Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy

Research on liposome formulations has progressed from that on conventional vesicles to new generation liposomes, such as cationic liposomes, temperature sensitive liposomes, and virosomes, by modulating the formulation techniques and lipid composition. Many research papers focus on the correlation of blood circulation time and drug accumulation in target tissues with physicochemical properties of liposomal formulations, including particle size, membrane lamellarity, surface charge, permeability, encapsulation volume, shelf time, and release rate. This review is mainly to compare the therapeutic effect of current clinically approved liposome-based drugs with free drugs, and to also determine the clinical effect via liposomal variations in lipid composition. Furthermore, the major preclinical and clinical data related to the principal liposomal formulations are also summarized

Finding the ℓ-core of a tree

AbstractAn ℓ-core of a tree T=(V,E) with |V|=n, is a path P with length at most ℓ that is central with respect to the property of minimizing the sum of the distances from the vertices in P to all the vertices of T not in P. The distance between two vertices is the length of the shortest path joining them. In this paper we present efficient algorithms for finding the ℓ-core of a tree. For unweighted trees we present an O(nℓ) time algorithm, while for weighted trees we give a procedure with time complexity of O(nlog2n). The algorithms use two different types of recursive principle in their operation

Effectiveness of influenza vaccination in patients with end-stage renal disease receiving hemodialysis: a population-based study.

BackgroundLittle is known on the effectiveness of influenza vaccine in ESRD patients. This study compared the incidence of hospitalization, morbidity, and mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) between cohorts with and without influenza vaccination.MethodsWe used the insurance claims data from 1998 to 2009 in Taiwan to determine the incidence of these events within one year after influenza vaccination in the vaccine (N = 831) and the non-vaccine (N = 3187) cohorts. The vaccine cohort to the non-vaccine cohort incidence rate ratio and hazard ratio (HR) of morbidities and mortality were measured.ResultsThe age-specific analysis showed that the elderly in the vaccine cohort had lower hospitalization rate (100.8 vs. 133.9 per 100 person-years), contributing to an overall HR of 0.81 (95% confidence interval (CI) 0.72-0.90). The vaccine cohort also had an adjusted HR of 0.85 [95% CI 0.75-0.96] for heart disease. The corresponding incidence of pneumonia and influenza was 22.4 versus 17.2 per 100 person-years, but with an adjusted HR of 0.80 (95% CI 0.64-1.02). The vaccine cohort had lowered risks than the non-vaccine cohort for intensive care unit (ICU) admission (adjusted HR 0.20, 95% CI 0.12-0.33) and mortality (adjusted HR 0.50, 95% CI 0.41-0.60). The time-dependent Cox model revealed an overall adjusted HR for mortality of 0.30 (95% CI 0.26-0.35) after counting vaccination for multi-years.ConclusionsESRD patients with HD receiving the influenza vaccination could have reduced risks of pneumonia/influenza and other morbidities, ICU stay, hospitalization and death, particularly for the elderly

An ERP System Life Cycle-Wide Management and Support Framework for Small- and Medium-Sized Companies

Currently, the companies that have introduced the ERP system in Taiwan are mostly large enterprises. Due to the high cost of introduction and uncertain performance, however, ordinary small- and medium-sized enterprises can hardly afford the system. Thus, not only would a reference model for ERP life offer cycle-wide management support and assist large enterprises in evaluating and renewing the system, but it would also offer small- and medium-sized enterprises a set of procedures to successfully introduce the ERP system. The objective of this research is to explore the life cycle-wide management and support activities of an ERP system in order to establish a managerial model which can be used as a guideline for managers in dealing with their critical managerial activities. This study applied both the results from the literature review and Delphi study on the basis of Gowin\u27s Vee Approach. Through literature review, this research initially determined the life cycle-wide activities of the ERP system and then used the Grounded Theory to develop a prototype of the reference model for ERP life cycle-wide management and support. Subsequently, this study used the Delphi Method to collect the opinions of field experts. After analyzing and organizing the results, comparison and amendments were made to propose a final set of reference models for ERP life cycle-wide management and support. From the perspective of academic research, the authors believe that this study contributes to the development of a managerial model and provides prospective researchers with future directions in this subject area. As for the business sector, this managerial model can assist large enterprises through a better approach in management and support of the current ERP system, while small- and medium-sized enterprises are provided with a set of concrete steps to facilitate the successful introduction of the ERP system

Critical Factors of Adopting Enterprise Application Integration Technology: An Empirical Study on Larger Hospitals

As hospitals extend their service scope, they adopt more information systems. These systems are implemented in different timelines and the interfaces of databases become varied. Frequently, the exchange of information between various systems requires additional coordination or even manual input for unifying data. To embrace automation, the solution is to adopt enterprise application integration (EAI) technology, the middleware, to convert data from among various information systems to enable an efficient flow of data in the hospital. In this paper, we discuss and verify the impact factors on the integration levels of EAI by surveying larger hospitals above the regional level in Taiwan and testing a proposed research model. The findings of this study show that information technology infrastructure, hospital size, external pressure, internal pressure, and external support significantly affect the EAI level

Interferon-b Modulates Inflammatory Response in Cerebral Ischemia

BACKGROUND: Stroke is a leading cause of death in the world. In >80% of strokes, the initial acute phase of ischemic injury is due to the occlusion of a blood vessel resulting in severe focal hypoperfusion, excitotoxicity, and oxidative damage. Interferon-β (IFNβ), a cytokine with immunomodulatory properties, was approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis for more than a decade. Its anti-inflammatory properties and well-characterized safety profile suggest that IFNβ has therapeutic potential for the treatment of ischemic stroke. METHODS AND RESULTS: We investigated the therapeutic effect of IFNβ in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFNβ not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFNβ modulates ischemic brain inflammation were identified. IFNβ reduced central nervous system infiltration of monocytes/macrophages, neutrophils, CD4(+) T cells, and γδ T cells; inhibited the production of inflammatory mediators; suppressed the expression of adhesion molecules on brain endothelial cells; and repressed microglia activation in the ischemic brain. CONCLUSIONS: Our results demonstrate that IFNβ exerts a protective effect against ischemic stroke through its anti-inflammatory properties and suggest that IFNβ is a potential therapeutic agent, targeting the reperfusion damage subsequent to the treatment with tissue plasminogen activator

Apoptosis induction in BEFV-infected Vero and MDBK cells through Src-dependent JNK activation regulates caspase-3 and mitochondria pathways

Our previous report demonstrated that bovine ephemeral fever virus (BEFV)-infected cultured cells could induce caspase-dependent apoptosis. This study aims to further elucidate how BEFV activates the caspase cascade in bovine cells. BEFV replicated and induced apoptosis in Vero and Madin-Darby bovine kidney (MDBK) cells, and a kinetic study showed a higher efficiency of replication and a greater apoptosis induction ability of BEFV in Vero cells. Src and c-Jun N-terminal kinase (JNK) inhibitor, but not extracellular signal-regulated kinase (ERK) or p38 inhibitor, alleviated BEFV-mediated cytopathic effect and apoptosis. In BEFV-infected Vero and MDBK cells, BEFV directly induced Src tyrosine-418 phosphorylation and JNK phosphorylation and kinase activity, which was inhibited specifically by SU6656 and SP600125, respectively. The caspase cascade and its downstream effectors, Poly (ADP-ribose) polymerase (PARP) and DFF45, were also activated simultaneously upon BEFV infection. In addition, cytochrome c, but not Smac/DIABLO, was released gradually from mitochondria after BEFV infection. SU6656 suppressed Src, JNK, and caspase-3 and -9 activation, as well as PARP and DFF45 cleavage; SP600125 reduced JNK and caspase-3 and -9 activation, as well as PARP and DFF45 cleavage. Taken together, these results strongly support the hypothesis that a Src-dependent JNK signaling pathway plays a key role in BEFV-induced apoptosis. The molecular mechanism identified in our study may provide useful information for the treatment of BEFV