Role of tacrolimus prolonged release in the prevention of allograft rejection

Successful management of the solid-organ transplant recipient begins with prevention of rejection and achieving a balance between insufficient and excessive immunosuppression. Standard tacrolimus therapy for prevention of solid-organ transplant rejection consists of 2 divided doses per day. In an effort to simplify tacrolimus dosing to once daily, a new formulation (tacrolimus prolonged release [PR]) was chosen for its combination of a similar extent of bioavailability and a substantially reduced rate of clearance. Several clinical conversion studies have now been completed using PR to clarify its pharmacokinetics, efficacy at prevention of allograft rejection, and safety profiles in solid-organ transplant patients. A cohort of 67 stable kidney transplant recipients was converted from standard tacrolimus to PR in an open-label, multicenter study in the United States and Canada. A second open-label, multicenter study was performed in liver transplant recipients with stable graft function on standard tacrolimus therapy converted to PR. A third conversion study was performed as an open-label study at 5 centers in the United States in stable pediatric liver transplant recipients. As medication noncompliance can significantly contribute to the incidence of graft rejection and graft loss in transplant recipients, a potentially significant advance in the transplant community’s ongoing mission to optimize prevention of rejection occurred with the development of a once-daily tacrolimus PR. The results of these preliminary studies suggest that select solid-organ transplant recipients converted to PR can be safely maintained using the same monitoring and patient care techniques historically used for standard tacrolimus therapy

PERANCANGAN APLIKASI E-PROCUREMENT DI PT. INDESSO AROMA

Penelitian ini mempelajari kinerja dan kepentingan dari sistem procurement di PT.Indesso Aroma dan mengembangkan aplikasi pendukung bagi sistem SAP saat ini. Metode analisis yang digunakan adalah perancangan e-procurement menggunakan metode OOAD dengan menggunakan notasi UML diagram. Dari analisis dan perancangan yang dilakukan, dihasilkan suatu aplikasi e-procurement yang memiliki beberapa fitur utama seperti Purchase Requisition, Purchase Order, Purchase Return, Supplier Katalog dan SupplierQuotation

PERANCANGAN APLIKASI E-PROCUREMENT DI PT. INDESSO AROMA

Penelitian ini mempelajari kinerja dan kepentingan dari sistem procurement di PT.Indesso Aroma dan mengembangkan aplikasi pendukung bagi sistem SAP saat ini. Metode analisis yang digunakan adalah perancangan e-procurement menggunakan metode OOAD dengan menggunakan notasi UML diagram. Dari analisis dan perancangan yang dilakukan, dihasilkan suatu aplikasi e-procurement yang memiliki beberapa fitur utama seperti Purchase Requisition, Purchase Order, Purchase Return, Supplier Katalog dan Supplier Quotation

Bicatalytic Allylation–Cross-Metathesis Reactions as γ-Carbonyl Cation Equivalents

The products corresponding to the reactions of arenes and γ-carbonyl cations may be obtained by a one-pot, bicatalytic process involving InCl3-catalyzed arene allylation and cross metathesis with electron-deficient alkenes. The process is successful with electronically neutral and electron-rich arenes, and modestly Lewis basic donor groups are tolerated with an increase in InCl3 loading from 10 mol% to 15 mol%, and in one case, 20 mol%

PERANCANGAN APLIKASI E-PROCUREMENT DI PT. INDESSO AROMA

Penelitian ini mempelajari kinerja dan kepentingan dari sistem procurement di PT.Indesso Aroma dan mengembangkan aplikasi pendukung bagi sistem SAP saat ini. Metode analisis yang digunakan adalah perancangan e-procurement menggunakan metode OOAD dengan menggunakan notasi UML diagram. Dari analisis dan perancangan yang dilakukan, dihasilkan suatu aplikasi e-procurement yang memiliki beberapa fitur utama seperti Purchase Requisition, Purchase Order, Purchase Return, Supplier Katalog dan SupplierQuotation

Characterization of Murine Interleukin-4 (IL-4) : Biological Activities and Initial Identification of Signal Transduction Mechanisms in IL-4-Mediated Macrophage Activation

IL-4, in the presence of macrophages (MΦs), has previously been demonstrated to be tumoricidal in vitro and in vivo, possibly through MΦ activation. In the current study, the biological activities of murine IL-4 on MΦs, and the initial identification of signal transduction mechanisms in IL-4-mediated MΦ activation were determined. Hamster MΦ were activated with IL-4 to study MΦ tumoricidal activity against hamster pancreatic adenocarcinoma in vivo.Through this initial study, it was observed that murine IL-4 is species specific and incapable of crossing the narrow phylogenetic barrier to hamster and perhaps rat (partially). The effects of murine IL-4 on allogeneic peritoneal and bone marrow-derived (14M1 .4 cell line) MΦ were then evaluated. Results showed a marked, dose-dependent stimulation of chemiluminescent oxidative burst by IL-4- activated MΦs, an activity which was IL-4 monoclonal antibody reversible. In addition, it appeared that 14M1.4 MΦ were more responsive than peritoneal MΦs to IL-4 in that they responded quicker and released greater quantities of reactive oxygen intermediates. Based on this preliminary work, the 14M14.4 MΦs were used to study the yet unknown signal transduction mechanisms in IL-4-mediated MΦ activation. By means of flow cytometric techniques and the membrane potential sensitive dye, DIOC6(3), it was shown that IL-4 caused no apparent biological but a statistically significant change in the membrane potential of MΦs. Using flow cytometry and indo-1AM, it was determined that intracellular calcium levels changed. An optimal concentration of 1L-4 caused a rapid increase in the initial (inhibited by BAPTA-AM, a specific intracellular chelator of calcium) and then sustained (inhibited by EGTA) level of intracellular calcium. Through assessments of chemiluminescence oxidative burst activity, it was demonstrated that the initial and sustained increase in intracellular calcium was required and important for IL-4 enhancement of the oxidative burst by 14M1.4 MΦs. Increase in production of IP3 but no change in levels of cAMP, immediate or delayed, were demonstrated using competitive binding assays. These findings were further supported by the fact that cholera toxin and prostaglandin E2 (agents which increase cAMP), did not enhance chemiluminescence, nor did PMA, a potent activator of PKC. Surprisingly, IL-4-stimulated MΦ were not cytolytic to tumor cell targets; yet, IL-4 was directly cytostatic to some of the same cell lines

Non-Fermi liquid behavior in a fluctuating valence system, the filled skutterudite compound CeRu_{4}As_{12}

Electrical resistivity $\rho$, specific heat C, and magnetic susceptibility $\chi$ measurements made on the filled skutterudite CeRu_4As_{12} reveal non-Fermi liquid (NFL) T - dependences at low T, i.e., $\rho$(T) $\sim$ T^{1.4} and weak power law or logarithmic divergences in C(T)/T and $\chi$(T). Measurements also show that the T - dependence of the thermoelectric power S(T) deviates from that seen in other Ce systems. The NFL behavior appears to be associated with fluctuations of the Ce valence between 3^+ and 4^+ rather than a typical Kondo lattice scenario that would be appropriate for an integral Ce valence of 3^+.Comment: 18 pages, 5 figure