Acute lung inflammation induced in the rabbit by local instillation of 1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine or of native platelet-activating factor.

The intratracheal instillation into rabbits of 1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC) or native platelet-activating factor (PAF) was shown to induce a dose-dependent acute pulmonary inflammation characterized by accumulation of macrophages in the alveolar space, degenerative and necrotic changes of alveolar epithelium, and accumulation of polymorphonuclear leukocytes (PMNs) and platelets in the alveolar capillary lumens with degenerative changes of endothelial cells. Infiltration of alveolar septa by inflammatory cells and, in a later stage, pulmonary fibrosis were also observed. Intrabronchial instillation of lysoglyceryl ether phosphorylcholine (lyso-GEPC) produced no inflammatory changes or only mild ones. In comparison with acute inflammation induced by intratracheal instillation of C5a des Arg, which is mainly characterized by the presence of neutrophils, red blood cells, and fibrin in the alveolar space, AGEPC and native PAF seem to induce a more severe accumulation of macrophages in the alveolar space and septa and of platelet and PMNs in the lumens of alveolar capillaries. These results are compatible with the concept that during inflammatory reaction an intraalveolar release of PAF contributes to the development of pulmonary injury.     

Circulating immune complexes and kidney lesions following 131I administration in mice with thyroglobulin antibodies

Immune complexes containing thyroglobulin have been described in kidneys of some patients with thyroid disease. We investigated the circulating immune complexes (with the Raji cell radioassay) and the kidney histopathology (by immunofluorescence and electron microscopy) in mice that received radioiodine to release thyroglobulin in the circulation, 2 or 4 weeks after immunization with mouse thyroglobulin in Freund's complete adjuvant. Circulating immune complexes and thyroglobulin, antibodies were found in all mice. Granular deposition of IgG, IgM, C3, and thyroglobulin, mainly in the mesangium but also in the capillary walls of the glomeruli, were observed in most of the mice. These experiments suggest that circulating immune complexes composed of thyroglobulin are responsible for the glomerular lesions. Hyperthyroid patients should be tested for thyroglobulin antibodies before treatment with radioiodine to avoid formation of thyroglobulin-containing circulating immune complexes.     

Sedation in palliative care - a critical analysis of 7 years experience

BACKGROUND: The administration of sedatives in terminally ill patients becomes an increasingly feasible medical option in end-of-life care. However, sedation for intractable distress has raised considerable medical and ethical concerns. In our study we provide a critical analysis of seven years experience with the application of sedation in the final phase of life in our palliative care unit. METHODS: Medical records of 548 patients, who died in the Palliative Care Unit of GK Havelhoehe between 1995-2002, were retrospectively analysed with regard to sedation in the last 48 hrs of life. The parameters of investigation included indication, choice and kind of sedation, prevalence of intolerable symptoms, patients' requests for sedation, state of consciousness and communication abilities during sedation. Critical evaluation included a comparison of the period between 1995-1999 and 2000-2002. RESULTS: 14.6% (n = 80) of the patients in palliative care had sedation given by the intravenous route in the last 48 hrs of their life according to internal guidelines. The annual frequency to apply sedation increased continuously from 7% in 1995 to 19% in 2002. Main indications shifted from refractory control of physical symptoms (dyspnoea, gastrointestinal, pain, bleeding and agitated delirium) to more psychological distress (panic-stricken fear, severe depression, refractory insomnia and other forms of affective decompensation). Patients' and relatives' requests for sedation in the final phase were significantly more frequent during the period 2000-2002. CONCLUSION: Sedation in the terminal or final phase of life plays an increasing role in the management of intractable physical and psychological distress. Ethical concerns are raised by patients' requests and needs on the one hand, and the physicians' self-understanding on the other hand. Hence, ethically acceptable criteria and guidelines for the decision making are needed with special regard to the nature of refractory and intolerable symptoms, patients' informed consent and personal needs, the goals and aims of medical sedation in end-of-life care.     

Release of O2- and LTC4 by murine eosinophils: role of intra- and extracellular calcium.

Using an experimental model of mouse peritoneal eosinophilia, we investigated the role of Ca2+ in the in vitro activation of these cells challenged with specific Mesocestoides corti antigen. We have detected LTC4, a metabolite derived from arachidonic acid by way of 5'lipo-oxygenase and superoxide anion from the oxidative burst, as inflammatory mediators produced by activated eosinophils. Preincubation with hyperimmune mice serum increases the amount of LTC4 and superoxide anion in response to the antigenic extract. Release of O2- is inhibited by Verapamil (a voltage-gated calcium channel) and Quin 2 (an intracellular trapped chelator of calcium). Also, LTC4 produced by preincubated eosinophils challenged with M. corti is dramatically inhibited by Quin 2. Our results suggest an intact mechanism for calcium control for the release of these inflammatory mediators by eosinophils, after specific antigenic stimulation.     

Titanium-porcelain system. Part III: effects of surface modification on bond strengths

During its development, titanium was found to be incompatible with conventional dental porcelains due to weak bond strength brought about by titanium's high yet oxidative nature. In spite of the development of new low-fusing porcelains designed for titanium application, previous studies have shown that sandblasting pre-treatment prior to porcelain application led to weakening of the metal-ceramic bonding. The aim of this study is to search for an effective alternative to sandblasting for the surface treatment of the titanium substrate in the titanium-porcelain system. The research evaluated the bond strength of 165 samples of titanium-porcelain systems divided into 11 groups. A three-point flexural bend test was conducted to measure the force required to fracture the porcelain on the titanium substrate. A correlation between the type of surface treatment and the bond strengths of each group was evaluated if it resulted to significant differences. The study found significantly differences in the energy-to-break of titanium-porcelain systems treated with hydrochloric acid and sandblasting compared with the control group. The bonds strength achieved by the titanium-porcelain system when treated with hydrochloric acid is comparable to that of conventional metal-ceramic alloy system. Hydrochloric acid treatment of the titanium substrate is a promising alternative to sandblasting for the surface treatment of the titanium substrate in the titanium-porcelain system.     

Mechanical properties of four methylmethacrylate-based resins for provisional fixed restorations

The use of a provisional restoration is an important phase in the treatment of the dental prosthetic patient. A good provisional restoration should satisfy the following requirements: pulpal protection, positional stability, ease in cleaning, accurate margins, wear resistance, dimensional stability, and serve as a diagnostic aid in treatment assessment and esthetics. There is a tendency for discoloration, occlusal wear, and fracture that eventually leads to unnecessary repair. Heat-processed and reinforced methacrylate-based resins have been used to improve the mechanical and physical properties of provisional restorations. Among various improvements, the interpenetrating network crosslinked PMMA (IPN) has been shown to have superior mechanical properties if manufactured through a dough compression molding process at 130 degrees C. However, there have been no published data that relate with the use of this material for fixed provisional restorations.The objective of this study was to compare four methyl methacrylate-based resins for provisional crowns and bridges with varying processing cycles, including JET [self-cure], ACRALON [heat-cured], titanium dioxide filled PMMA [heat-cured], and IPN [heat-cured denture tooth resin]. Properties studied included transverse strength, toughness, rigidity, and hardness. From the results of this study the following conclusions can be made: the IPN group may have had a lower degree of conversion as demonstrated by decreased strength, toughness, and hardness data as compared with Acralon. Increasing the polymerization cycle of unmodified Acralon resin causes a significant increase in strength.     

The role of COX-2 in angiogenesis and rheumatoid arthritis

Recent evidence suggests that cyclooxygenase (COX)-2 is a mediator of angiogenesis, and COX-2 activity is known to be upregulated in the rheumatoid arthritis (RA) synovium. We examined whether mediation of angiogenesis by COX-2 was occuring in cells of the RA synovium and in microvascular endothelial cells (ECs) that are similar to those found in the RA synovium. We demonstrate that rofecoxib, a selective COX-2 inhibitor, acts directly on human dermal microvascular ECs (HMVECs) to inhibit their chemotactic and tube forming ability. Likewise, pretreatment of HMVECs with rofecoxib significantly inhibited their ability to form tubes induced by conditioned media (CM) of activated RA synovial fibroblasts. When RA synovial fibroblasts were pretreated with rofecoxib for 16 h and then stimulated with interleukin (IL)-1beta, their CM induced significantly less HMVEC tube formation when compared with CM from vehicle-treated RA synovial fibroblasts. ELISAs performed on activated RA fibroblast CM for known proangiogenic factors demonstrated a significant reduction in bFGF, in addition to the expected decrease in PGE(2). Our studies suggest that COX-2-induced angiogenic activity is an active mechanism within diseased synovium and may provide an additional rationale for the use of COX-2 inhibitors in RA.     

Detection of two forms of GP330. Their role in Heymann nephritis.

Heymann nephritis is characterized by glomerular immune deposits that contain a glycoprotein called gp330. The deposits are believed to result from shedding of immune complexes formed on podocytes. Complexes are also shed from proximal tubule cells, when antibodies combine with gp330 on the cell surface. We performed the present study to investigate what portion of the gp330 molecule is shed, using a rabbit antiserum against a peptide deduced to be in the cytoplasmic domain of gp330, as well as a rabbit antiserum and two monoclonal antibodies that recognize extracellular epitopes of gp330. The anti-cytoplasmic peptide antiserum precipitated from Fx1A (a crude renal cortical membrane preparation), a protein with a mass of about 440 kd that was reactive with two monoclonal anti-gp330 antibodies. (In our experiments, the protein called gp330 generally has a mass estimated to be about 440 kd.) The anti-cytoplasmic peptide antiserum also reacted with a truncated gp330 protein produced in transfected COS cells. Immunohistochemical studies showed that all the antibodies recognized the same group of epithelial cells. However, as seen in immunoultrastructural studies of proximal tubules, the anti-cytoplasmic peptide antiserum reacted only with components at the base of microvilli, whereas the anti-gp330 ectodomain antibodies identified material not only at the base, but over the surface of microvilli as well. In rats with Heymann nephritis, glomerular deposits and material shed into tubule lumens reacted with antibodies against extracellular epitopes of gp330, but not with the anti-cytoplasmic peptide antiserum. We propose that there are two forms of gp330 on the cell surface of proximal renal tubules. One form is restricted to coated pit regions at the base of microvilli and has a cytoplasmic domain containing a sequence deduced from a partial complementary DNA encoding gp330. The other form is present over microvilli (and possibly at the base of microvilli as well) and lacks the cytoplasmic domain deduced from the complementary DNA. The complexes that are shed in Heymann nephritis contain either a portion of gp330 cleaved from the full-length molecule or a form of gp330 that lacks the cytoplasmic domain.