Cardiovascular disease is one of the leading causes of death worldwide, and has been associated with many environmental risk factors. Recent evidence has indicated the involvement of pathogens such as viruses as causative agents, and specifically identified the coxsackievirus B serogroup as the leading culprit. Not only has coxsackievirus B3 (CB3) been identified from patients with cardiovascular disease, but also infection of mice with CB3 strains can reproduce human clinical heart disease in rodents. Several mechanisms have been proposed in an attempt to distinguish between pathology mediated by direct viral destruction of cardiac muscle cells or by the virus-induced immune response directed at infected myocytes or at 'mimicked' epitopes shared between viral and cardiac antigens. To distinguish between these mechanisms, we infected a unique mouse that diminishes the extent of infection and spread of the virus, but allows complete immunity to the virus. Transgenic mice expressing interferon-gamma in their pancreatic beta cells failed to develop CB-3-induced myocarditis. This work challenges the idea of the function of the immune response and 'molecular mimicry' in the CB-3-induced autoimmune myocarditis model, and instead favors the idea of virus-mediated damage. These results emphasize the benefit of reducing the level of viremia early during infection, thereby reducing the incidence of virus-mediated heart damage and autoimmunity.

The term acute aortic syndrome (AAS), coined several years ago, is now widely recognised. In the light of new findings in aortic pathology and in an era when modern imaging techniques are widely available and interventional management of AAS is increasing, some morphological and diagnostic aspects of acute aortic pathology have been examined and the syndrome updated. This article provides a new, comprehensive overview of the pathology, diagnosis, evolution and management of patients with AAS. As acute aortic disease is the most common fatal condition in patients with chest pain, prompt recognition and treatment is of paramount importance.

The function of natural killer T (NKT) cells in the immune system has yet to be determined. There is some evidence that their defect is associated with autoimmunity, but it is still unclear how they play a role in regulating the pathogenesis of T cell–mediated autoimmune diseases. It was originally proposed that NKT cells could control autoimmunity by shifting the cytokine profile of autoimmune T cells toward a protective T helper 2 cell (Th2) type. However, it is now clear that the major function of NKT cells in the immune system is not related to their interleukin (IL)-4 secretion. In fact, NKT cells mainly secrete interferon (IFN)-γ and, activated in the presence of IL-12, acquire a strong inflammatory phenotype and cytotoxic function.

Patients with IE who need urgent surgery have a poor clinical course. Heart failure, the main cause of urgent surgery, was not associated with higher mortality. However, persistent infection and renal failure were factors associated with higher post-surgical mortality.

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Gender-related differences in the brown adipose tissue (BAT) response to overfeeding rats on a cafeteria diet were studied by assessing the balance between the expression of beta-adrenoceptors (beta1-, beta2-, beta3-AR) and alpha2A-AR and their relation to the expression of uncoupling proteins (UCP1, UCP2, UCP3). Cafeteria diet feeding for 15 days, which involved a similar degree of hyperphagia in both sexes, led to a greater body weight excess in females than in males and a lower activation of thermogenesis. Gender-related differences were found for different adrenoceptor expression and protein levels, which might explain, in part, sex differences in the thermogenic parameters. The lower expression of alpha2A-AR in females than in males could be responsible for the higher expression of UCP1 and thermogenic capacity under non-hyperphagic conditions. However, in a situation of high adrenergic stimulation--as occurs with overfeeding--as there is a preferential recruitment of the beta3-AR by noradrenaline compared with other adrenergic receptors, the higher levels of beta3-AR in males rats than in females could be responsible for the greater thermogenic capacity and the lesser weight gain in males. Thus, the alpha2/beta3 balance in BAT could be a key in the thermogenic control.

The induction of autoimmunity by viruses has been attributed to numerous mechanisms. In mice, coxsackievirus B4 (CB4) induces insulin-dependent diabetes mellitus (IDDM) resembling the final step of disease progression in humans. The immune response following the viral insult clearly precipitates IDDM. However, the molecular pathway between viral infection and the subsequent activation of T cells specific for islet antigen has not been elucidated. These T cells could become activated through exposure to sequestered antigens released by damaged β cells, or they could have responded to factors secreted by the inflammatory response itself. To distinguish between these possibilities, we treated mice harboring a diabetogenic T cell repertoire with either the islet-damaging agent streptozotocin (STZ) or poly I:C, which nonspecifically activates T cells. Significantly, only treatment of mice with STZ resulted in IDDM and mimicked the effects observed following CB4 infection. Furthermore, antigen-presenting cells from STZ-treated mice were shown to directly activate autoreactive T cells and induce diabetes. Therefore, the primary role of CB4 in the precipitation of IDDM is to damage tissue, causing release and presentation of sequestered islet antigen. These events stimulate autoreactive T cells and thereby initiate disease.

objective: Studying the sex-dependent response of adiponectin and resistin adipose tissue expression and circulating levels in the onset of dietary obesity. Methods and Procedures: Male and female 4-week-old Wistar rats were fed a control or cafeteria (CAF) diet for 15 days. Body weight and energy intake were monitored. Gonadal (visceral), retroperitoneal (visceral) and inguinal (subcutaneous) white adipose tissue (WAT) depots were collected. Serum adiponectin and resistin and tissue mRNA levels were analyzed by western blot and reverse transcription-PCR, respectively. Serum levels of insulin, tumor necrosis factor-α (TNFα), and glucose were measured by enzyme-linked immunosorbent assay and by a glucose sensor. Insulin resistance was assessed by the homeostasis model assessment (HOMA). Results: Energy intake and adipose-tissue weight were significantly increased in the CAF rats, with higher increase in visceral than in subcutaneous fat, especially in females. The effective production of adiponectin and resistin (total levels adjusted per WAT weight) was decreased in the CAF groups, more markedly in females for adiponectin. This decrease was associated with the tendency to lower WAT mRNA levels for resistin, but not for adiponectin. Insulin levels were not significantly altered. Fasting glucose was slightly increased in CAF females. HOMA score was not significantly increased by CAF feeding, although it tended to be increased in a few CAF females. Discussion: Decrease of WAT adiponectin and resistin-effective production seems an early response to obesity development under a high-fat (CAF) diet, with sex-associated differences. This can probably be related to a physiological role of both adipokines modulating the insulin signaling system.