Quantitative assessment of the relevance of organic-anion-transporting-polypeptide 1B1 and 2B1 polymorphisms in fexofenadine pharmacokinetic variants via pharmacometrics / 药物分析学报

Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmaco-kinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma con-centration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokinetic-pharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic poly-morphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population phar-macometrics study will be a very useful starting point for fexofenadine precision medicine.

The Statistical Analysis on the Legal Autopsy Cases in Gwang-ju and Chonnam Area of Korea in 2009 and 2010 / 대한법의학회지

Analyzing the data associated with the causes and manners of death in each region is important to make policies for the national public health, because it can be basis for prevention of future crimes and treatment of diseases. To establish regional basic data of the 245 autopsy cases performed at the department of Forensic Medicine of Chonnam National University Medical School in 2009 and 2010, each case was statistically analyzed according to the causes of death and the manners of death. The results are as follows; 1) the total number of legal autopsy was 245 (178 males and 67 females). The number of the 5th decade (64 cases) and the 6th decade (51 cases) occupied near 50 percent (46.9%) of total cases. 2) unnatural deaths were 154 cases (62.9%), and natural deaths were 91 cases (37.1%). In 154 cases of unnatural deaths, suicides were 27 cases (11.0%), homicides were 52 cases (21.2%), accidental deaths were 43 cases (17.6%), and undetermined deaths were 32 cases (13.1%). 3) Among 91 natural deaths, deaths of cardiac origin were 57 cases (62.6%) and it was a leading cause of death in natural deaths. Deaths due to disease of cerebral vascular system were 11 cases (12.1%), deaths due to respiratory system were 9 cases (9.9%). 4) Child deaths under the age of 10 were 9 cases (3.6%). Four cases were homicide, 2 cases were accident, and 3 cases were natural deaths. Conclusively, in these area victims between thirties and forties are taking the most proportion, unnatural deaths are more than natural deaths. In unnatural deaths, the order of frequency is homicide, accidental death, suicide, in natural death, neurocardiovacular disease is predominant.

Delayed Rupture of Traumatic Intracranial Aneurysm Developed by Minor Head Trauma / 대한법의학회지

Traumatic subarachnoid hemorrhage (tSAH) can be almost immediately fatal. However, sudden death due to tSAH caused by delayed aneurysmal rupture is very rare sequela of mild head trauma. We experienced a death case of a 47-year-old woman who had subarachnoid hemorrhage and intraventricular hemorrhage 3 days after head trauma. Delayed death after any kinds of trauma is important to forensic and legal aspects. Herein we report a case of fatal subarachnoid hemorrhage caused by delayed rupture of traumatic aneurysm.

Clinical features of gastritis cystica profunda in patients without history of gastric surgery (Gastric Cancer Patients vs. Non-cancerous Patients) / 대한내과학회지

BACKGROUND: The relationship between gastric cancer and gastritis cystica profunda (GCP) has been frequently reported on, but there have been no systemic studies on whether or not GCP is a precancerous lesion. The aim of this study is to retrospectively analyze the groups in which some of the patients were accompanied by carcinoma and the other patients were non-cancerous (35 GCP cases were without previous surgery). METHODS: From February 2000 through July 2005, 35 cases of GCP without antecedent gastric surgery were diagnosed histologically. We reviewed the medical records, the endoscopic findings and the histologic findings of the patients. RESULTS: In these cases, the age ranged from 33 and 82 years (mean: 63+/-10.1 years). The endoscopic findings of GCP were various: there were 6 erosions and 9 ulcers in the cancer group and 12 polyps in the non-cancer group (p=0.000). The mean size of the lesions was 21.4+/-17.8 mm in the cancer group and 14.6+/-9.3 mm in the non-cancer group (p=0.337). Hypertension was associated with 15 cases (42.9%) in the cancer group and with 2 cases (5.7%) in the non-cancer group (p=0.000). There were 13 smokers (37.1%) in the cancer group and 6 smokers (17.1%) in the non-cancer group (p=0.028). For the histologic findings, 6 GCP patients were associated with dysplasia of adenomas, 4 GCP patients with intestinal metaplasias and 28 GCP patients (80%) with precancerous lesions and carcinomas. CONCLUSIONS: In this study, 18 GCP patients (51.4%) were associated with carcinoma and 10 GCP patients (29%) were associated with precancerous lesions. These results suggest that GCP is a precancerous or paracancerous lesion and it may be one step in the development of carcinoma. The underlying mechanisms of gastric carcinogenesis might be confirmed if we investigate the gene mutations and environmental differences of documented GCP cases that are without previous surgery.