Role of lysophosphatidic acid receptor LPA2 in the development of allergic airway inflammation in a murine model of asthma

<p>Abstract</p> <p>Background</p> <p>Lysophosphatidic acid (LPA) plays a critical role in airway inflammation through G protein-coupled LPA receptors (LPA_1-3). We have demonstrated that LPA induced cytokine and lipid mediator release in human bronchial epithelial cells. Here we provide evidence for the role of LPA and LPA receptors in Th2-dominant airway inflammation.</p> <p>Methods</p> <p/> <p>Wild type, LPA₁heterozygous knockout mice (LPA₁^+/-), and LPA₂heterozygous knockout mice (LPA₂^+/-) were sensitized with inactivated <it>Schistosoma mansoni </it>eggs and local antigenic challenge with <it>Schistosoma mansoni </it>soluble egg Ag (SEA) in the lungs. Bronchoalveolar larvage (BAL) fluids and lung tissues were collected for analysis of inflammatory responses. Further, tracheal epithelial cells were isolated and challenged with LPA.</p> <p>Results</p> <p>BAL fluids from <it>Schistosoma mansoni </it>egg-sensitized and challenged wild type mice (4 days of challenge) showed increase of LPA level (~2.8 fold), compared to control mice. LPA₂^+/-mice, but not LPA₁^+/-mice, exposed to <it>Schistosoma mansoni </it>egg revealed significantly reduced cell numbers and eosinophils in BAL fluids, compared to challenged wild type mice. Both LPA₂^+/-and LPA₁^+/-mice showed decreases in bronchial goblet cells. LPA₂^+/-mice, but not LPA₁^+/-mice showed the decreases in prostaglandin E2 (PGE2) and LPA levels in BAL fluids after SEA challenge. The PGE2 production by LPA was reduced in isolated tracheal epithelial cells from LPA₂^+/-mice. These results suggest that LPA and LPA receptors are involved in <it>Schistosoma mansoni </it>egg-mediated inflammation and further studies are proposed to understand the role of LPA and LPA receptors in the inflammatory process.</p

Human Immunodeficiency Virus Envelope Protein Gp120 Induces Proliferation but Not Apoptosis in Osteoblasts at Physiologic Concentrations

Patients with HIV infection have decreased numbers of osteoblasts, decreased bone mineral density and increased risk of fracture compared to uninfected patients; however, the molecular mechanisms behind these associations remain unclear. We questioned whether Gp120, a component of the envelope protein of HIV capable of inducing apoptosis in many cell types, is able to induce cell death in bone-forming osteoblasts. We show that treatment of immortalized osteoblast-like cells and primary human osteoblasts with exogenous Gp120 in vitro at physiologic concentrations does not result in apoptosis. Instead, in the osteoblast-like U2OS cell line, cells expressing CXCR4, a receptor for Gp120, had increased proliferation when treated with Gp120 compared to control (P<0.05), which was inhibited by pretreatment with a CXCR4 inhibitor and a G-protein inhibitor. This suggests that Gp120 is not an inducer of apoptosis in human osteoblasts and likely does not directly contribute to osteoporosis in infected patients by this mechanism

Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation

Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases

Construction of the new lock in Terneuzen using pneumatic caissons

The lock complex at Terneuzen is the main entrance for ships coming from the Westerscheld and navigating towards the cities of Terneuzen and Ghent. The construction of a new large lock at the lock complex of Terneuzen is planned to increase its capacity. This lock will be built between the existing locks. The ground level is situated at NAP +6 meter. The minimum normative sea water level occurring twice a year is NAP -2.85 meter. The new lock will have larger dimensions than the current locks. It is assumed that a ship with a draft of 13.1 meter must be able to use the lock tide independently. Because of the large allowable draft the lock must be founded to a depth of NAP -17.26 m. It is becoming increasingly difficult to construct the new lock with traditional building methods like combi– or diaphragm walls to such extent. In this master thesis the use of pneumatic caissons as alternative construction method for the new lock in Terneuzen has been elaborated. Pneumatic caissons have been used for many times as construction method. However, pneumatic caissons have never been used with the dimensions required for the new lock head. (l = 132m, w = 45m & h = 33m) The pneumatic caisson method involves the construction of a relative rigid concrete box at ground level that is lowered into the ground by excavating the soil underneath it. Under the bottom slab of a pneumatic caisson an air-pressurized space, called the working chamber, is present which is made up of tapering walls around the perimeter of the caisson base slab. These tapering walls are called the cutting edges of the caisson. The working chamber is kept dry by the presence of air pressure. Due to the air pressure, groundwater is not able to enter the working chamber. The deeper the caisson is located below the water table, the higher the air pressure should be. In this master thesis two construction alternatives for the lock heads with help of pneumatic caissons are elaborated: 1. The construction of one large pneumatic caisson with a length of 132 meter, width of 45 meter and a height of 33 meter containing the complete lock head including the gate chamber and gate recess. The working chamber is divided into 14 compartments. 2. The construction of two (compartmentalized–) pneumatic caissons which can be subsided independently. One caisson with a length of 10 meter, width of 45 meter and a height of 33 meter is covering the gate recess and the other caisson with a length of 67 meter, width of 45 meter and a height of 33 meter is covering the gate chamber. Between the pneumatic caisson an immersible caisson is located. This caisson acts as foundation for the guiding rail and moving equipment and prevents piping below the lock gates. With help of SCIA Engineer, a software package for structural calculations, the structural feasibility of the caisson is analysed and worked out. Due to the lack of bending and torsional stiffness in the first construction alternative the occurring forces and moments are up to 2 times larger in comparison to the second construction alternative. The use of pneumatic caissons to construct the lock head has some advantages over the use of a traditional building pit. The building time of 22 months is 8 months shorter in duration compared with the building pit and the building costs are with respectively Euro 48.300.000 and Euro 37.700.000 much lower than the building costs of a building pit which is estimated at Euro 52.600.000. Moreover the pneumatic caissons can be constructed in controlled conditions above the surface level. Despite of the advantages the construction method has a large number of disadvantages. Different conclusions can be drawn up. Some conclusions are in favor of the construction with pneumatic caisson. On the other hand the construction method has some important disadvantages that can not be neglected. A considerably large working space is required for the sedimentation basin and bentonite de-sanding installation during subsidence of the caisson(s). The possibility of rotation of the caisson during subsidence and working under an overpressure increase the associated risks. It should be taken into account that about 50% of the surface area of the bottom slab must be reinforced against shear. Also a large amount of bending reinforcement (101 kg=m3–219 kg=m3) is required. Moreover there is less practical experience with the construction of pneumatic caissons. A comparison between the options on feasibility, safety, risk, required materials, building time and costs shows that the reference design, the use of a traditional building pit to construct the lock head, is the best conceivable option.Hydraulic EngineeringCivil Engineering and Geoscience

Physical and mental health of the aged in Eindhoven, 1986

Epidemiological investigation into the health of people between 65 and 75 years in the Dutch municipality of Eindhoven in support of the municipal policy towards the elderly. The questionnaire was made up of a combination of existing measuring instruments: BIOPRO (Diekstra/Hosman-1983)/ Loneliness scale (De Jong-Gierveld/Kamphuis-1983)/ Muenchener Alcohol Test (Feurelein/Walberg/Van Limbeek- 1985/ Neuroses and social environment scale (Henderson-1984)/ Symptom checklist (Derogatis/Arrindell/Ettema-1981)/ Scale for subjective well-being of elderly (Tempelman/Tellegen-1984)/ Social desirability scale (Crowne/Marlow) / health / insurance / general practitioner / illness / symptoms / medical complaints / hospital / fear / depression / irritation / nervousness / medicine / drugs / use of alcohol / problems / coping behaviour / life events / knowledge of institutions for medical, mental, social help / self support ability / social contacts. Background variables: basic characteristics/ place of birth/ housing situation/ household characteristics/ occupation/employment/ income/capital assets/ education/ religio