The pharmacology and clinical application of traditional Chinese medicine has been extensively documented. We have used an in vitro model system, PC12 cells, to demonstrate the presence of neuroactive compounds in Ganoderma lucidum (lingzhi). Ganoderma extract induced the neuronal differentiation of PC12 cells and prevented nerve growth factor-dependent PC12 neurons from apoptosis. Moreover, these effects of ganoderma might be mediated via the ras/extracellular signalregulated kinase (Erk) and cAMP-response element binding protein (CREB) signaling pathways, as demonstrated by the phosphorylation of Erk1, Erk2 and CREB. Thus, our data not only present the first evidence of the presence of neuroactive compounds that mediate the neuronal differentiation and neuroprotection of the PC12 cells, but also reveal the potential signaling molecules involved in its action. ß
Airway epithelial cells are the first targets of environmental stimuli and local cytokines. Pyocyanin-induced synergism with interleukin (IL)-1 or tumour necrosis factor (TNF) in triggering IL-8 release has been documented previously. In this study, IL-8 mRNA and protein expression were examined in cultured human bronchial epithelial cells (BEAS-2B) stimulated with pyocyanin alone, and in combination with IL-1beta or phorbol 12,13-dibutyrate (PDBu) in the absence and presence of a group of glucocorticoids. IL-8 mRNA was measured by RT-PCR, and IL-8 protein by ELISA (cell supernatants). Pyocyanin alone produced no increase in IL-8 mRNA and release. However, pyocyanin upregulated the stimulatory effect of IL-1beta or PDBu on the release of IL-8 in a dose-dependent manner. The stimulatory effect of pyocyanin on the IL-1beta- or PDBu-stimulated IL-8 release was reduced in the presence of dexamethasone, budesonide, and fluticasone. Budesonide and fluticasone were 10-fold more potent than dexamethasone. The protein kinase C (PKC) inhibitor, Go6976, also significantly reduced the stimulatory effect of pyocyanin on IL-1beta, and PDBu increased IL-8 release. In conclusion, this study shows that PKC signal pathway seems to be involved in the pyocyanin-mediated upregulation of the IL-1beta and PDBu-induced IL-8 release in BEAS-2B cells. These findings suggest that a vicious cycle perpetuating inflammation may exist in the biologic milieu of bronchiectatic patients infected with Pseudomonas aeruginosa due to the production of pyocyanin. The priming action of pyocyanin appears to be blocked by glucocorticoids, thus providing in vitro data in support of the clinical efficacy of inhaled glucocorticoids as anti-inflammatory drugs.
Details of a new low power fast Fourier transform (FFT) processor for use in digital television applications are presented. This has been fabricated using a 0.6-m CMOS technology and can perform a 64 point complex forward or inverse FFT on real-time video at up to 18 Megasamples per second. It comprises 0.5 million transistors in a die area of 7.8 2 8 mm 2 and dissipates 1 W. The chip design is based on a novel VLSI architecture which has been derived from a first principles factorization of the discrete Fourier transform (DFT) matrix and tailored to a direct silicon implementation.
BackgroundEmpiric therapy is a mainstay of the inpatient management of urinary tract infections (UTIs), and the choice of empiric antibiotic is shaped by local epidemiology and patient risk factors and comorbidities. Pathogen identification (ID) and antibiotic susceptibility testing (AST) provide information that can guide adjustments in therapy, allowing de-escalation to more targeted, narrow-spectrum antibiotics.MethodsReal-world data (hospital billing claims) from 2017 was used to extract relevant information from general hospitals on inpatients with bacterial UTIs including patient demographics and antibiotics line of therapy progression. Patients were projected to the USA national event totals and validated with other projection-related data sources (HCUP) and secondary market research. Data obtained in the claims analysis was validated by primary market research (PMR).ResultsAnalysis of 33M claims identified 169K patients with a code for UTI; in at least one-third of patients, there were no codes associated with ID/AST assays. Among those with codes for ID/AST assays, the vast majority were performed in the first 3 days following hospital admission. Approximately two-thirds of patients with associated ID/AST codes were already receiving an antibiotic when the assays were performed, which was assumed to be the empiric treatment. Analysis of the line of antibiotic therapy progression in patients where ID/AST was performed identified subsequent changes in antibiotic prescribing in approximately one-third of patients within 3 days, compatible with changes due to delivery of conclusive results and were interpreted as a transition from empiric to targeted treatment.ConclusionTo the best of our knowledge, this is the first attempt at understanding the impact of ID/AST assays on prescribing practices with basis on analysis of claims data. Our results align with PMR conducted by DRG internally, supporting the validity of this methodology. Although this claims analysis delivers reliable data when claims are associated with ID/AST assays, it is limited by incompletely filled claims, which may underestimate the use of these assays.Disclosures
All authors: No reported disclosures.
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