Plos One
-
In brain perfusion imaging, arterial spin labeling (ASL) is a noninvasive alternative to dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI). For clinical imaging, only product sequences can be used. We therefore analyzed the performance of a product sequence (PICORE-PASL) included in an MRI software-package compared with DSC-MRI in patients with steno-occlusion of the MCA or ICA >70%. ⋯ The PICORE ASL product sequence is sensitive for estimation of delayed tracer arrival, but cannot be recommended to measure CBF in steno-occlusive disease. ASL-sequences that are less sensitive to patient motion and correcting for delayed blood flow should be available in the clinical setting.
-
We have previously demonstrated that Sinupret, an established treatment prescribed widely in Europe for respiratory ailments including rhinosinusitis, promotes transepithelial chloride (Cl-) secretion in vitro and in vivo. The present study was designed to evaluate other indicators of mucociliary clearance (MCC) including ciliary beat frequency (CBF) and airway surface liquid (ASL) depth, but also investigate the mechanisms that underlie activity of this bioflavonoid. ⋯ Sinupret stimulates CBF, promotes transepithelial Cl- secretion, and increases ASL depth in a manner likely to enhance MCC. Our findings suggest that direct stimulation of CFTR, together with activation of Ca(2+)-dependent TMEM16A secretion account for the majority of anion transport attributable to Sinupret. These studies provide further rationale for using robust Cl- secretagogue based therapies as an emerging treatment modality for common respiratory diseases of MCC including acute and chronic bronchitis and CRS.
-
Comparative Study
Development of a novel inhalational model of invasive pulmonary aspergillosis in rats and comparative evaluation of three biomarkers for its diagnosis.
Aspergillus fumigatus, a thermotolerant fungus, is the main causative agent of invasive pulmonary aspergillosis (IPA) in immunocompromised patients that is associated with high mortality rates. Early diagnosis of IPA is crucial for mortality reduction and improved prognosis. An experimental inhalational model of IPA was developed in rats and the efficacy of three biomarkers, namely β-D-glucan (BDG), a panfungal marker, galactomannan (GM), a genus-specific marker, and A. fumigatus DNA, a species-specific marker was evaluated in serum and bronchoalveolar lavage (BAL) specimens at different time points postinfection for early diagnosis of IPA. ⋯ Our data show that BAL is a superior specimen than serum and combined detection of BDG, GM and A. fumigatus DNA provide a sensitive diagnosis of IPA in an experimental animal model. Moreover, combined detection of GM and DNA in BAL and detection of either GM or DNA in serum was also positive in 27 of 30 (90%) animals. For economic reasons and considering that the positive predictive value of BDG is low, the detection of GM and/or DNA in serum and BAL samples has the potential to serve as an integral component of the diagnostic-driven strategy in high-risk patients suspected for IPA.
-
Glucocorticoids are normally regarded as anti-inflammatory therapy for a wide variety of conditions and have been used with some success in treating sepsis and sepsis-like syndromes. We previously demonstrated that mice lacking the glucocorticoid receptor in the endothelium (GR EC KO mice) are extremely sensitive to low-dose LPS and demonstrate prolonged activation and up regulation of NF-κB. ⋯ As expected, control animals pre-treated with dexamethasone showed improvement in all parameters assayed. Mechanistically we demonstrate that GR EC KO mice show increased iNOS production and NF-κB activation despite treatment with dexamethasone.
-
Metabotropic glutamate receptors (mGluRs) are normally expressed in the central nervous system, where they mediate neuronal excitability and neurotransmitter release. Certain cancers, including melanoma and gliomas, express various mGluR subtypes that have been implicated as playing a role in disease progression. Recently, we detected metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in breast cancer and found that it plays a role in the regulation of cell proliferation and tumor growth. ⋯ In addition, loss of mGluR1 activity leads to reduced angiogenesis in a murine Matrigel sponge implant model as well as a murine tumor model. These results suggest a role for mGluR1 in breast cancer as a pro-angiogenic factor as well as a mediator of tumor progression. They also suggest mGluR1 as a potential new molecular target for the anti-angiogenic therapy of breast cancer.