Rapid leukocyte integrin activation by chemokines

Summary: Chemokines control selective targeting of circulating leukocytes to the microvasculature by triggering inside-out signal transduction pathways leading to integrin-dependent adhesion. Integrin activation by chemokines is very rapid, is downmodulated within minutes and appears to involve both enhanced heterodimer lateral mobility on the plasma membrane, facilitating encounters with dispersed ligand, as well as induction of a high-affinity state. These two modalities of integrin activation by chemokines involve distinct signaling pathways in the cell, yet complement each other functionally, allowing binding of rolling cells under conditions of low as well as high ligand density. Recent data show that chemokines generate both pro- and anti-adhesive intracellular signaling events, whose equilibrium is likely to be relevant to the kinetics of adhesion and de-adhesion, and to cell movement during diapedesis and chemotaxis. Importantly, chemokines utilize different signaling mechanisms to modulate the activity of distinct integrin subtypes. These recent advances suggest that chemokines may regulate adhesive responses of immune cells based not only on patterns of chemokine receptor expression, but also on variable signaling pathways that can modulate the pro-adhesive responses of leukocytes as a function of their differentiated state, and of the local microenvironment.     

MEG Characterization of Spontaneous Alpha Rhythm in the Human Brain

The present piece of research studied the spontaneous alpha rhythm of the human brain by combining the use of a whole-cortex neuromagnetometer and Magnetic Resonance Imaging. Single trials of spontaneous brain activity were recorded from ten human subjects asked to rest, with their eyes either closed or open, in relaxed wakefulness. MEG measurements were conducted over a period of one and a half years. The replicability of the results was confirmed for eight subjects out of ten. For three subjects, the alpha rhythm did not show any reductions due to the opening of the eyes. Both field map pattern and location of the estimated source were persistently stationary during each of the bursts of oscillations of the alpha rhythm. Dipoles were concentrated in clusters, indicating the existence of several spatially distributed sources. The calcarine fissure, the parieto-occipital sulcus and the surrounding occipital and parieto-occipital areas were identified as cortical sites of the brain where the alpha rhythm may originate. For four subjects, the majority of the sources were located near or in the calcarine fissure, while for five subjects, they were located near or in the parieto-occipital sulcus and for the remaining subject they were equally divided between the two generation sites.     

Peripheral cytokine release in Alzheimer patients: correlation with disease severity

Various studies suggested that inflammation is involved in the pathogenesis of Alzheimer's disease (AD). We investigated cytokine release from LPS-stimulated blood cells of 32 AD patients, with different disease severity, compared to 16 age-related controls. A significant decrease of IL-1beta and IL-6 secretion was observed in severely demented patients; TNF-alpha release was also decreased, but not significantly. By contrast, mild and moderate patients showed a cytokine release similar to controls. IL-1beta, IL-6 and TNF-alpha secretion was negatively correlated with the severity of dementia, quantified by the MMSE. Our data suggest that alterations of the immune profile are associated with AD progression.     

Relative growth of adenomatous polyps of the colon

Summary The volume of the adenomatous mucosa (V), the area of the surface epithelium (Ss), the area of the glandular epithelium (Sg), and theSg:Ss ratio were calculated in a series of 14 adenomatous polyps (APs) of a case of multiple polyposis of the colon. The equation of simple allometry was used to study the relative growth of the four series of values.Ss grew isometrically with size;Sg overgrewSs and accounted for most of the increase inV. TheSg:Ss ratio increased withSg andV.     

Comparison of intranasal and transdermal estradiol on nasal mucosa in postmenopausal women

OBJECTIVE: To compare nasal symptomatology and function and local concentrations of estradiol (E2), estradiol receptor (ERalpha), vasoactive intestinal peptide (VIP), substance P (SP) and neuropeptide Y (NPY) in nasal biopsies of 20 postmenopausal women complaining of paradoxical nasal stuffiness before and after treatment with intranasal or transdermal E2. DESIGN: Twenty healthy postmenopausal women willing to start hormone therapy (HT) were allocated to one of two groups, using a computer-generated randomization list.Ten postmenopausal women were treated with transdermal 17beta-estradiol 50 microg daily plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group A). Ten postmenopausal women were treated with intranasal 17beta-estradiol 300 microg/day (one spray delivery of 150 microg per nostril) plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group B). Fourteen fertile women undergoing nasal mucosa biopsy during plastic surgery were used as controls for the immunohistochemical evaluation (Group C).All women in groups A and B underwent evaluation of nasal stuffiness score, mucociliary transport time, rhinoscopy, and active anterior rhinomanometry at the beginning of the study and after, VIP, SP, and 6 months of HT. Nasal biopsies and evaluation of local concentrations of E2, ERalpha NPY were performed in groups A and B before and after 6 months of HT and in group C. RESULTS: Both intranasal and transdermal HT improve nasal symptomatology and nasal mucosa appearance and reduce mean mucociliary transport time. The effectiveness of intranasally administered therapy at improving nasal function is significantly better than transdermal therapy. In comparison with premenopausal controls, untreated postmenopausal women of group A and B showed significantly decreased immunopositivity for E2, ERalpha, and SP. HT induced a significant increase in E2, ERalpha, VIP, and SP and a decrease in NPY immunopositivity. Intranasal therapy was associated with a significantly higher immunopositivity for VIP and SP. CONCLUSIONS: HT improves nasal function and symptomatology in postmenopausal women with paradoxical nasal stuffiness, modulating nasal mucosa function through an action on cholinergic, adrenergic, and sensory peptides. Intranasally administered HT is more effective at improving nasal function than transdermal HT.     

Viral determinants and host immune responses in the pathogenesis of HBV infection

Hepatitis B virus (HBV) is a virus that infects about 350,000,000 people worldwide with a clinical spectrum of acute hepatitis, the healthy carrier state, cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is the result of complicated viral-host interactions. As in other infections with non-cythopatic viruses, the immune response is thought to play a crucial role in disease pathogenesis but there is increasing evidence that a variety of viral mechanisms, some depending on the function of virally encoded proteins, have a profound impact on the infected hepatocytes, the liver microenvironment, and host anti-viral responses. Indeed, the virus has evolved multiple mechanisms to ensure its success in infecting a susceptible host. The essential aspects of the life cycle of HBV and the host immune response are reviewed and recent new developments in the molecular virology of HBV, including experimental animal models, in the role of accessory viral proteins in disease pathogenesis and HCC development and in the characterisation of the T cell response in the control of HBV infection, are highlighted.     

Inhibition of diamine oxidase by antihistaminic agents and related drugs

Various drugs were tested as inhibitors of diamine oxidase on the basis of chemical relationships to the enzyme substrates.It was found that serotonine tryptamine and phenformin are good competitive inhibitors while cimetidine and pheniprazine are non-competitive inhibitors. Other antihistaminic drugs like promethazine are less powerful inhibitors.