Development of monitoring tool by pharmacists

Purpose: Drug side effects often lead to serious outcomes. Administration of second-generation antipsychotics has resulted in diabetic ketoacidosis and diabetic coma leading to death. Therefore, pharmacists are required to collect information on clinical test values, determine the appropriate test timing, and coordinate with doctors for further clinical laboratory orders, all of which are labor- and time-intensive tasks. In this study, we developed a side effect-monitoring tool and aimed to clarify the influence and efficiency of monitoring side effects by using the tool in patients taking atypical antipsychotics in whom it is necessary to check clinical test values such as blood sugar levels. Methods: We extracted clinical test values for patients treated with second-generation antipsychotics from electronic medical records. The test values are automatically displayed in the side effect grade classification specified by CTCAE ver. 4.0. A database was constructed using scripts to provide alerts for the timing of clinical testing. The pharmacist used this tool to confirm clinical test values for patients taking medication and requested the physician to inspect orders based on the appropriate test timings. Results: The management tool reduced the pharmacists’ effort in collecting information on patients’ prescription status and test values. It enabled patients to undergo tests at the appropriate time according to the progression of glucose metabolism and allowed for easy monitoring of side effects. Conclusion: The results suggested that regardless of pharmacists’ experience or skill, the introduction of this tool enables centralization of side-effect monitoring and can contribute to proper drug use

DNA Lesions Induced by Replication Stress Trigger Mitotic Aberration and Tetraploidy Development

During tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration, which induce situations identical to the initial stages of cancer development, trigger tetraploidy/aneuploidy generation in association with mitotic aberration. Although oncogene acceleration primarily induces DNA replication stress and the resulting lesions in the S phase, these lesions are carried over into the M phase and cause cytokinesis failure and genomic instability. Unlike directly induced DNA double-strand breaks, DNA replication stress-associated lesions are cryptogenic and pass through cell-cycle checkpoints due to limited and ineffective activation of checkpoint factors. Furthermore, since damaged M-phase cells still progress in mitotic steps, these cells result in chromosomal mis-segregation, cytokinesis failure and the resulting tetraploidy generation. Thus, our results reveal a process of genomic instability generation triggered by precancerous DNA replication stress

Cyclohexanol biodegradation genes: a pathway of opportunities

We have now determined the complete gene sequence of the cyclohexanol (chn) degradation pathway in Acinetobacter sp. NCIMB 9871 as well as the putative genes for the \u3b2-oxidation of adipic acid to acetyl-CoA and succinyl-CoA. In addition, a new insertion sequence, potentially useful in strain characterization, was identified. Knowledge of the nucleotide sequence of the chn genes was used to construct clones of Escherichia coli that would overproduce the requisite biocatalysts: a flavin monooxygenase (ChnB; cyclohexanone 1,2-monooxygenase [CHMO]), a ring-opening hydrolase (ChnC; \u3b5-caprolactone hydrolase) and three oxido-reductases (ChnA, cyclohexanol dehydrogenase; ChnD, 6-hydroxyhexanoate dehydrogenase; and ChnE, 6-oxohexanoate dehydrogenase). Besides the well known application of CHMO as a Baeyer-Villiger biocatalyst that carries out stereoselective oxidations of a wide variety of ketones to the corresponding lactones, potential applications of the Chn biocatalysts in the development of "green" bioprocesses such as an "envirocompatible" synthesis of adipic acid are discussed.NRC publication: Ye

Identification of a transcriptional activator (ChnR) and a 6-oxohexanoate dehydrogenase (ChnE) in the cyclohexanol catabolic pathway in Acinetobacter sp. Strain NCIMB 9871 and Localization of the Genes That Encode Them

NRC publication: Ye