Enhancement of learning and memory after activation of cerebral Rho GTPases

The mechanism whereby the morphology and connectivity of the dendritic tree is regulated depends on an actin dynamics that, in turn, is controlled by Rho GTPases, a family of small GTP-binding proteins encompassing Rho, Rac, and Cdc42 subfamilies. Cytotoxic necrotizing factor 1 (CNF1), a protein toxin from Escherichia coli, constitutively activates Rho GTPases, thus leading to remodeling of the actin cytoskeleton in intact cells. Here, we show that the modulation of cerebral RhoA and Rac1 activity induced by CNF1 in mice leads to (i) rearrangement of cerebral actin cytoskeleton, (ii) enhanced neurotransmission and synaptic plasticity, and (iii) improved learning and memory in various behavioral tasks. The effects persist for weeks and are not observed in mice treated with a recombinant CNF1, in which the enzymatic activity was abolished by substituting serine to cysteine at position 866. The results suggest that learning ability can be improved through pharmacological manipulation of neural connectivity.     

Age and target organ damage in essential hypertension: role of the metabolic syndrome

OBJECTIVE: We sought to investigate the association of the metabolic syndrome (MS) with cardiovascular alterations in essential hypertensives in relation to age. METHODS: A total of 3266 untreated and treated hypertensive patients categorized in three age groups (I: 17 to 40 years; II: 41 to 64 years; III: >64 years) were considered for this analysis. All patients underwent extensive investigations searching for target organ damage (TOD). The MS was defined according to Advanced Technology Laboratories (ATP) III criteria. RESULTS: In the entire population, the risk of left ventricular hypertrophy (LVH), carotid abnormalities, and microalbuminuria increased by 2.5 (P = .003), 2.2 (P = .005), and 1.5 times (P = .01), respectively, in the presence of MS after adjusting for several confounders. Prevalence of LVH (group I: 39% v 22%; group II: 53% v 35%; group III: 69% v 52%, P < .01 for all), carotid thickening (group I: 8% v 2%; group II 29% v 19%; group III: 69% v 52%, P < .05 for all) and microalbuminuria (group I: 20% v 11%; group II: 16% v 8%; group III: 18% v 11%, P 相似文献   

Relationship of coping styles with quality of life and depressive symptoms in older heart failure patients

This study examines the relationship between coping styles, quality of life, and depressive symptoms in older heart failure patients. Eighty heart failure patients seeking treatment in an outpatient heart failure or family practice clinic participated in a study examining depression, disability, and heart failure. Patients completed a clinical interview and questionnaires about mood, functional impairment, comorbid illness, quality of life, and coping. Heart failure severity and maladaptive coping styles, including denial, self-distraction, and self-blame, negatively affected quality of life and depressive symptoms. The use of maladaptive coping strategies involves efforts that divert attention from the illness and suggests the need to provide heart failure patients the skills to directly address the stress associated with their illness. Interventions that target these coping strategies may help patients take a more active role in their heart failure management and may improve psychological and cardiac outcomes.     

Fatal disseminated toxoplasmosis during primary HIV infection

Toxoplasmosis is a well recognized manifestation of AIDS, but the disseminated disease is a rare condition and it has not been associated to HIV seroconversion to our knowledge. We describe a fatal episode of disseminated T. gondii acute infection with massive organ involvement during primary HIV infection. The serological data demonstrate primary T. gondii infection. The avidity index for HIV antibodies supports recent HIV-1 infection.     

Cross-sectional epidemiological study to evaluate the cardiovascular profile of a cohort of blood donors

Background

Cardiovascular diseases are among the most frequent causes of mortality and morbidity in industrialised countries. The identification of subjects at high risk of cardiovascular diseases is one of the main aims of individual primary prevention programmes and is the essential background for instituting interventions aimed at reducing modifiable risk factors, from lifestyle changes to pharmacological interventions.

Donors and method

In order to evaluate the absolute global risk of cardiovascular disease in the population of blood donors of the Transfusion and Immunohaematology Centre of the Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena of Milan, we used the absolute global cardiovascular risk (CVR) score of the Progetto Cuore.Between September 2004 and June 2006, 11,093 blood donors were evaluated for their suitability for donating blood. The criteria for inclusion in the calculation of the individual values of the absolute global CVR score were: age between 35 and 65 years old, fasted for at least 12 hours, and no previous reported or diagnosed cardiovascular episodes. Each donor was also asked to provide written informed consent to participation in the study.The population of blood donors was divided into four groups according to their CVR score: CVR < 3%, CVR between 3% and 10%, CVR between 10% and 20%; CVR above 20%. The characteristics of the population were analysed subdividing the subjects according to age and gender.

Results

Although most of the blood donors belonged to the group with low CVR, it was nevertheless possible to identify a group of donors with high CVR.

Conclusions

It is to be hoped that CVR is calculated ever more widely in the population of blood donors in order to identify individuals at high CVR and also with the aim of reducing the levels of risk factors in the population with low or moderate CVR.     

Adult-onset Still's disease: can recent advances in our understanding of its pathogenesis lead to targeted therapy?

Adult-onset Still's disease is a rare systemic inflammatory disease of unknown etiology, characterized by daily high, spiking fevers, evanescent rash, and arthritis. There is no single diagnostic test for adult-onset Still's disease; rather, the diagnosis is based on clinical criteria and necessitates the exclusion of infectious, neoplastic, and other 'autoimmune' diseases. Proinflammatory cytokines such as interleukin (IL)-1, IL-6, and IL-18, interferon-gamma, tumor necrosis factor, and macrophage colony-stimulating factor are elevated in patients with adult-onset Still's disease and are thought to have a major role in the pathogenesis of the disease. Treatment consists of nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressants (methotrexate, gold, azathioprine, leflunomide, cyclosporin, and cyclophosphamide), intravenous immunoglobulin, and cytokine (tumor necrosis factor, IL-1 and IL-6) inhibitors. Recent advances in basic immunology have enhanced our ability to hinder the pathogenic mechanisms associated with adult-onset Still's disease and have led to a paradigm shift where targeted treatments have an increasingly important role.     

Effects of stress and neuropeptides on airway responses in ovalbumin-sensitized rats

OBJECTIVE: The aim of this study was to investigate the influence of stress and neuropeptides on airway responses in ovalbumin (OVA)-sensitized rats. METHODS: Three experimental conditions were employed: neonatal capsaicin treatment, foot shock stress and OVA sensitization. For neuropeptide depletion, male Wistar rats were neonatally treated with capsaicin (50 mg/kg) or with control solution 2 days after birth. Ninety days later, they were injected with OVA and aluminum hydroxide (ED0) or no injection. Thereafter, rats of the stressed groups were individually placed in a shuttle box where they received 50 mild escapable foot shocks/day; the stressful stimuli were repeated until ED14, when the animals received OVA aerosol. Pulmonary mechanic function was measured before and after OVA challenge in anesthetized and mechanically ventilated rats. RESULTS: Data on ultrasonic vocalizations and corticosterone showed high levels of anxiety in stressed animals. As expected, a significant increment in airway elastance and resistance after the OVA challenge was found in sensitized rats compared to non-sensitized ones. Capsaicin treatment decreased the values of elastance in sensitized and non-stressed rats; however, after the OVA challenge, elastance was increased in stressed animals. No differences were found in the levels of resistance among sensitized and non-stressed rats; however, a reduced increment in resistance was verified in capsaicin-treated, stressed animals. CONCLUSIONS: Our results suggest that neurokinin depletion and stress may affect smooth muscle tonus around the airways during an anaphylactic reaction. These data suggest that stress and neuropeptides play a significant role in pulmonary function in OVA-sensitized rats.