Added value of diffusion-weighted imaging for evaluation of extramural venous invasion in patients with primary rectal cancer.

OBJECTIVE:: To evaluate the added value of diffusion-weighted imaging (DWI) to T 2 weighted imaging (T 2WI) for detection of extramural venous invasion (EMVI) in patients with primary rectal cancer. METHODS:: 79 patients (50 men, 29 females, mean age 67.4 years, range 37-87 years) who had undergone rectal MRI and subsequently received surgical resection were included. The rectal MRI consisted of T 2WI in three planes and axial DWI (b-values, 0, 1000 s mm-2). Two radiologists blinded to the pathologic results independently reviewed the T 2WI first, and then the combined T 2WI and DWI 4 weeks later. They recorded their confidence scores for EMVI on a 5-point scale (0: definitely negative and 4: definitely positive). The diagnostic performance of each reading session for each reader was compared by pairwise comparison of receiver operating characteristic curves. The area under the ROC curve (AUC) was considered as the diagnostic performance. The result of a histopathological examination served as the reference standard for EMVI. RESULTS:: For both readers, the diagnostic performance was not significantly different between the two image sets (for reader 1, AUC, 0.828 and 0.825, p = 0.9426 and for reader 2, AUC, 0.723 and 0.726, p = 0.9244, respectively). CONCLUSION:: There was no added value of DWI to T2WI for detection of EMVI in patients with primary rectal cancer. ADVANCES IN KNOWLEDGE:: High-resolution T2WI alone is sufficient to assess EMVI and a supplementary DWI has no added value in patients with primary rectal cancer.

Diagnostic performance of advanced modeled iterative reconstruction applied images for detecting urinary stones on submillisievert low-dose computed tomography.

Background Repeated computed tomography (CT) scans may be an issue in young adults with urinary stones. Therefore, it is important to know how far the dose can be reduced while maintaining the diagnostic performance. Purpose To generate a hypothesis that it is feasible to decrease the radiation dose to a sub-millisievert (mSv) level with the addition of advanced modeled iterative reconstruction (ADMIRE) while maintaining the sensitivity to standard-dose CT (SDCT) for the detection of urinary stones. Material and Methods Ninety-two consecutive patients with urinary stones underwent non-enhanced CT that consisted of standard (120 kVp, 200 mAs) and lose-dose (LDCT) (80 kVp, 60 mAs). The LDCT images were reconstructed separately with five different strengths of ADMIRE (hereafter, S1-S5) and filtered back projection (FBP). Two blinded radiologists independently recorded a number of urinary stones in the six LDCT datasets and SDCT. The sensitivity of each set for detecting urinary stones was compared using the McNemar test. Results A total of 240 urinary stones were analyzed. The sensitivities of the six LDCT datasets showed no difference (FBP, S1-S5, for reader 1: 78%, 79%, 79%, 80%, 80%, and 80%; for reader 2: 64%, 63%, 64%, 64%, 65%, and 66%, P > 0.05, respectively), which were lower than those of SDCT for both readers (reader 1: 88%; reader 2: 81%, P < 0.0001, respectively). Conclusion Despite the addition of ADMIRE, it may not be feasible to decrease the radiation dose to a sub-mSv level while maintaining the sensitivity to SDCT for the detection of urinary stones.

Enhancement of the skin-protective activities of Centella asiatica L. Urban by a nano-encapsulation process.

Aqueous extracts of Centella asiatica L. Urban were encapsulated by an edible biopolymer, gelatin, which has no effect on their cosmetic activities. The nanoparticles were w/o-type spherical liposomes that had an average diameter of 115.0nm. The encapsulation efficiency was estimated to be approximately 67%, which was relatively high for these aqueous extracts. The nanoparticles showed lower cytotoxicity (10%) in human skin fibroblast cells than the unencapsulated crude extract (15%) at 1.0mg/ml, this was possibly because a smaller amount of the extract was present in the nanoparticles. The nanoparticles efficiently reduced the expression of matrix metalloproteinase (MMP)-1 in UV-irradiated cells from 136.1% to 77.6% (UV-irradiated control) and inhibited hyaluronidase expression (>60%) at a concentration of 0.5mg/ml, which was higher than the levels produced by the unencapsulated crude extracts. The nanoparticles had a very high flux through mouse skin and also remained at relatively large concentrations in the derma when compared to the unencapsulated crude extracts. These results clearly indicate that the skin-protective activities of C. asiatica were significantly improved through the nano-encapsulation process. These findings also imply that a crude extract can be used and have the same efficacy as purified compounds, which should reduce the purification process and production costs.

Neuroprotective activity of the methanolic extract of Lonicera japonica in glutamate-injured primary rat cortical cells.

BACKGROUND: We previously reported that the extracts of several Korean medicinal plants showed neuroprotective activity in glutamate-injured primary culutres of rat cortical cells. OBJECTIVE: Among them, the effect of the methanolic extract of Lonicera japonica flower on the glutamate-induced neuronal cell death and its potential mechanism of action was investigated. RESULTS: Treatment by the methanolic extract of L. japonica flower significantly protected neuronal cells against glutamate-induced excitotoxicity. It decreased the calcium influx that accompanies the glutamate induced excitotoxicity of neuronal cells, and inhibited the subsequent overproduction of nitric oxide, reactive oxygen species and peroxide to the level of control cells. In addition, it preserved cellular activity of superoxide dismutase, an antioxidative enzyme reduced by glutamate insult. CONCLUSIONS: According to this data, the methanolic extract of L. japonica flower significantly protected neuronal cells against glutamate excitotoxicity via antioxidative activity.

Bioequivalence and tolerability of two clopidogrel salt preparations, besylate and bisulfate: a randomized, open-label, crossover study in healthy Korean male subjects.

BACKGROUND: Clopidogrel, a potent antiplatelet agent, reduces the risk for thrombotic events in patients with atherothrombotic diseases. Clopidogrel is marketed primarily as a bisulfate salt. A different salt preparation of clopidogrel, clopidogrel besylate, has been developed and might provide an additional treatment option for patients. OBJECTIVE: The aim of this study was to compare the pharmacokinetic, pharmacodynamic, and tolerability profiles of clopidogrel besylate with those of clopidogrel bisulfate to determine bioequivalence for the purposes of marketing approval. METHODS: A randomized, open-label, 2-period, single- and multiple-dose, comparative crossover study was conducted in healthy Korean male subjects. The subjects received either clopidogrel bisulfate or clopidogrel besylate as a single 300-mg oral loading dose (day 1) followed by a 75-mg/d (once daily) maintenance dose on days 2 to 6. After a 15-day washout period, subjects were administered the alternative salt preparation according to the same protocol. The plasma concentrations of clopidogrel and its primary metabolite (SR26334) were assessed using high-performance liquid chromatography/tandem mass spectrometry after administration of the loading dose. The platelet aggregation response to 10-mumol/L adenosine diphosphate was measured using turbidometric aggregometry during the single- and multiple-dosing periods and at steady state (day 6). Tolerability was monitored using physical examination, including vital sign measurements, and laboratory analysis. RESULTS: Forty-four subjects were enrolled and completed the study (mean [SD] age, 24.3 [2.7] years; weight, 70.0 [8.2] kg). The mean values for C(max), T(max), and AUC(0-t) with clopidogrel (parent drug) of clopidogrel besylate (5.2 ng/mL, 0.9 hour, and 10.1 ng/mL/h, respectively) were similar to those with clopidogrel bisulfate (5.4 ng/mL, 0.9 hour, and 10.3 ng/mL/h). The mean values for Cmax, AUC(0-t), and AUC(0-infinity) with the SR26334 of clopidogrel besylate (10.9 microg/mL, 38.8 microg/mL/h, and 43.0 microg/mL/h, respectively) were not significantly different from those with the SR26334 of clopidogrel bisulfate (11.9 microg/mL, 40.6 microg/mL/h, and 43.8 microg/mL/h). The mean values for maximal antiplatelet effect (Emax) and area under the time-effect curve (AUEC) with the 2 clopidogrel salt preparations were as follows: clopidogrel besylate, 58.8 h . % and 4299.1 h . % inhibition, respectively; and clopidogrel bisulfate, 61.7 h . % and 4406.9 h . % inhibition; these differences were not statistically significant. The 90% CIs for the ratios of the log-transformed C(max), AUC, E(max), and AUEC values were within the predetermined bioequivalence range of 80% to 125%. Three adverse events (6.8%) were reported during the study and included abdominal discomfort (1 subject [2.3%] in the group that received clopidogrel bisulfate), easy fatigability (1 subject [2.3%] immediately before administration of loading dose of clopidogrel besylate), and thrombocytopenia (1 subject [2.3%] in the group receiving the clopidogrel bisulfate). All adverse events were transient and mild. CONCLUSIONS: In these healthy Korean male subjects, the differences in the pharmacokinetic and pharmacodynamic properties between the 2 clopidogrel salt preparations did not reach statistical significance and met the regulatory requirements for bioequivalence. Both preparations were well tolerated.

The effects of fexofenadine at steady-state on sleep architecture: a study using polysomnography in healthy Korean volunteers.

OBJECTIVES: To compare the effects of a first-generation antihistamine, chlorpheniramine, with those of the second-generation antihistamine, fexofenadine, at steady-state, on nocturnal sleep architecture in healthy Korean volunteers using polysomnography and the Multiple Sleep Latency Test. We evaluated whether a genetic polymorphism of multi-drug resistance 1 gene (MDR1) could produce variations in pharmacokinetic and pharmacodynamic parameters of fexofenadine. DESIGN/METHODS: Ten healthy male volunteers received one capsule of fexofenadine 180 mg once each morning or chlorpheniramine 6 mg (2 mg in the morning and 4 mg after 12 h) for 3 days, in a single-site, randomized, double-blind, two-treatment, multiple-dosing, two-way crossover study, with a washout period of 7 days. Overnight polysomnography was measured on the second night of the treatment period. The Multiple Sleep Latency Test was carried out the next morning. Blood samples were taken for the assessment of fexofenadine pharmacokinetics and MDR1 genotyping on the third day. RESULTS: Compared with baseline and fexofenadine, chlorpheniramine significantly increased the latency in rapid eye movement (REM) sleep, with no significant decrease in the percentage of REM sleep. No significant change in latency for REM sleep or percentage REM sleep after dosing with fexofenadine was observed. There was no significant change in the daytime sleepiness with fexofenadine and chlorpheniramine. The effects of MDR1 genotypes and haplotypes on the pharmacokinetics and pharmacodynamics of fexofenadine were not significant. CONCLUSIONS: Our findings suggest that fexofenadine and chlorpheniramine at steady-state have no significant effect on nocturnal sleep variables and daytime sleepiness, when compared to baseline.