Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.     

Experimentelle und klinische Studie zur Stabilit?t einer Osteosyntheseplatte für den atrophen Unterkiefer

ZusammenfassungHintergrund Der Anteil an älteren Patienten steigt ständig und damit auch die Zahl traumatischer altersbedingter Verletzungen wie Frakturen des Unterkiefers. Die Frakturversorgung bei älteren Menschen stellt spezielle Anforderungen. Durch das Design einer neu entwickelten Osteosyntheseplatte sollte versucht werden, diese speziellen Gesichtspunkte zu erfüllen.Material und Methoden Im Gegensatz zu den 2.0-Miniplatten (Medartis AG, Basel) besitzt die Pencilbone-2.0-Platte, die aus diesen Miniplatten entwickelt wurde, einen oval geformten Mittelsteg zur Stabilisierung des frakturnahen Knochens und zwei sphärische Gleitlöcher jenseits der Fraktur. An den verstärkten Teil der Osteosyntheseplatte schließen sich jeweils 2 bzw. 3 normale unverstärkte Löcher an, die sich sehr leicht an den frakturfernen Knochen adaptieren lassen. Dies ermöglicht dem Operateur den intraoralen Zugangsweg und eine Handhabung, welche er von der Miniplattenosteosynthese gewohnt ist, bietet aber gleichzeitig eine höhere Stabilität im Vergleich mit den Standard-2.0.-Miniplatten.Ergebnisse und Diskussion Nach experimentellen und biomechanischen Untersuchungen, die alle positive Ergebnisse zeigten, wurde die neue Platte zwischen Oktober 2000 und November 2001 in zwei Kliniken an 16 Frakturen des atrophischen Unterkiefers bei 14 Patienten erfolgreich angewendet. 15 Frakturen heilten primär, lediglich bei einer Fraktur wurde eine neue operative Versorgung wegen Knochendislokation nach erneutem Sturz notwendig.     

Sulfasalazine treatment in juvenile chronic arthritis: an open study.

In an open study, the effect of sulfasalazine was evaluated in the treatment of juvenile chronic arthritis (JCA). Forty-one patients, i.e., 27 boys and 14 girls with JCA under 16 years of age, were included in the study. In all of them, treatment with nonsteroidal antiinflammatory drugs (NSAID) had been unable to control the disease. The patients were divided in 4 subgroups depending on the mode of onset and evolution (Type I = systemic onset, Type II = polyarticular form. Type IIIa and Type IIIb = pauciarticular form). Remission was achieved in 21 patients, significant improvement in 12. Status was unchanged in 4 patients and worsened in 3. In 5 patients side effects were observed, which forced interruption of treatment in 4. Sulfasalazine was stopped in 7 patients: for toxicity in 4 and for inefficacy in 3. In 7 other patients the treatment was terminated after a prolonged remission. These promising results must be confirmed in a double blind versus placebo study, preferably restricted to type III JCA.     

Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha

Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine.     

Effect of ozone exposure on allergic sensitization and airway inflammation induced by dendritic cells

BACKGROUND: Epidemiological studies suggest that ozone exposure is related to increased asthma symptoms. Dendritic cells (DCs) are the principal antigen-presenting cells in the airways. OBJECTIVE: We have examined whether ambient doses of ozone (100 ppb for 2 h) enhance allergic sensitization and/or airway inflammation in a mouse model. METHODS: C57BL/6 mice were sensitized to inhaled ovalbumin (OVA) by intratracheal instillation of OVA-pulsed DCs on day 0. Daily exposure to OVA aerosol on days 14-20 resulted in an eosinophilic airway inflammation, as reflected in bronchoalveolar lavage fluid and lung histology. In a first experiment, mice were exposed to ozone or room air immediately prior to and following sensitization. Subsequently, we tested the effect of ozone exposure during antigen challenge in DC-sensitized mice. RESULTS: Exposure to ozone during sensitization did not influence airway inflammation after subsequent allergen challenge. In contrast, in sensitized mice, challenge with OVA together with ozone (days 14-20) resulted in enhanced airway eosinophilia and lymphocytosis, as compared with mice exposed to OVA and room air (1.91 x 106 +/- 0.46 x 106 vs. 0.16 x 106 +/- 0.06 x 106 eosinophils/mL lavage fluid; P = 0.015; 0.49 x 106 +/- 0.11 x 106 vs. 0.08 x 106 +/- 0.03 x 106 lymphocytes/mL lavage fluid; P = 0.004). Ozone exposure without subsequent OVA exposure did not cause airway inflammation. CONCLUSION: Ozone exposure does not increase allergic sensitization but enhances antigen-induced airway inflammation in mice that are sensitized via the airways.     

Cytological detection of epithelial dysplasia in the oral mucosa using Feulgen-DNA-image cytometry

Cytological scrape material of the oral mucosa from 114 patients with epithelial dysplasia and with oral cancer was stained with the Feulgen-reaction and investigated with an image analyzer. The size and the integrated optical density of cell nuclei, and four chromatin texture features were measured. All tumor slides contained cell nuclei with DNA greater than 5c, 16% of the slides had cell nuclei with DNA greater than 8c. A total of 14.5% of the tumor patients showed significantly increased DNA values in nuclei distant from the tumor. Two smears with severe epithelial dysplasia showed nuclei with DNA greater than 5c both in the tumor material and far from the tumor. Texture analysis allowed discrimination between benign, dysplastic and malignant smears. No correlation was found between DNA content and tumor staging. Image cytometry was a reliable method for detecting tumor cells. Epithelial dysplasia in areas distant from the tumor is probably due to "field canceration" of the epithelium.