Mucin expression in peripheral airways of patients with chronic obstructive pulmonary disease

AIMS: To study the expression of mucins in peripheral airways in patients with chronic obstructive pulmonary disease (COPD). METHODS AND RESULTS: Peripheral lung sections from smokers with COPD (n = 9) and age-matched controls including smokers (n = 11) and lifelong non-smokers with normal lung function (n = 6) were stained with alcian blue, periodic acid-Schiff (PAS) and by immunohistochemistry of mucins (MUC): MUC2, MUC4, MUC5AC, MUC5B and MUC6. Histochemical staining and immunoreactivity of bronchiolar epithelium were graded and the presence or absence of stained mucus in the bronchiolar lumen was evaluated. There were no differences in alcian blue and PAS epithelial staining between the three groups. Intraluminal PAS staining was significantly more frequent among COPD subjects (P < 0.05). The expression of MUC5AC was significantly higher in the bronchiolar epithelium of patients with COPD (P < 0.05). Within the bronchiolar lumen, the predominant mucin was MUC5B. Intraluminal MUC5B was significantly more frequent among COPD patients (P < 0.05). CONCLUSIONS: COPD is specifically associated with increased expression of MUC5B in the bronchiolar lumen and of the mucin MUC5AC in the bronchiolar epithelium. These changes in mucin production in the peripheral airways may contribute to the pathophysiology of COPD.     

Aging increases basal but not stress-induced levels of corticosterone in the brain of the awake rat

The main purpose of this study was to evaluate the effect of aging on plasma and free corticosterone (CORT) levels in the brain in basal conditions and in response to an acute stressor. Microdialysis experiments were performed in the hippocampus (HC) and the prefrontal cortex (PFC) of young adult (6 months) and aged (24 months) male Wistar rats. Basal free levels of CORT in the HC and the PFC were higher in aged animals. Restraint stress increased plasma CORT and free CORT levels in the HC and the PFC both in young and aged animals. However, while the increase of plasma CORT was higher in aged rats compared with young rats, the increases of free CORT in the HC and the PFC were not different between these two groups of rats. These results suggest that the changes produced by aging in the brain may be related to the enhanced basal levels of free CORT and not to the CORT increases in response to stress.     

Management of Peritoneal Dialysis within a Home Care Program for Hematological Malignancies: Concerns and Perspectives Illustrated by a Case Report

The case of an 86-year-old man suffering from acute myeloid leukemia and end-stage renal disease, managed at home, with continuous peritoneal dialysis regimen, is described.     

Phase II study of the antiretroviral activity and safety of the glucocorticoid receptor antagonist mifepristone in HIV-1-infected patients

Preclinical studies have shown that the anti-glucocorticoid drug mifepristone effectively inhibits HIV replication both in vitro and in vivo. However, the drug did not demonstrate anti-HIV activity in a previous phase I/II study when administered at the daily dose of 75-225 mg. The aim of this study was to assess whether mifepristone may exert antiretroviral activity or influence immunological parameters when administered orally at daily doses of 150 or 300 mg in highly active antiretroviral therapy (HAART)-na?ve HIV-infected patients. We performed an open label non-randomized phase II study that included 26 patients who underwent 28 days of once daily oral administration of 150 (12 subjects) or 300 mg (14 subjects) of mifepristone. A total of 3 patients dropped out of the study, respectively 1 in the 150 mg dose group and 2 in the 300 mg dose group. The main hemato-chemical alterations reported were hypokalemia and increase in the blood levels of cortisol, especially in those patients that received mifepristone at the dose of 300 mg/day. Although we observed a trend of reduced viral load along the study in both groups, statistical significance was not achieved for either the primary nor the secondary endpoints. In summary, mifepristone treatment was well-tolerated but it failed to significantly influence viro-immunological parameters in HAART-na?ve HIV-infected patients.     

Necrotizing fasciitis: case reports and review of the literature

Necrotizing fasciitis is a rare, rapidly progressing infection affecting the superficial fascia and the subcutaneous tissue, accompanied by severe systemic toxicity and multiorgan failure. It is caused by aerobic and anaerobic bacteria, occasionally in a synergistic polymicrobial combination (Type I Necrotizing Fasciitis); in other cases group A -haemolitic Streptoccoccus is the organism responsible for the infection (Type II Necrotizing Fasciitis). The infection often originates from small traumatic injuries or operative wounds and rapidly spreads especially in individuals with identifiable risk factors or immunocompromised patients. Sometimes necrotizing fasciitis occurs when no known portal of entry for bacteria is present. The increasing incidence of necrotizing fasciitis observed may reflect a resurgence of highly virulent mutant strains of group A beta-haemolitic Streptococcus. The pathogenesis, clinical features and treatment of the disease have been reviewed in the light of recent literature. We also report clinical data for four patients with necrotizing fasciitis. They show the importance of early diagnosis and rapid, aggressive and radical surgical intervention. High-dose broad-spectrum antibiotic therapy and intensive medical support are also required to avoid a fatal outcome.     

Altered Signaling Lymphocytic Activation Molecule (SLAM) Expression in HIV Infection and Redirection of HIV-Specific Responses via SLAM Triggering

Signaling lymphocytic activation molecule (SLAM) is a transmembrane lymphocytic receptor which gets rapidly upregulated following cell activation. SLAM engagement augments T cell expansion and interferon-gamma (IFN-gamma) production independently of CD28. SLAM signaling is regulated by the SLAM-associated protein. We evaluated the expression and function of SLAM on CD4(+) and CD8(+) lymphocytes in HIV-infected individuals with either recently acquired infection (Group A) or asymptomatic HIV infection (Group B) and in healthy controls (HC). Soluble antigen (HIV env peptides and tetanus toxoid)- and mitogen-stimulated proliferation and IFN-gamma and IL-10 production upon SLAM costimulation were also measured. Results showed that: (1) SLAM-expressing CD4(+) and CD8(+) lymphocytes diminish in group A patients compared to both group B patients and HC; (2) SLAM expression on CD4(+) lymphocytes is preferentially associated with the lack of CD7 on cell surface (CD4(+)CD7(-) produce IL-10 but not IFN-gamma); (3) SLAM engagement increases HIV env peptide-stimulated, but neither tetanus toxoid- nor PHA-stimulated proliferation of peripheral blood mononuclear cells (PBMC) in patients but not in HC; and (4) SLAM engagement augments IFN-gamma and reduces IL-10 production by env peptide-stimulated PBMC of HIV-infected individuals. These results demonstrate that early HIV infection results in an altered SLAM expression which correlates with a time-limited impairment of cell-mediated immunity. Furthermore, they show that triggering via SLAM potentiates HIV-specific proliferative responses with simultaneous downregulation of IL-10 and redirection of the response to TH0/TH1.     

Mathematical models of passive motion at the human ankle joint by equivalent spatial parallel mechanisms

The paper presents a theoretical model of the ankle joint, i.e. tibio-talar articulation, which shows how the articular surfaces and the ligaments, acting together as a mechanism, can control the passive kinematics of the joint. The authors had previously shown that, in virtually unloaded conditions, the ankle behaves as a single degree-of-freedom system, and that two ligament fibres remain nearly isometric throughout the flexion arc. Two different equivalent spatial parallel mechanisms together with corresponding kinematic models were formulated. These assumed isometricity of fibres within the calcaneal-fibular and tibio-calcaneal ligaments and rigidity of the articulating surfaces, taken as three sphere-plane contacts in one model, and as a single spherical pair in the other. Geometry parameters for the models were obtained from three specimens. Motion predictions compare quite well with the measured motion of the specimens. The differences are accounted for by the simplifications adopted to represent the complex anatomical structures, and might be reduced by future more realistic representations of the natural articular surfaces.     

Podosomes are present in a postsynaptic apparatus and participate in its maturation

A critical step in synapse formation is the clustering of neurotransmitter receptors in the postsynaptic membrane, directly opposite the nerve terminal. At the neuromuscular junction, a widely studied model synapse, acetylcholine receptors (AChRs) initially aggregate to form an ovoid postsynaptic plaque. As the synapse matures, the plaque becomes perforated and is eventually transformed into a complex, branched structure. We found that this transformation also occurs in myotubes cultured in the absence of neurons, and used this system to seek machinery that orchestrates postsynaptic maturation. We show that perforations in the AChR aggregate bear structures resembling podosomes, dynamic actin-rich adhesive organelles involved in matrix remodeling in non-neuronal cells but not described in neural structures. The location and dynamics of synaptic podosomes are spatiotemporally correlated with changes in AChR aggregate topology, and pharmacological disruption of podosomes leads to rapid alterations in AChR organization. Our results indicate that synaptic podosomes play critical roles in maturation of the postsynaptic membrane.