, whereas the JM118-induced amount and pattern of Pt-DNA adducts was comparable to CDDP. No difference in initial Pt-DNA adducts levels was observed between cell lines sensitive, acquired or intrinsic resistant to CDDP suggesting a Pt-resistance mechanism based on tolerance or increased repair, rather than decreased initial Pt-DNA adduct formation.     

Psychiatric disorders in a representative sample of incarcerated boys in the Netherlands

OBJECTIVE: To determine the prevalence of psychiatric disorders among incarcerated male adolescents and to investigate the influence of psychopathology on allocation to either plain detention or detention with compulsory treatment. METHOD: A cross-sectional study of a representative sample (N = 204) of incarcerated boys aged 12 to 18, using the Diagnostic Interview Schedule for Children (DISC). Data were collected from December 1998 to December 1999. RESULTS: Of the eligible subjects, 79% agreed to participate. Ninety percent reported at least one psychiatric disorder: disruptive behavior disorder 75% (95% confidence interval [CI]: 68-81%), substance use disorder 55% (95% CI: 48-63%), psychotic symptoms 34% (95% CI: 27-41%), ADHD 8% (95% CI: 5-13%), anxiety disorder 9% (95% CI: 6-15%), and affective disorder 6% (95% CI: 3-10%). After controlling for a broad range of sociodemographic characteristics and former treatment parameters, the presence of a psychiatric disorder was not associated with allocation to compulsory treatment. CONCLUSIONS: Compared with North American studies, relatively low rates of anxiety and affective disorders were found, probably due to the better availability of mental health services to disadvantaged youths with internalizing problems in the Netherlands. It should be examined whether standardized psychiatric assessments can improve the efficiency of allocation to detention programs with or without psychiatric treatment options.     

Growth differentiation factor 15 in patients with congenital dyserythropoietic anaemia (CDA) type II

Congenital dyserythropoietic anaemias (CDAs) are heterogeneous, hereditary disorders hallmarked by ineffective erythropoiesis and tissue iron overload. Growth differentiation factor 15 (GDF15) was suggested to mediate iron overload in iron-loading anaemias, such as the thalassaemias and CDAI by suppressing hepcidin, the key regulator of iron absorption. Here, we show that serum GDF15 concentrations are elevated in subjects with CDAI and CDAII. Despite similar disease characteristics, CDAI patients present with significantly higher GDF15 concentrations compared to CDAII patients. Hepcidin concentrations are inappropriately low in CDAII patients considering the severe hepatic iron overload associated with this disorder. GDF15 significantly correlates with the degree of anaemia (Hb), the response of erythropoiesis (reticulocyte index) as well as with iron availability in the serum (transferrin saturation). The observation that GDF15 is elevated in CDAII patients is consistent with the proposal that GDF15 is among the erythroid factors down-regulating hepcidin and contributing to iron overload in conditions of dyserythropoiesis.     

Low dietary iron intake restrains the intestinal inflammatory response and pathology of enteric infection by food‐borne bacterial pathogens

Orally administrated iron is suspected to increase susceptibility to enteric infections among children in infection endemic regions. Here we investigated the effect of dietary iron on the pathology and local immune responses in intestinal infection models. Mice were held on iron‐deficient, normal iron, or high iron diets and after 2 weeks they were orally challenged with the pathogen Citrobacter rodentium. Microbiome analysis by pyrosequencing revealed profound iron‐ and infection‐induced shifts in microbiota composition. Fecal levels of the innate defensive molecules and markers of inflammation lipocalin‐2 and calprotectin were not influenced by dietary iron intervention alone, but were markedly lower in mice on the iron‐deficient diet after infection. Next, mice on the iron‐deficient diet tended to gain more weight and to have a lower grade of colon pathology. Furthermore, survival of the nematode Caenorhabditis elegans infected with Salmonella enterica serovar Typhimurium was prolonged after iron deprivation. Together, these data show that iron limitation restricts disease pathology upon bacterial infection. However, our data also showed decreased intestinal inflammatory responses of mice fed on high iron diets. Thus additionally, our study indicates that the effects of iron on processes at the intestinal host–pathogen interface may highly depend on host iron status, immune status, and gut microbiota composition.     

Seed odor mediates an obligate ant-plant mutualism in Amazonian rainforests

Seed dispersal mutualisms are essential for the survival of diverse plant species and communities worldwide. Among invertebrates, only ants have a major role in seed dispersal, and thousands of plant species produce seeds specialized for ant dispersal in "diffuse" multispecies interactions. An outstanding but poorly understood ant-seed mutualism occurs in the Amazonian rainforest, where arboreal ants collect seeds of several epiphyte species and cultivate them in nutrient-rich nests, forming abundant and conspicuous hanging gardens known as ant-gardens (AGs). AG ants and plants are dominant members of lowland Amazonian ecosystems, and their interaction is both specific and obligate, but the means by which ants locate, recognize, and accept their mutualist seeds while rejecting other seeds is unknown. Here we address the chemical and behavioral basis of the AG interaction. We show that workers of the AG ant Camponotus femoratus are attracted to odorants emanating from seeds of the AG plant Peperomia macrostachya, and that chemical cues also elicit seed-carrying behavior. We identify five compounds from P. macrostachya seeds that, as a blend, attract C. femoratus workers. This report of attractive odorants from ant-dispersed seeds illustrates the intimacy and complexity of the AG mutualism and begins to illuminate the chemical basis of this important and enigmatic interaction.