Development of tiotropium inhalation formulations for the treatment of chronic obstructive pulmonary disease

Tiotropium, a longer acting anticholinergic bronchodilator, has been widely used for treatment of chronic obstructive pulmonary disease (COPD). To improve the therapeutic effect of tiotropium, we developed various inhalation microparticular formulations of tiotropium using starch, hyaluronate, bovine serum albumin (BSA), and poly(lactide-co-glycolide) (PLGA). All formulations showed ~90 % inhalation efficiency in the lung epithelium of BALB/c mice after initial administration. Interestingly, when compared to other formulations using starch, hyaluronate, and BSA, the inhalation formulation of tiotropium using PLGA showed longer drug residence (up to 7 days) in in vivo lung epithelium. We believe that this microparticle system is expected to improve the treatment efficacy for the patients with COPD by maintaining drug therapeutic effect during the extended period after initial inhalation.     

超声检查在肾结石诊断中的应用回顾

临床上肾结石是引起腰痛的病因之一,超声检查是首选影像技术。一些疾病的声像图表现可误诊为肾结石;而结石的大小、部位、积水等原因也直接影响诊断正确率。识别肾内类似结石的其它结构,并充分认识到影响诊断的因素,可提升诊断的准确率,避免因假阳性干扰临床医师的救治,并可适时的选择其他影像技术协助诊断。本文重点介绍可误诊为肾结石的疾病的声像图特征,并讨论影响肾结石诊断准确率的几个因素。     

Dependence Potential of Propofol: Behavioral Pharmacology in Rodents

Propofol is an anesthetic commonly used to provide sedation or to induce and maintain an anesthetic stated. However, there are reports which indicate propofol may cause psychological dependence or be abused. In the present study, we used various behavioral tests including climbing test, jumping test, conditioned place preference, and self-administration test to assess the dependence potential and abuse liability of propofol compared to a positive control (methamphetamine) or a negative control (saline or intralipid). Among the tests, the conditioned place preference test was conducted with a biased method, and the selfadministration test was performed under a fixed ratio (FR) 1 schedule, 1 h per session. No difference was found in the climbing test and jumping test, but propofol (30 mg/kg, i.p.) increased the rewarding effect in the conditioned place preference test, and it showed a positive reinforcing effect compared to the vehicle. These results indicate that propofol tends to show psychological dependence rather than physical dependence, and it seems not to be related with dopaminergic system.     

Environmental assessment of estrogenic pollutants in Nam River of Korea using indirect competitive ELISA and E-screen assay

Endocrine disrupting chemicals (EDCs) in ecosystem have raised a serious public health concern due to their potential adverse effects of interfering endogenous endocrine systems of organisms, including human being. Nam River is a main stream in southern part of Korea and has been used as a source of drinking water and for a variety of water-based activities of the people in this region. For the present study, water samples were collected from 11 different locations of Nam River, including two wastewater treatment plants (WWTPs). The collected water samples were analyzed with indirect competitive enzymelinked immunosorbent assay (IC-ELISA) and E-screen assay for the quantitative measurement of estrogens and the evaluation of their estrogenic activities, respectively. IC-ELISA showed that significant levels of estrogens (as estrogen equivalent concentration (EEC)) were present in WWTPs influents (5.537 ng-EEC/L for Jinju WWTP and 16.817 ng-EEC/L for Gyeongsang national university WWTP, respectively), but not detected in other river water samples. E-screen assay also showed similar results of the high estrogenic activities in WWTP influents. Unlike IC-ELISA, however, the results of E-screen revealed the presence of some weak estrogenic activities in all of the environmental water samples other than WWTP. One of the possible reasons of the difference is the presence of some estrogenic pollutants which are structurally unrelated to estrogens. From this, it is considered that the IC-ELISA method is a quick and reliable assay for the 1^st-trial screening of large number of environmental samples with a relatively low cost. The present study could be helpful for the assessment of estrogen pollutants in environmental samples.     

Effect of a mixed solution of sodium hyaluronate and carboxymethyl cellulose on upper limb dysfunction after total mastectomy: a double-blind, randomized clinical trial

Restricted shoulder mobility is a major upper limb dysfunction related to lower quality of life and disability after breast cancer surgery. We hypothesized that sodium hyaluronate?Ccarboxymethyl cellulose (HA?CCMC) applied to the surface of the pectoralis major muscle after mastectomy would significantly reduce pain and improve range of motion (ROM) of the shoulder in breast cancer patients. We conducted a double-blind, randomized controlled study to evaluate the clinical efficacy and safety of HA?CCMC in the prevention of upper limb dysfunction after total mastectomy (TM). A total of 99 women with breast cancer were randomly assigned to one of two groups. In the HA?CCMC group (n?=?50), a mixed HA?CCMC was applied to the surface of the pectoralis major and serratus anterior muscle after TM. In the control group (n?=?49), TM was performed without the use of HA?CCMC. The primary outcomes were ROM of the shoulder and motion-related pain assessed using a numeric rating scale measured before surgery (T0) and 3 (T1) and 6?months (T2) after surgery. Secondary outcomes included disabilities of the arm, shoulder, and hand (DASH) and the pectoralis minor length test. Compared with the control group, the HA?CCMC group showed greater reductions in postoperative restriction of total shoulder ROM (sum of flexion and horizontal abduction) at 3?months (10.20°, P?=?0.004). Mean pain levels related to flexion and horizontal abduction were significantly lower in the HA?CCMC group (?1.32 and ?0.93, respectively, P?<?0.05). The DASH score was lower (?4.94; P?=?0.057) in the HA?CCMC group at T2. No adverse effect was observed in either group. These results provide evidence that HA?CCMC may provide pain relief and improve ROM of the shoulder without causing adverse effects. The effect on pectoralis tightness should be investigated in further studies.     

Measurement of quality of life and participant experience with the mindfulness-based stress reduction program

Clinical studies of MBSR have reported efficacy in treating pain, mood disorders, arthritis, sleep disturbances, and stress. Several academic medical institutions in the United States offer MBSR to their patients, but it has never been offered at Mayo Clinic. The objective of this study was to collect quality-of-life data from subjects who participated in the first MBSR program offered at Mayo Clinic. The class was taught as a collaborative effort with the University of Minnesota that had an established MBSR program. Sixteen participants completed a validated, 12-question, linear analogue self-assessment instrument, administered at the beginning and end of the program. Comparison of assessment scores using paired t-tests showed statistically significant improvement in overall quality of life (P = 0.04), mental well-being (P = 0.005), physical well-being (P < 0.001), emotional well-being (P < 0.001), level of social activity (P = .02), and spiritual well-being (P = 0.006). Although positive changes also were observed for frequency of pain, severity of pain, level of fatigue, level of support from friends and family, and financial and legal concerns, they were not statistically significant. A short intervention in the education of mindfulness significantly improved quality of life for participants.     

Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study

Background and PurposeBlood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia.MethodsThis multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03231293","term_id":"NCT03231293"}}NCT03231293).ResultsOf 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event.ConclusionsFimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.     

Community-Based Multi-Site Randomized Controlled Trial of Behavioral Activation for Patients with Depressive Disorders

Behavioral activation (BA) is a beneficial and relatively cost-effective treatment option for depression. This study utilized a pragmatic randomized controlled research design to investigate whether BA, as compared with treatment as usual (TAU), led to superior treatment effects, when delivered in community mental health settings by retrained community mental health professionals. Patients with depressive disorders (n?=?64) were randomly assigned to a 10-session BA (n?=?31) or TAU (n?=?33) group. The depressive symptoms and behavioral engagement were assessed at the baseline, post-treatment, and a six-month follow-up. Results showed that, as compared to the TAU group, the BA group had: (1) a reduction in depression severity, as evidenced by large effect sizes and greater response rates, and (2) an increase in behavioral engagement. However, the post-treatment gains were not maintained at the six-month follow-up. The implications and limitations of the study are also discussed (KCT0004098, June 27, 2019, retrospectively registered).