Synergistic effect of combining theophylline and drugs that potentially elevate serum creatine kinase

An increase in the serum creatine kinase (CK) level is one of the side effects of theophylline;on rare occasions, the increase may be followed by rhabdomyolysis. Theophylline is often administered with drugs that potentially elevate the serum CK level (CK-elevating drugs) such as β-agonists and steroids. However, the effects of the combined treatment of theophylline and CK-elevating drugs have not been reported. We, therefore, retrospectively investigated the effects of combined treatment on the serum CK level, in391asthmatic outpatients. In this study, the number and type of the CK-elevating drugs administered, and the serum levels of CK and theophylline, were investigated. The patients were divided into four groups:the theophylline-treated and CK-elevating drug-treated group, the theophylline-treated and non-CK-elevating drug-treated group, the non-theophylline-treated and CK-elevating drug-treated group, and the non-theophylline-treated and non-CK-elevating drug-treated group. The theophylline-treated and CK-elevating drug-treated group showed about 100%higher serum CK levels (225IU/L) than any other group (102-124IU/L), and no increase in the serum theophylline level. This result indicates that there is a synergistic effect of theophylline and CK-elevating drugs on the serum CK level. The combined treatment of theophylline and CK-elevating drugs induces a synergistic increase in the serum CK level, indicating not pharmacokinetic but pharmacodynamic interactions with these drugs

A new unifying heuristic algorithm for the undirected minimum cut problems using minimum range cut algorithms

AbstractGiven a connected undirected multigraph with n vertices and m edges, we first propose a new unifying heuristic approach to approximately solving the minimum cut and the s-t minimum cut problems by using efficient algorithms for the corresponding minimum range cut problems. Our method is based on the association of the range value of a cut and its cut value when each edge weight is chosen uniformly randomly from the fixed interval. Our computational experiments demonstrate that this approach produces very good approximate solutions. We shall also propose an O(log2 n) time parallel algorithm using O(n2) processors on an arbitrary CRCW PRAM model for the minimum range cut problems, by which we can efficiently obtain approximate minimum cuts in poly-log time using a polynomial number of processors

Finding Subsets Maximizing Minimum Structures

We consider the problem of finding a set of k vertices in a graph that are in some sense remote. Stated more formally, given a graph G and an integer k, find a set P of k vertices for which the total weight of a minimum structure on P is maximized. In particular, we are interested in three problems of this type, where the structure to be minimized is a spanning tree ({sc Remote-MST}), Steiner tree, or traveling salesperson tour. We study a natural greedy algorithm that simultaneously approximates all three problems on metric graphs. For instance, its performance ratio for {sc Remote-MST} is exactly 4, while this problem is NP-hard to approximate within a factor of less than 2. We also give a better approximation for graphs induced by Euclidean points in the plane, present an exact algorithm for graphs whose distances correspond to shortest-path distances in a tree, and prove hardness and approximability results for general graphs

Finding Subsets Maximizing Minimum Structures

We consider the problem of finding a set of k vertices in a graph that are in some sense remote, stated more formally: "Given a graph G and an integer k, and a set P of k vertices for which the total weight of a minimum structure on P is maximized." In particular, we are interested in three problems of this type, where the structure to be minimized is a Spanning Tree (Remote-MST), Steiner Tree (Remote-ST), or Traveling Salesperson tour (Remote-TSP). We give a natural greedy approximation algorithm that simultaneously approximates all three problems on metric graphs. For instance, its performance ratio for Remote-MST is exactly 4, while it is NP -hard to approximate within a factor of less than 2. We also show a better approximation for graphs induced by Euclidean points in the plane, give an exact algorithm for graphs whose distances correspond to shortest-path distances in a tree, and give hardness and approximability results for general non-metric graphs

A new unifying heuristic algorithm for the undirected minimum cut problems using minimum range cut algorithms

AbstractGiven a connected undirected multigraph with n vertices and m edges, we first propose a new unifying heuristic approach to approximately solving the minimum cut and the s-t minimum cut problems by using efficient algorithms for the corresponding minimum range cut problems. Our method is based on the association of the range value of a cut and its cut value when each edge weight is chosen uniformly randomly from the fixed interval. Our computational experiments demonstrate that this approach produces very good approximate solutions. We shall also propose an O(log2 n) time parallel algorithm using O(n2) processors on an arbitrary CRCW PRAM model for the minimum range cut problems, by which we can efficiently obtain approximate minimum cuts in poly-log time using a polynomial number of processors

Epithelial Mesenchymal Transition in Human Ocular Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease (cGVHD) of the ocular surface and lacrimal gland is a vision-threatening condition that occurs after allogeneic bone marrow transplantation. In this study, we used immunohistochemistry and electron microscopy to investigate whether epithelial mesenchymal transition (EMT) contributed to the pathogenesis of ocular cGVHD. We detected down-regulation of E-cadherin and translocation of β-catenin from the intercellular junction to the cytoplasm and nucleus of cGVHD conjunctival basal epithelia and lacrimal gland myoepithelia. Notable findings included expression of Snail, an inducer of EMT, in the nucleus of ocular cGVHD epithelia. The fibrosis markers heat shock protein 47, α-smooth muscle actin, and fibroblast specific protein-1 were overexpressed in ocular cGVHD epithelia. In addition, p63, a marker of conjunctival basal epithelia, was observed in the nuclei of subconjunctival cells beneath disrupted basal lamina. Disrupted basal lamina and the presence of altered collagen bundles were observed in the cytoplasm and beneath cGVHD epithelia. In contrast, these observations were rarely observed in the normal conjunctiva and in Sjögren’s syndrome lacrimal gland epithelia. These findings together indicate that ocular cGVHD epithelia gain the mesenchymal phenotype and the capacity to migrate into the subepithelial stroma. Our findings suggest that EMT may be partially responsible for the conjunctival and lacrimal gland fibrosis found in patients with cGVHD