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Abstract Background Lymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM. Methods Sirolimus (trough level 5 - 10 ng/ml) was administered to ten female patients (42.4 ± 11.9 years) with documented progression. Serial pulmonary function tests and six-minute-walk-distance (6-MWD) assessments were performed. Results The mean loss of FEV1 was -2.30 ± 0.52 ml/day before therapy and a significant mean gain of FEV1 of 1.19 ± 0.26 ml/day was detected during treatment (p = 0.001). Mean FEV1 and FVC at baseline were 1.12 ± 0.15 l (36.1 ± 4.5%pred.) and 2.47 ± 0.25 l (69.2 ± 6.5%pred.), respectively. At three and six months during follow-up a significant increase of FEV1 and FVC was demonstrated (3 months ΔFEV1: 220 ± 82 ml, p = 0.024; 6 months ΔFEV1: 345 ± 58 ml, p = 0.001); (3 months ΔFVC: 360 ± 141 ml, p = 0.031; 6 months ΔFVC: 488 ± 138 ml, p = 0.006). Sirolimus was discontinued in 3 patients because of serious recurrent lower respiratory tract infection or sirolimus-induced pneumonitis. No deaths and no pneumothoraces occurred during therapy. Conclusions Our data suggest that sirolimus might be considered as a therapeutic option in rapidly declining LAM patients. However, sirolimus administration may be associated with severe respiratory adverse events requiring treatment cessation in some patients. Moreover, discontinuation of sirolimus is mandatory prior to lung transplantation.

Abstract Background Human Bronchial epithelial cells (hu-BEC) have been claimed to play a significant role in the pathogenesis of chronic inflammatory airway diseases like COPD. In this context IL-8 and GM-CSF have been shown to be key cytokines. Some antibiotics which are routinely used to treat lower respiratory tract infections have been shown to exert additional immunomodulatory or anti-inflammatory effects. We investigated whether these effects can also be detected in hu-BEC. Methods Hu-BEC obtained from patients undergoing lung resections were transferred to air-liquid-interface (ALI) culture. These cultures were incubated with cefuroxime (CXM, 10-62.5 mg/l), azithromycin (AZM, 0.1-1.5 mg/l), levofloxacin (LVX, 1-8 mg/l) and moxifloxacin (MXF, 1-16 mg/l). The spontaneous and TNF-α (10 ng/ml) induced expression and release of IL-8 and GM-CSF were measured using PCR and ELISA in the absence or presence of these antibiotics. Results The spontaneous IL-8 and GM-CSF release was significantly reduced with MXF (8 mg/l) by 37 ± 20% and 45 ± 31%, respectively (both p < 0.01). IL-8 release in TNF-α stimulated hu-BEC decreased by 16 ± 8% (p < 0.05) with AZM (1.5 mg/l). With MXF a concentration dependent decrease of IL-8 release was noted up to 39 ± 7% (p < 0.05). GM-CSF release from TNF-α stimulated hu-BEC was maximally decreased by 35 ± 24% (p < 0.01) with MXF (4 mg/l). Conclusion Using ALI cultures of hu-BEC we observed differential effects of antibiotics on spontaneous and TNF-α induced cytokine release. Our data suggest that MXF and AZM, beyond bactericidal effects, may attenuate the inflammatory process mediated by hu-BEC.

BackgroundThe genetic analysis of behavior in Drosophila melanogaster has linked genes controlling neuronal connectivity and physiology to specific neuronal circuits underlying a variety of innate behaviors. We investigated the circuitry underlying the adult startle response, using photoexcitation of neurons that produce the abnormal chemosensory jump 6 (acj6) transcription factor. This transcription factor has previously been shown to play a role in neuronal pathfinding and neurotransmitter modality, but the role of acj6 neurons in the adult startle response was largely unknown.Principal findingsWe show that the activity of these neurons is necessary for a wild-type startle response and that excitation is sufficient to generate a synthetic escape response. Further, we show that this synthetic response is still sensitive to the dose of acj6 suggesting that that acj6 mutation alters neuronal activity as well as connectivity and neurotransmitter production.Results/significanceThese results extend the understanding of the role of acj6 and of the adult startle response in general. They also demonstrate the usefulness of activity-dependent characterization of neuronal circuits underlying innate behaviors in Drosophila, and the utility of integrating genetic analysis into modern circuit analysis techniques.

A study was conducted to characterize the synthesis of (+-)-lacinilene C methyl ether by beta-naphthol to alpha-ketol oxidation. The oxidation of 2-naphthols to the ketols was anticipated in the experiment. A series of substituted 1-methyl-2-naphthols were determined to analyze the generality of the oxidation. Results indicated that a second oxygenation step of the naphthols were needed in the last step in the synthesis of the racemic natural product lacinilene C methyl ether.

The room-temperature optical pseudo-dielectric-functions of single-phase, single-crystalline rocksalt-structure MgxZn1-xO with Mg-content x between 0.68 and 1 were determined in the photon energy range from 0.75 to 9.10 eV using spectroscopic ellipsometry. The refractive index determined in the spectral region below the fundamental absorption edge decreases with increasing Mg content. The pseudo-dielectric-functions reveal structures caused in critical points due to electronic band-to-band transitions and free exciton formation at the fundamental band-gap transition. Standard model dielectric function approaches were applied for line shape analysis. Upon increase of the bond ionicity with increasing Mg content the energies of the band-to-band transitions as well as the fundamental-band-gap exciton binding energy parameters increase, while the Γ-point spin-orbit-splitting energy parameter decreases. We compare our results with the band-gap properties of wurtzite-structure MgxZn1-xO with Mg-content x between 0 and 0.5 obtained previously, and we discuss discontinuities across the phase transition. We provide estimates for the band gap bowing parameter of rocksalt-structure MgxZn1-xO and the band-gap value of rocksalt-structure ZnO. [ABSTRACT FROM AUTHOR]

The room-temperature optical pseudo-dielectric-functions of single-phase, single-crystalline rocksalt-structure [Mg.sub.x][Zn.sub.1-x]O with Mg-content x between 0.68 and 1 are found in the photon energy range by using spectroscopic ellipsometry. The estimates are provided for the band gap bowing parameter of rocksalt-structure [Mg.sub.x][Zn.sub.1-x]O and the band-gap value of rocksalt-structure ZnO.