Gene therapy targeting inflammation in atherosclerosis

The extensive cross-talk between the immune system and vasculature leading to the infiltration of immune cells into the vascular wall is a major step in atherogenesis. In this process, reactive oxygen species play a crucial role, by inducing the oxidation of LDL and the formation of foam cells, and by activating a number of redox-sensitive transcriptional factors such as nuclear factor kappa B (NFkappa B) or activating protein 1 (AP1), that regulate the expression of multiple pro/anti inflammatory genes involved in atherogenesis. Delivery of genes encoding antioxidant defense enzymes (e.g. superoxide dismutase, catalase, glutathione peroxidase or heme oxygenase- 1) or endothelial nitric oxide synthase (eNOS), suppress atherogenesis in animal models. Similarly, delivery of genes encoding regulators of redox sensitive transcriptional factors (e.g. NF-kappa B, AP-1, Nrf2 etc) or reactive oxygen species scavengers have been successfully used in experimental studies. Despite the promising results from basic science, the clinical applicability of these strategies has proven to be particularly challenging. Issues regarding the vectors used to deliver the genes (and the development of immune responses or other side effects) and the inability of sufficient and sustained local expression of these genes at the target-tissue are some of the main reasons preventing optimism regarding the use of these strategies at a clinical level. Therefore, although premature to discuss about effective "gene therapy" in atherosclerosis at a clinical level, gene delivery techniques opened new horizons in cardiovascular research, and the development of new vectors may allow their extensive use in clinical trials in the future

Intestinal Growth and Pathology og Giardia duodenalis assemblage subtype AI, AII, B end E in the gerbil model

This study investigated the significance of the genetic differences between assemblages A, B and E on intestinal growth and virulence. Intestinal growth and virulence were studied in 2 laboratory (AI: WB and B: GS/M-83-H7) and 6 field isolates of assemblage subtype AI, AII, B and EIII. Intestinal trophozoite burdens, body weight and faecal consistency were monitored until day 29 post-infection (p.i.), morphological (mucosal architecture and inflammation) and functional (disaccharidase and alkaline phosphatase enzyme activity) damage to the small intestine were evaluated on days 7 and 18 p.i. The assemblage subtypes AI and B were more infectious and produced higher trophozoite loads for a longer period compared to the subtypes AII and EIII. The body weight of infected gerbils was significantly reduced compared to uninfected controls, but did not differ between the assemblage subtypes. Consistent softening of the faeces was only observed with assemblage B. Assemblage B next to assemblage subtype AI elicited relatively higher pathogenicity, characterized by more extensive damage to mucosal architecture, decreased brush-border enzyme function and infiltration of inflammatory cells. Assemblage EIII and AII isolates showed relatively low virulence. The Giardia assemblage subtypes exhibit different levels of growth and virulence in the gerbil model

One single bout of low intensity isometric handgrip exercise reduces blood pressure during daily activities in healthy pre- and hypertensive individuals

To investigate the acute effect of one single session of isometric handgrip exercise (IHG) on blood pressure (BP) during daily life activities in healthy adults.status: publishe

Repairing trust between individuals and groups The effectiveness of apologies in interpersonal and intergroup contexts

Transgressions and injustice are an inevitable part of social life, both in interactions between individuals and between groups. But whereas interpersonal conflict between individuals typically impacts only few, intergroup conflict between groups can be harmful to many – as is illustrated by disputes between nations, political parties, and social groups. For this reason, it is crucial to understand how such transgressions can be restored. In interpersonal settings, there is considerable evidence that apologies can restore transgressions and enable victims and perpetrators to reconcile. But how does their remedial potential translate to disputes between groups? This question is not well understood. Indeed, victim groups frequently demand apologies from groups that wronged them. It is unknown, however, to what extent the remedial effectiveness of apologies in interpersonal disputes conflicts may translate to disputes conflicts between groups. The present research illuminates this question. In an experimental study (N = 272), we compared the effectiveness of apologies for restoring trust in after disputes transgressions between individuals or groups. We examined whether apologies restore trust as effectively in intergroup contexts as in interpersonal contexts. Moreover, we investigated how the remedial effectiveness of apologies depends on whether they are expressed in terms of primary (e.g., sadness and anger) or secondary emotions (e.g., guilt and disappointment). Method – Data were collected using a 2 (interaction type: interpersonal vs. intergroup) × 3 (response type: no apology vs. apology with primary emotions vs. apology with secondary emotions) between-subjects design. In the context of a social dilemma task, individuals or groups were wronged by the opposing individual or group. We measured to what extent trust in the other player (individual or group) was restored by the provision of either an apology with primary emotions or an apology with secondary emotions (compared to no apology). To test our predictions, we employed a mixed design, in which trust was measured at three moments (before the transgression, after the transgression, and after receiving an apology/no apology). Results – Results revealed that, in both in interpersonal and intergroup contexts, apologies significantly increased trust. However, their remedial impact was greater in interpersonal interactions (where they could fully restore trust to pre-transgression the levels prior to the transgressions) than in intergroup interactions (where they failed to fully restore trust). Furthermore, results indicated that the effectiveness of apology was shaped by its emotional content. Specifically, in disputes between individuals, only apologies with secondary emotions fully restored trust. Conversely, in disputes between groups, neither primary nor secondary emotions fully restored trust. This was explained by greater skepticism of apologies in intergroup contexts, particularly of those with secondary emotions. Discussion − The present findings suggest that apologies are less effective at restoring disputes in intergroup than interpersonal relations. Whereas apologies significantly increased trust in both contexts, apologies did not restore fully trust between groups following a transgression. This These findings underlines that intergroup interactions are more competitive and distrusting than interpersonal interactions between individuals, and suggests that more extensive remedies may be required to reduce intergroup tensions

Antimicrobial evaluation of the polyisoprenylated benzophenones nemorosone and guttiferone A

International audiencePolyisoprenylated benzophenones have been isolated from plants, particularly in the Clusiaceae family, and their biological properties have recently received considerable attention from a pharmacological point of view. The aim of the study was to investigate the polyisoprenylated benzophenones nemorosone and guttiferone A for their antimicrobial effect against a panel of bacteria, fungi and protozoan parasites. They showed a moderate activity against the Gram-positive bacterium Staphylococcus aureus, while no activity was demonstrated against Escherichia coli and the fungi Trichophyton rubrum and Candida albicans. An interesting activity was found for Plasmodium falciparum with IC50 values lower than 1 µM, while cytotoxicity on MRC-5 cells revealed CC50 values of 15.5 and 12.0 µM respectively for nemorosone and guttiferone A