Objective: In the previous study, the CYP database was constructed in order to relate drug-drug interactions to the CYP metabolic information of the package inserts.  In this study, we evaluated the clinical usefulness of the CYP database by using the Pharmaceutical and Medical Devices Agency (PMDA) Drug Monitoring Information.
Methods: We examined the drugs in CYP isoform responsible for drug metabolism.  The age, sex, suspect drugs and co-administered drugs were extracted from 6,236 cases of the PMDA database of drug monitoring from January till November of 2008.
Results: Twenty-three percent of all cases had co-administered drugs.  Forty-five percent of these cases were metabolized both suspect and co-administered drugs by the same CYP isoform, and three fourths of these cases were able to be detected only by the CYP database.  In addition, the administration of substrate medicines in combination with substrate medicines was the largest (57%), followed by cases of substrate medicines in combination with inhibitor medicines (28%).  Seventy-seven percent of the suspect drugs that had a large number of reported cases of side effects were substrate medicines, and the frequency of co-administration with substrate medicines was very high.
Conclusion: These data suggest that the CYP database, being used together with package inserts, might be a clinically useful tool to avoid adverse events caused by drug-drug interactions.

PURPOSE: Intracranial administration of lipopolysaccharide (LPS) is known to elicit a rapid innate immune response, activate glial cells in the brain, and induce depression-like behavior. However, no study has focused on the changes in glial cells induced by intraperitoneal injection of LPS in vivo.METHODS: Ten adult male Fischer F344 rats underwent [¹¹C]PK11195 PET before and 2 days after intraperitoneal injection of LPS to evaluate the changes in glial cells. The difference in standardized uptake values (SUV) of [¹¹C]PK11195 between before and after injection was determined.RESULTS: There was a cluster of brain regions that showed significant reductions in SUV. This cluster included the bilateral striata and bilateral frontal regions, especially the somatosensory areas.CONCLUSIONS: Changes in activity of glial cells induced by the intraperitoneal injection of LPS were detected in vivo by [¹¹C]PK11195 PET. Intraperitoneal injection of LPS is known to induce depression, and further studies with [¹¹C]PK11195 PET would clarify the relationships between neuroinflammation and depression.
Adult ; Animals ; Brain ; Depression ; Electrons ; Humans ; Immunity, Innate ; Injections, Intraperitoneal ; Lipopolysaccharides ; Male ; Neuroglia ; Positron-Emission Tomography ; Rats ; Rats, Inbred F344

PURPOSE: Intracranial administration of lipopolysaccharide (LPS) is known to elicit a rapid innate immune response, activate glial cells in the brain, and induce depression-like behavior. However, no study has focused on the changes in glial cells induced by intraperitoneal injection of LPS in vivo. METHODS: Ten adult male Fischer F344 rats underwent [¹¹C]PK11195 PET before and 2 days after intraperitoneal injection of LPS to evaluate the changes in glial cells. The difference in standardized uptake values (SUV) of [¹¹C]PK11195 between before and after injection was determined. RESULTS: There was a cluster of brain regions that showed significant reductions in SUV. This cluster included the bilateral striata and bilateral frontal regions, especially the somatosensory areas. CONCLUSIONS Changes in activity of glial cells induced by the intraperitoneal injection of LPS were detected in vivo by [¹¹C]PK11195 PET. Intraperitoneal injection of LPS is known to induce depression, and further studies with [¹¹C]PK11195 PET would clarify the relationships between neuroinflammation and depression.

Purpose: Total or proximal gastrectomy of the upper-third early gastric cancer (u-EGC) often causes severe post-gastrectomy syndrome, suggesting that these procedures are extremely invasive for patients without pathologically positive lymph node (LN) metastasis. This study aimed to evaluate the clinical applicability of a stomach function-preserving surgery, local resection (LR), with prophylactic left gastric artery (LGA)-basin dissection (LGA-BD). Materials and Methods: The data of patients with u-EGC (pathologically diagnosed as T1) were retrospectively analyzed. Total gastrectomy was performed in 30 patients, proximal gastrectomy in 45, and subtotal gastrectomy in 6; the LN status was evaluated assuming that the patients had already underwent LR + LGA-BD. This procedure was considered feasible in patients without LN metastases or in patients with cancer in the LGA basin. The reproducibility of the results was also evaluated using an external validation dataset. Results: Of the 82 eligible patients, 79 (96.3%) were cured after undergoing LR + LGA-BD, 74 (90.2%) were pathologically negative for LN metastases, and 5 (6.1%) had LN metastases, but these findings were only observed in the LGA basin. Similarly, of the 406 eligible tumors in the validation dataset, 396 (97.5%) were potentially curative. Tumors in the lesser curvature, post-endoscopic resection status, and small tumors (<20 mm) were considered to be stronger indicators of LR + LGA-BD as all subpopulation cases met our feasibility criteria. Conclusions More than 95% of the patients with u-EGC might be eligible for LR + LGA-BD.This function-preserving procedure may contribute to the development of u-EGC without pathological LN metastases, especially for tumors located at the lesser curvature.