ABSTRACT
Noncompartmental analysis (NCA) is a primary analytical approach for pharmacokinetic studies, and its parameters act as decision criteria in bioequivalent studies. Currently, NCA is usually carried out by commercial softwares such as WinNonlin®. In this article, we introduce our newly-developed two R packages, NonCompart (NonCompartmental analysis for pharmacokinetic data) and ncar (NonCompartmental Analysis for pharmacokinetic Report), which can perform NCA and produce complete NCA reports in both pdf and rtf formats. These packages are compatible with CDISC (Clinical Data Interchange Standards Consortium) standard as well. We demonstrate how the results of WinNonlin® are reproduced and how NCA reports can be obtained. With these R packages, we aimed to help researchers carry out NCA and utilize the output for early stages of drug development process. These R packages are freely available for download from the CRAN repository.
ABSTRACT
OBJECTIVE: To test the effect of 1-nitrosocyclohexyl acetate (NCA), a newly developed nitroxyl (HNO) donor, on myofilaments and its action mechanism for the thiol in tropomyosin. METHODS: Trabeculae were dissected from the right ventricule of rat heart and mounted between a force transducer and a motor arm. The muscles were superfused with K-H solution (pH 7.4) at room temperature. Fura-2 salt was loaded into the trabeculae via electrophoresis, and the sarcomere length was set at 2.2-2.3 μm. Western blotting tested the change of tropomyosin. RESULTS: Twitch force increased in a dose dependent manner in the presence of NCA in the range of 20-100 μmol·L-1. Force increased (P0.05) with different frequencies (0.5-3.0 Hz) with NCA of 20 μmol·L-1 and Ca2+ of 0.5 μmol·L-1. Skinned force increased as compared to the control (P<0.05). The effect of NCA had characteristics of structure uniqueness. A cross-linking band in tropomyosin was seen by Western blotting under non-reducing condition. The thiol reducing agent dithiothreitol (DTT) both prevented and reversed HNO action. CONCLUSION: The donor of HNO, NCA, represents a new class of agents capable of directly sensitizing cardiac myofilaments to Ca2+. Post-translational thiol modification of the key regulatory myofilament protein (i.e. tropomyosin) may underlie the effect of NCA.
ABSTRACT
PURPOSE: The purpose of this study was to evaluate the diagnostic accuracy of Tc-99m labeled antigranulocyte antibody immunoscintigrapy in the diagnosis of osteomyelitis and compare with the results of triphasic bone scan. MATERIALS AND METHODS: The study population was 39 patients (22 male, 17 female) who had uncertain diagnoses of osteomyelitis. Fifteen patients had history of orthopedic surgery, and 5 had previous fracture. One milligram of monoclonal antibody against NCA-95 was labeled with 370 MBq of Tc-99m, injected intravenously, and 4 hour images were obtained. Triphasic bone scan images were obtained in 30 p;tients. The final diagnosis was confirmed by bacteriologic culture, biopsy or long term clinical follow up. RESULTS: Twenty one patients were confirmed to have osteomyelitis (1 acute, 20 chronic). Eighteen patients were without osteomyelitis. Antigranulocyte antibody immunoscintigraphy had a sensitivity of 71% (15/21), and a specificity of 89% (16/18), while the sensitivity and specificity of triphasic bone scan was 93% (13/14) and 38% (6/16), respectively. Antigranulocyte antibody scan showed higher specificity of 100% (11/11) in comparison with 33% (3/9) of triphasic bone scan in patients with history of orthopedic surgery or fracture. CONCLUSION: Antigranulocyte antibody immunoscintigraphy is more specific than that of triphasic bone scan and may be helpful in patients with history of surgery or fracture. However, sensitivity is lower than triphasic bone scan in the detection of chronic osteomyelitis.