Prevalence of anticholinergic burden and risk factors amongst the older population: analysis of insurance claims data of Korean patients

Background Despite growing interest in the negative clinical outcomes of multiple anticholinergic use, limited studies have evaluated anticholinergic burden in the geriatric population nationally. Objective To evaluate the prevalence of high anticholinergic burden using the newly developed Korean Anticholinergic Burden Scale in comparison with previous tools and to identify associated factors. Setting National insurance data from a cross section (20%) of older Koreans (2016). Methods Anticholinergic burden was measured using the Korean scale in comparison to the Anticholinergic Drug Scale, Anticholinergic Cognitive Burden, and Anticholinergic Risk Scale. High anticholinergic burden was defined as a summed score of ≥?3 for concurrent medications or a dose-standardized average daily score of ≥?3, using each anticholinergic scale. Main outcomes measured Prevalence and predictors of high anticholinergic burden. Results Data of 1,292,323 patients were analyzed. According to the Korean scale, the prevalence of high anticholinergic burden was 25.5%. This result was similar to that from the Anticholinergic Drug Scale (24.9%) and Anticholinergic Cognitive Burden (22.2%). Factors associated with an increased likelihood of anticholinergic burden include: age, gender (female), high Charlson comorbidity index score, polypharmacy, medical aid beneficiary, co-morbidities (such as schizophrenia, depression, urinary incontinence, and Parkinson’s disease), frequent healthcare visits, various healthcare facilities utilized, and predominantly visiting hospital-level facilities. According to the Korean Anticholinergic Burden Scale, the major drugs contributing to the anticholinergic burden were ranitidine, chlorpheniramine, tramadol, and dimenhydrinate. Conclusion This study showed that 1 in 4 older Koreans are exposed to high anticholinergic burden. The predictors identified in this research might assist pharmacists in early interventions for their patients.

     

Asian plantain (Plantago asiatica) essential oils suppress 3-hydroxy-3-methyl-glutaryl-co-enzyme A reductase expression in vitro and in vivo and show hypocholesterolaemic properties in mice

Asian plantain (Plantago asiatica) essential oil (PAEO) contains multiple bioactive compounds, but its potential effects on lipid metabolism have not been examined. PAEO was found to be mostly composed of oxygenated monoterpenes, with linalool as the major component (82.5 %, w/w), measured using GC-MS. Incubation of 0-200 microg PAEO/ml with HepG2 cells for 24 h resulted in no significant toxicity. Incubation with 0.2 mg PAEO/ml altered the expression of LDL receptor (+83 %; P < 0.05) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase ( - 37 %; P < 0.05), as assessed using RT-PCR. LDL oxidation was markedly inhibited by PAEO treatment due to the prevalence of linalool compounds in PAEO. Oral administration of PAEO for 3 weeks in C57BL/6 mice significantly reduced plasma total cholesterol and TAG concentrations by 29 and 46 %, respectively. The mRNA (+58 %; P < 0.05), but not protein, levels of the LDL receptor were significantly higher, whereas both mRNA and protein levels of HMG-CoA reductase were significantly lower ( - 46 and - 11 %, respectively; P < 0.05) in the liver of PAEO-fed than of control mice. The mRNA levels of CYP7A1 were marginally reduced in HepG2 cells, but not in mouse liver after PAEO treatment. Thus, PAEO may have hypocholesterolaemic effects by altering the expression of HMG-CoA reductase. Reduced TAG and oxidised LDL may provide additional cardiovascular protective benefits.     

Influence of initial angiotensin receptor blockers on treatment persistence in uncomplicated hypertension: A nation-wide population-based study

We identified 55 504 uncomplicated, treatment-naïve hypertensive patients who started angiotensin II receptor blockers (ARBs) in 2012 from national claims data. The proportion of patients remaining on any hypertension treatment at 12 months and the adherence rate were similar between the losartan cohort (66.82% and 68.25%) and the nonlosartan ARB cohort (67.48% and 69.01%). After adjusting for confounding factors, there was no difference in persistence (aHR 0.98, 95% confidence interval (CI) 0.95–1.01) on hypertension treatment between losartan and nonlosartan ARB cohort. Post hoc analysis showed that patients initially prescribed eprosartan, irbesartan (both, aHR 1.33), and telmisartan (aHR 1.11) were more likely to discontinue the initial drug, whereas valsartan initiators (aHR 0.96) were less likely compared with losartan initiators.     

Availability and quality of emergency obstetric and neonatal care services in Afghanistan

ObjectiveTo assess the availability and utilization of emergency obstetric and neonatal care (EmONC) facilities in Afghanistan, as defined by UN indicators.MethodsIn a cross-sectional study of 78 first-line referral facilities located in secure areas of Afghanistan, EmONC service delivery was evaluated by using Averting Maternal Deaths and Disabilities (AMDD) Program assessment tools.ResultsForty-two percent of peripheral facilities did not perform all 9 signal functions required of comprehensive EmONC facilities. The study facilities delivered 17% of all neonates expected in their target populations and treated 20% of women expected to experience direct complications. The population-based rate of cesarean delivery was 1%. Most maternal deaths (96%) were due to direct causes. The direct and indirect obstetric case fatality rates were 0.8% and 0.2%, respectively.ConclusionNotable progress has been made in Afghanistan over the past 8 years in improving the quality, coverage, and utilization of EmONC services, but gaps remain. Re-examination of the criteria for selecting and positioning EmONC facilities is recommended, as is the provision of high-quality, essential maternal and neonatal health services at all levels of the healthcare system, linked by appropriate communication and functional referral systems.     

Quercetin inhibits α-MSH-stimulated melanogenesis in B16F10 melanoma cells

Quercetin is known to inhibit tyrosinase activity and melanin production in melanocytes. However, several reports suggest that quercetin has different and opposite effects on melanogenesis. This study examined the precise effects of quercetin on melanogenesis using cell‐free assay systems and melanocytes. Quercetin inhibited the monophenolase and diphenolase activities of tyrosinase, and melanin synthesis in cell‐free assay systems. Quercetin induced mild stimulation of the tyrosinase activity and dihydroxyphenylalaminechrome tautomerase (TRP‐2) expression but only at low concentrations (<20 μm ) in B16F10 melanoma cells. In contrast, the addition of 50 μm quercetin to the cells led to a significant decrease in the activity and synthesis of tyrosinase, as well as a decrease in the expression of tyrosinase‐related protein‐1 and TRP‐2 proteins, regardless of the presence or absence of α‐melanocyte stimulating hormone (α‐MSH). Quercetin also reduced the intracellular cAMP and the phosphorylated protein kinase A levels in α‐MSH‐stimulated B16F10 cells. Moreover, quercetin (20 μm ) diminished the expression and activity of tyrosinase, and melanin content in cultured normal human epidermal melanocytes. These effects were not related to its cytotoxic action. Although the in vivo effects of quercetin are still unclear, these results suggest that quercetin could play important roles in controlling melanogenesis. Copyright © 2011 John Wiley & Sons, Ltd.     

Hepatobiliary excretion of tributylmethylamonium in rats with lipopolysaccharide-induced acute inflammation

The alteration in the pharmacokinetic behaviors of organic cations (OCs) in rats during acute inflammation (Al) was investigated. Al was induced by an intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) 24 hr prior to the start of pharmacokinetic studies. Tributylmethylammonium (TBuMA) was selected as a model OC since it is largely excreted into bile, and is neither metabolized nor binds to proteins in the body. When TBuMA was administered intravenously to Al rats at a dose of 6.6 micromole/kg, the AUC was increased, while biliary excretion (i.e., cumulative amount and apparent clearance) was decreased compared to normal rats. When TBuMA was administered intravenously to Al rats at a constant rate (i.e., a bolus injection at a dose of 1.5 micromole/kg followed by a constant infusion at a rate of 1.5 micromole/kg/hr for 165 min), steady-state concentrations of plasma and liver concentrations of TBuMA were increased significantly, while in vivo hepatic uptake (amount) and canalicular excretion (clearance) were decreased. These results are consistent with a hypothesis in which both the sinusoidal uptake of TBuMA into hepatocytes via the OCT1 and the canalicular excretion of the compound from hepatocytes via the P-gp are decreased by LPS-induced Al.     

Anti-inflammatory and anti-nociceptive effects of the methanol extract of Fomes fomentarius

In an attempt to find bioactive natural products with an anti-inflammatory activity, we evaluated the effects of the methanol extract of Fomes fomentarius (MEFF) on in vivo anti-inflammatory and anti-nociceptive activities. MEFF (50, 100 mg/kg/d, p.o.) reduced acute paw edema induced by carrageenin in rats, and showed MEFF analgesic activity, as determined by an acetic acid-induced writhing test and a hot plate test in mice. To investigate the mechanism of the anti-inflammatory action of MEFF, we examined the effect of MEFF on lipopolysaccharide (LPS)-induced responses in murine macrophages cell line RAW 264.7. MEFF potently inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-alpha (TNF-alpha) in LPS-stimulated RAW 264.7 macrophages. Consistent with these observations, inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) levels were reduced by MEFF in a dose-dependent manner. Furthermore, MEFF suppressed nuclear factor-kappaB (NF-kappaB) activation in LPS-stimulated RAW 264.7 macrophages. These findings suggest that the anti-inflammatory and anti-nociceptive properties of the methanol extract of MEFF may result from the inhibition of iNOS and COX-2 expression through the down-regulation of NF-kappaB binding activity.     

N-/C-terminal deleted mutant of human endostatin efficiently acts as an anti-angiogenic and anti-tumorigenic agent

Non-collagenous (NC-1) fragments at the C-terminus of basement membrane collagen IV, XV and XIII have been implicated as negative regulators of angiogenesis. Endostatin is an endogenous carboxyl-terminal fragment of collagen XVIII/NC-1, suppressing endothelial cell proliferation, migration in vitro and tumor growth in mouse models. Endostatin can bind zinc through N- and C-terminal residues. Here we demonstrate that N-/C-terminal deleted derivative of human endostatin, H5, effectively inhibited the proliferation of human umbilical vein endothelial cells (HUVECs). Also, tube formation in vitro was comparably inhibited either by H5 or endostatin. The anti-angiogenic and anti-tumorigenic activities of H5 and endostatin were confirmed by an in vivo assay using chick chorioallantoic membrane (CAM) and mouse models, respectively. Treatment of 30 ng of H5 inhibited the capillary formation in CAM by 50%. In addition, H5 exhibited more potent anti-tumor activity than wild-type endostatin in in vivo mouse metastasis assay. These results indicate that the N-/C-terminal deletion mutant would be a strong candidate of anti-cancer agent against spontaneous tumor development and growth.     

Xylocydine, a novel inhibitor of cyclin-dependent kinases, prevents the tumor necrosis factor-related apoptosis-inducing ligand-induced apoptotic cell death of SK-HEP-1 cells

Xylocydine (4-amino-6-bromo-7-(beta-l-xylofuranosyl)pyrrolo[2,3-d]pyrimidine-5-carboxamide) blocks cyclin-dependent kinase CDK1 and CDK2/cyclin A activity in vitro (IC(50) 1.4 and 61 nM, respectively) while minimally inhibiting the three other Ser/Thr protein kinases tested (IC(50) 21-86 microM). Reduced phosphorylated nucleolin and retinoblastoma protein levels showed it also efficiently inhibited cellular CDK1 and CDK2 activity (IC(50) 50-100 and 200-500 nM, respectively). Moreover, it blocked the functional activity of CDKs in tumor necrosis factor-related apoptosis-inducing ligand-induced SK-HEP-1 cell apoptosis 20 to 1000-fold more potently than olomoucine and roscovitine. Xylocydine is thus a novel and potent CDK inhibitor that could be used to interfere with cell cycle- and apoptosis-related CDK activity in various diseases.     

Delivery modes and neonatal EEG: spatial pattern analysis

BACKGROUND: Animal studies indicate that postnatal adaptation and development of neonates could be different due to the birth method and that these effects may last throughout adulthood. STUDY DESIGN: We applied a spatio-temporal analysis to EEG recordings of a group of neonates to investigate the influence of a cesarean section on maturation and extrauterine adaptation of the brain. EEG were recorded at 2 h and at 24 h after delivery. SUBJECTS: A spectral analysis technique, the so-called Karhunen-Loeve (KL) method, was applied to EEG of 10 neonates from vaginal delivery and 17 from C-section to obtain the spatio-temporal eigenpatterns. RESULTS: Spatio-temporal analysis showed noticeable pattern differences between the two groups. Compared to the C-section, the vaginal delivered neonate's EEG recordings showed a significant increase of amplitude at Fp1 in the pattern 24 h after the delivery, but not 2 h after delivery. Dynamics in this spectral analyses were not significantly different between both groups 2 h after delivery, but the regional differences increased during the next day between both groups. CONCLUSIONS: This could come from the early insufficient complexity in C-section neonates. Global EEG complexity in C-section neonates fell short of that of vaginal delivered neonates 2 h after delivery. Many aspects of pattern change in C-section neonates followed the nature of vaginal delivered neonates. These could be considered as parts of a retarded transition of C-section neonates in the early adaptation, but some of the differences in global EEG pattern could not be explained in this way. Pattern analysis suggests that the neuronal activities of the neonatal brain are changing regionally concurrent with bi-hemispheric global dynamics. Moreover, the delivery modes could have an influence on the early postneonatal adaptation of the physiological activity in brain.