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1.

Study Objectives:

Reports on the association of polymorphisms in the gene encoding apolipoprotein E (APOE)—a vital macromolecule in cholesterol metabolism—with obstructive sleep apnea (OSA) have provided conflicting results. Our objective was to meta-analytically synthesize the existing evidence for the association of the APOE ε4 allele with the risk of OSA.

Design:

Random effects meta-analysis and meta-regression

Setting:

Genetic epidemiological studies reporting the association of APOE ε4 allele with OSA susceptibility.

Patients or Participants:

Synthesis of APOE ε4 allele data from 6,508 subjects including 1,901 cases of OSA and 4,607 controls.

Interventions:

None

Measurements and Results:

Eight studies were included in the random effects meta-analysis; the summary effect size measured as odds ratio (OR) for association of the APOE ε4 allele with the risk of OSA was found to be 1.13 (95% confidence interval 0.86–1.47). There was a statistically significant heterogeneity (I2 = 72%, P = 0.001) across study results that was not explained by the mean age, proportion of males, or the proportion possessing the APOE ε4 allele or when grouped based on the geographic location of the study.

Conclusions:

The hypothesis that the APOE ε4 allele may be causally associated with OSA cannot be supported on the basis of published literature.

Citation:

Thakre TP; Mamtani MR; Kulkarni H. Lack of association of the APOE ε4 allele with the risk of obstructive sleep apnea: meta-analysis and meta-regression. SLEEP 2009;32(11):1507-1511.  相似文献   

2.

Purpose

The aim of this study was to examine the effects of all-trans retinoic acid (ATRA) on diabetic nephropathy.

Materials and Methods

We measured amounts of urinary albumin excretion (UAE) after administrating ATRA to Otsuka Long-Evans Tokushima Fatty (OLETF) rats. In order to understand the mechanism of action for ATRA, we administrated ATRA to examine its inhibitory action on the production of transforming growth factor-β1 (TGF-β1), protein kinase C (PKC), and reactive oxidative stress (ROS) in cultured rat mesangial cells (RMCs).

Results

After 16 weeks of treatment, UAE was lower in the ATRA-treated OLETF rats than in the non-treated OLETF rats (0.07±0.03 mg/mgCr vs. 0.17±0.15 mg/mgCr, p<0.01). After incubation of RMCs in media containing 30 or 5 mM of glucose, treatment with ATRA showed time- and dose-dependent decreases in TGF-β1 levels and ROS. Moreover, ATRA treatment showed a dose-dependent decrease in PKC expression.

Conclusion

ATRA treatment suppressed UAE and TGF-β1 synthesis, which was mediated by significant reductions in PKC activity and ROS production. Our results suggest that ATRA has a potential therapeutic role for diabetic nephropathy.  相似文献   

3.

Objective

To observe the discrepancies of responses induced by Schistosoma japonicum (S. japonicum) normal cercaria antigen (NCA) and ultraviolet (UV) -radiation-attenuated cercaria antigen (UVACA) in an in vitro system.

Methods

S. japonicum cercariae were collected and UVACA and NCA were prepared. Mouse macrophage model cells (RAW 264.7) were treated with medium, NCA (40 µg/mL) or UVACA (40 µg/mL) in the presence or absence of recombinant mouse interferon gamma (rmIFN-γ; 4 ng/mL) for 48 h. Cell surface staining and flow cytometry were used to assess the major histocompatibility complex (MHC)γ; 4 ng/mL) for 48 h. Cell surface staining and flow cytometry were used to assess the major histocompatibility complex (MHC) II expression, and data were expressed as mean fluorescence intensities (MFI). Interleukin (IL) -10, IL-6 and prostaglandin E2 (PGE2) in cell culture supernatant were evaluated by commercial enzyme-linked immunosorbent assays.

Results

NCA significantly suppressed IFN-γ-induced MHC II expression on RAW 264.7 cells. In the presence of IFN-γ, NCA significantly promoted IL-6, IL-10 and PGE2 secretion from RAW 264.7 cells. In the presence of IFN-γ, UVACA significantly promoted IL-10 but not IL-6 and PGE2 secretion from RAW 264.7 cells and showed no effect on IFN-γ-induced MHC II expression. Compared with UVACA, NCA significantly suppressed IFN-γ-induced MHC II expression and significantly promoted IL-6, PGE2 and IL-10 secretion from RAW 264.7 cells.

Conclusion

RAW 264.7 cells respond differently to NCA and UVACA. NCA can significantly suppress IFN-γ-induced MHC II expression and significantly promote IL-6, IL-10 and PGE2 secretion from RAW 264.7 cells compared with UVACA.  相似文献   

4.

Background

Flowers of Bauhinia kockiana were investigated for their anticancer properties.

Methods

Gallic acid (1), and methyl gallate (2), were isolated via bioassay-directed isolation, and they exhibited anticancer properties towards several cancer cell lines, examined using MTT cell viability assay. Pyrogallol (3) was examined against the same cancer cell lines to deduce the bioactive functional group of the phenolic compounds.

Results

The results showed that the phenolic compounds could exhibit moderate to weak cytotoxicity towards certain cell lines (GI50 30 – 86 µM), but were inactive towards DU145 prostate cancer cell (GI50 > 100 µM).

Conclusion

It was observed that pyrogallol moiety was one of the essential functional structures of the phenolic compounds in exhibiting anticancer activity. Also, the carboxyl group of compound 1 was also important in anticancer activity. Examination of the PC-3 cells treated with compound 1 using fluorescence microscopy showed that PC-3 cells were killed by apoptosis.  相似文献   

5.

Background

The antioxidant properties of ethanolic root extract of pepper fruit (Donnetia tripetala), and its effect on lipid peroxidation of some fresh beef tissues during frozen storage were investigated.

Materials and Methods

The antioxidant parameters were assessed using standard methods, while malondialdehyde levels of different fresh beef tissue sections treated with the extract prior to freezing, were estimated in a colorimetric reaction with thiobarbituric acid.

Results

The H2O2-scavenging ability of the extract was similar to that of ascorbic acid, with a maximum scavenging power of 55.61 ±4.98%, and an IC50 value of 86µg/ml. The extract exhibited a concentration-dependent ferric ion-reducing power, although this was significantly lower relative to that of the ascorbic acid (p < 0.05). The total phenolic content was 212.5 ± 0.002 mg/g, while the nitric oxide-scavenging ability was 64.33 ± 0.2% after 150 min. The capacity of the extract to inhibit lipid peroxidation in frozen heart muscle slices was significantly higher than that of vitamin C (p < 0 .05), but comparable to vitamins C and E in frozen testes and kidney slices.

Conclusion

These results suggest that the root extract of D. tripetala is rich in antioxidants which can be applied to meat preservation during refrigerated storage.  相似文献   

6.

Background

Ficus species are used in African traditional medicine in the treatment of a wide variety of ailments and diseases such as convulsive disorder, wound healing, gonorrhea, tuberculosis, diabetes, diarrhoeal infections, dysentery, malaria and HIV. The aim of this study was to isolate the phytochemical constituents in the plant and test them for their antibacterial activity.

Materials and methods

The fruits, leaves and stem bark were extracted with organic solvents and the compounds in the extracts separated and purified by column chromatography before being identified by NMR spectroscopy and by comparison of the NMR data against values reported in the literature. The antibacterial activity of the pure compounds and extracts were tested using the disk diffusion method.

Results

Three triterpenes and three flavonoids: lupeol acetate (1); cycloart-23-ene-3,25-diol (2); β-sitosterol (3); 5,7,4′-trihydroxyflavan-3-ol (4); epicatechin (5); and isovitexin (6) were isolated in this study. Antimicrobial activity was observed at 8 mg mL−1 for Staphylococcus aureus ATCC 29213 with four of the six isolated compounds, with no activity being observed at 1 – 4 mg mL−1 against Escherichia coli ATCC 25922, E. coli ATCC 35218 and S. aureus ATCC 43300. Epicatechin (5) was found to decrease adhesion of E. coli ATCC 25922 and S. aureus ATCC 29213. Decreased adhesion of S. aureus ATCC 29213 was also observed with 5,7,4′-trihydroxyflavan-3-ol (4) and isovitexin (6).

Conclusions

The results of this study provide baseline information on F. sansibarica''s potential validity in the treatment of infections associated with Gram-positive microorganisms.  相似文献   

7.

Study Objectives:

Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. It is associated with motor deficits, sleep disturbances, and cognitive impairment. The pathology associated with PD and the effects of sleep deprivation impinge, in part, upon common molecular pathways suggesting that sleep loss may be particularly deleterious to the degenerating brain. Thus we investigated the long-term consequences of sleep deprivation on short-term memory using a Drosophila model of Parkinson disease.

Participants:

Transgenic strains of Drosophila melanogaster.

Design:

Using the GAL4-UAS system, human α-synuclein was expressed throughout the nervous system of adult flies. α-Synuclein expressing flies (αS flies) and the corresponding genetic background controls were sleep deprived for 12 h at age 16 days and allowed to recover undisturbed for at least 3 days. Short-term memory was evaluated using aversive phototaxis suppression. Dopaminergic systems were assessed using mRNA profiling and immunohistochemistry.

Measurments and Results:

When sleep deprived at an intermediate stage of the pathology, αS flies showed persistent short-term memory deficits that lasted ≥ 3 days. Cognitive deficits were not observed in younger αS flies nor in genetic background controls. Long-term impairments were not associated with accelerated loss of dopaminergic neurons. However mRNA expression of the dopamine receptors dDA1 and DAMB were significantly increased in sleep deprived αS flies. Blocking D1-like receptors during sleep deprivation prevented persistent short-term memory deficits. Importantly, feeding flies the polyphenolic compound curcumin blocked long-term learning deficits.

Conclusions:

These data emphasize the importance of sleep in a degenerating/reorganizing brain and shows that pathological processes induced by sleep deprivation can be dissected at the molecular and cellular level using Drosophila genetics.

Citation:

Seugnet L; Galvin JE; Suzuki Y; Gottschalk L; Shaw PJ. Persistent short-term memory defects following sleep deprivation in a drosophila model of parkinson disease. SLEEP 2009;32(8):984-992.  相似文献   

8.

Purpose

Inadequate empirical therapy for severe infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBLEC) is associated with poor outcomes. This study was designed to investigate risk factors for community-onset ESBLEC bacteremia at admission to a tertiary care hospital.

Materials and Methods

A case-control study was performed that included all episodes of ESBLEC bacteremia in the outpatient department or within 48 hours of admission from January 2005 to March 2009. Data on predisposing factors were collected. The molecular epidemiology of ESBLEC clinical isolates was also determined.

Results

Among 25281 blood cultures, 60 episodes of ESBLEC bacteremia were studied, which accounted for 7% of all E. coli bacteremia at admission. Healthcare-associated infection [odds ratio (OR), 8.3; 95% confidence interval (CI), 2.4-28.7; p=0.001], malignancy (OR, 4.6; 95% CI, 1.3-16.3; p=0.018), urinary tract infection (OR, 139.1; 95% CI, 24.6-788.2; p<0.001), hepatobiliary infection (OR, 79.1; 95% CI, 13.5-463.8; p<0.001), third generation cephalosporin usage during preceding 3 months (OR, 16.4; 95% CI, 2.0-131.8; p=0.008), and severe sepsis/septic shock (OR, 73.7; 95% CI, 12.4-438.5; p<0.001) were determined as independent risk factors for community-onset ESBLEC bacteremia. The most common extended-spectrum β-lactamase (ESBL) gene identified was blaCTX-M-15 (n=31) followed by blaCTX-M-14 (n=23).

Conclusion

The most common types of ESBLs in E. coli causing community-onset bacteremia were CTX-M-15 and CTX-M-14 in Korea. By result of decision tree analysis, the empirical use of carbapenems is suggested only for patients with severe sepsis/septic shock, hepatobiliary infection, or healthcare-associated urinary tract infection.  相似文献   

9.
10.

Background

A great revival of scientific interests in drug discovery has been witnessed in recent years from medicinal plants for health maintenance. The aim of this work was to investigate three Nigerian medicinal plants collected in Nigeria for their in vitro antiplasmodial and antimicrobial activities.

Materials and Methods

Extracts obtained from parts of Persea americana, Jatropha podagrica and Picralima nitida and their fractions were evaluated for in vitro antiprotozoal and antimicrobial activity.

Result

The methanol extract of P. nitida demonstrated activity against chloroquine-sensitive and chloroquine-resistant P. falciparum clones with IC50 values of 6.3 and 6.0 µg/mL, respectively. Methanol and chloroform extracts of P. americana seed showed antifungal activity against Cryptococcus neoformans IC50 less than 8 and 8.211 µg/mL respectively. Finally, the petroleum ether extract of P. americana had activity against methicillin-resistant Staphylococcus aureus (MRSA) with an IC50 value of 8.7 µg/mL.

Conclusion

The study revealed the antibacterial and antiplasmodial activities of the plants extracts at the tested concentrations.  相似文献   

11.

Background

A number of medicinal plants and there compounds played a major role in the treatment of hepatic disorders. They were widely used for the treatment of these disorders, and oxidant stress injury was one of the liver injury mechanisms. The present study evaluated the antioxidant activity and the hepatoprotective effect of each extracts of Phlomis maximowiczii.

Materials and Methods

The antioxidant activity was assayed by the methods of ABTS, FRAP and DPPH in vitro. Hepatoprotective effect of P. maximowiczii extracts was examined using carbon tetrachloride-induced acute liver injury in mice.

Results

P. maximowiczii n-butanol (PMBU) extract, ABTS (IC50=18.96 µg/mL), DPPH (IC50=25.15 µg/mL), and FRAP (RACT50=2775.6±144.18 µmol/g), showed higher scavenging capacity than that of P. maximowiczii ethyl acetate (PMEA). The n-butanol extract could significantly reduce the level of GPT, GOT and MDA (P<0.05, P<0.001 and P<0.001, respectively) and increase the level of SOD (P<0.001), respectively.

Conclusion

The antioxidant activity of n-butanol extract in vitro was related with the level of MDA and SOD in vivo, and hepatoprotective effect of n-butanol extract also had relationship with its antioxidant activity in vivo.  相似文献   

12.

Study Objectives:

Respiratory and heart rate variability exhibit fractal scaling behavior on certain time scales. We studied the short-term and long-term correlation properties of heartbeat and breathing-interval data from disease-free subjects focusing on the age-dependent fractal organization. We also studied differences across sleep stages and night-time wake and investigated quasi-periodic variations associated with cardiac risk.

Design:

Full-night polysomnograms were recorded during 2 nights, including electrocardiogram and oronasal airflow.

Setting:

Data were collected in 7 laboratories in 5 European countries.

Participants:

180 subjects without health complaints (85 males, 95 females) aged from 20 to 89 years.

Interventions:

None.

Measurements and Results:

Short-term correlations in heartbeat intervals measured by the detrended fluctuation analysis (DFA) exponent α1 show characteristic age dependence with a maximum around 50–60 years disregarding the dependence on sleep and wake states. Long-term correlations measured by α2 differ in NREM sleep when compared with REM sleep and wake, besides weak age dependence. Results for respiratory intervals are similar to those for α2 of heartbeat intervals. Deceleration capacity (DC) decreases with age; it is lower during REM and deep sleep (compared with light sleep and wake).

Conclusion:

The age dependence of α1 should be considered when using this value for diagnostic purposes in post-infarction patients. Pronounced long-term correlations (larger α2) for heartbeat and respiration during REM sleep and wake indicate an enhanced control of higher brain regions, which is absent during NREM sleep. Reduced DC possibly indicates an increased cardiovascular risk with aging and during REM and deep sleep.

Citation:

Schumann AY; Bartsch RP; Penzel T; Ivanov PC; Kantelhardt JW. Aging effects on cardiac and respiratory dynamics in healthy subjects across sleep stages. SLEEP 2010;33(7):943-955.  相似文献   

13.

Purpose

Myeloid differentiation-2 (MD-2) has been associated with endotoxin and inflammatory disorders because it can recognize lipopolysaccharide (LPS) binding and attenuate Toll-like receptor 4 (TLR4)-mediated signaling. However, its role in allergic inflammation has yet to be clarified. We examined whether single nucleotide polymorphisms (SNPs) in MD-2 promoter can affect MD-2 expression and aimed to clarify the relationship between Der p 2 allergy and SNPs of MD-2 promoter.

Methods

The function of SNPs of MD-2 promoter and the effects of cytokines and immunoglobulin on the secretion and mRNA expression were investigated in 73 allergic subjects with different MD-2 gene promoter variants. Peripheral blood mononuclear cells were cultured with or without LPS in the presence of Dermatophagoides pteronyssinus group 2 allergen (Der p 2), followed by mRNA extraction and cytokine expression analysis. The culture supernatants were collected for cytokine measurement.

Results

Patients with the MD-2 promoter SNPs (rs1809441/rs1809442) had increased mRNA expressions of MD-2, ε heavy chain of IgE (Cε), and interleukin (IL)-8; however, only MD-2 and IL-8 were further up-regulated after Der p 2 stimulation. Patients with SNPs of MD-2 promoter tended to have high levels of IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α after Der p 2 and LPS stimulation. Increased secretions of IL-6, IL-8, and IL-10 were found to be up-regulated by Der p 2 stimulation, and an increased secretion of IFN-γ and decreased secretion of IL-4 were noted after LPS stimulation.

Conclusions

The high levels of proinflammatory cytokines secreted by Der p 2 were predetermined by MD-2 promoter SNPs (rs1809441/rs1809442). Through cytokine secretion by Der p 2 and LPS, these SNPs may serve as an indicator of the pathological phenotype of Der p 2-induced allergic inflammation.  相似文献   

14.

Background

Momordica charantia L. is a medicinal plant commonly used in the management of diabetes mellitus.

Objectives

We investigated the blood glucose lowering effect of the methanolic fruit extract of the Ugandan variety of M. charantia L. in alloxan-induced diabetic albino rats.

Methods

500g of M. charantia powder were macerated in methanol and the extract administered to two groups of alloxan-induced diabetic rats. The first group received 125mg/kg, the second 375mg/kg and a third group 7mg/kg of metformin. A fourth group received 1ml normal saline. Fasting blood glucose (FBG) levels were measured at 0.5,1,2,3,5,8 and 12 hours and compared using one-way ANOVA.

Results

There was an initial rise in FBG for 1 hour after administration of extracts followed by steep reductions. Significant reduction in FBG occurred at 2 hours for 125mg/kg of extract (−3.2%, 313±25.9 to 303±25.0mg/dL, p = 0.049), 375mg/kg of extract (−3.9%, 356±19.7 to 342±20.3mg/dL, p = 0.001), and metformin (−2.6%, 344±21.7 to 335±21.1mg/dL, p = 0.003) when compared to normal saline. The maximum percentage reduction in FBG by both extracts occurred between 3 and 12 hours post dose.

Conclusions

The methanolic fruit extract of M. charantia exhibits dose dependent hypoglycaemic activity in vivo.  相似文献   

15.
16.
17.

Purpose

Although follicular thyroid cancer (FTC) has a relatively fair prognosis, distant metastasis sometimes results in poor prognosis and survival. There is little understanding of the mechanisms contributing to the aggressiveness potential of thyroid cancer. We showed that hypoxia inducible factor-1α (HIF-1α) induced aggressiveness in FTC cells and identified the underlying mechanism of the HIF-1α-induced invasive characteristics.

Materials and Methods

Cells were cultured under controlled hypoxic environments (1% O2) or normoxic conditions. The effect of hypoxia on HIF-1α, and epithelial-to-mesenchymal transition (EMT) related markers were evaluated by quantitative real-time PCR, Western blot analysis and immunocytochemistry. Invasion and wound healing assay were conducted to identify functional character of EMT. The involvement of HIF-1α and Twist in EMT were studied using gene overexpression or silencing. After orthotopic nude mouse model was established using the cells transfected with lentiviral shHIF-1α, tissue analysis was done.

Results

Hypoxia induces HIF-1α expression and EMT, including typical morphologic changes, cadherin shift, and increased vimentin expression. We showed that overexpression of HIF-1α via transfection resulted in the aforementioned changes without hypoxia, and repression of HIF-1α with RNA interference suppressed hypoxia-induced HIF-1α and EMT. Furthermore, we also observed that Twist expression was regulated by HIF-1α. These were confirmed in the orthotopic FTC model.

Conclusion

Hypoxia induced HIF-1α, which in turn induced EMT, resulting in the increased capacity for invasion and migration of cells via regulation of the Twist signal pathway in FTC cells. These findings provide insight into a possible therapeutic strategy to prevent invasive and metastatic FTC.  相似文献   

18.

Study Objectives:

To investigate if sudden-onset motor-behavioral episodes in REM sleep behavior disorder (RBD) are associated with phasic events of REM sleep, and to explore the potential meaning of such an association.

Design:

Observational review analysis.

Setting:

Tertiary sleep center.

Patients:

Twelve individuals (11 males; mean age 67.6 ± 7.4 years) affected by idiopathic RBD, displaying a total of 978 motor-behavioral episodes during nocturnal in-laboratory video-PSG.

Interventions:

N/A

Measurements and Results:

The motor activity displayed was primitive in 69.1% and purposeful/semi-purposeful in 30.9% of the motor-behavioral episodes recorded. Sleeptalking was significantly more associated with purposeful/semi-purposeful motor activity than crying and/or incomprehensible muttering (71.0% versus 21.4%, P < 0.005). In 58.2% of the motor-behavioral episodes, phasic EEG-EOG events (rapid eye movements [REMs], α bursts, or sawtooth waves [STWs]) occurred simultaneously. Each variable (REMs, STWs, α bursts) was associated more with purposeful/semi-purposeful than with primitive movements (P < 0.05).

Conclusions:

Motor-behavioral episodes in RBD were significantly more likely to occur in association with phasic than with tonic periods of REM sleep. The presence of REMs, α bursts and STWs was found to be more frequent in more complex episodes. We hypothesize that motor-behavioral episodes in RBD are likely to occur when the brain, during REM sleep, is in a state of increased instability (presence of α bursts) and experiencing stronger stimulation of visual areas (REMs).

Citation:

Manni R; Terzaghi M; Glorioso M. Motor-behavioral episodes in REM sleep behavior disorder and phasic events during REM sleep. SLEEP 2009;32(2):241–245.  相似文献   

19.
20.

Introduction

The purpose of this study was to compare the clinical, microbiological and immunological effects of subgingival irrigation with Dentol and 0.2% chlorhexidine in human advanced periodontitis.

Material and methods

Twenty cases of advanced periodontitis patients were randomly treated either with Dentol (as test) or 0.2% chlorhexidine (as control) every other day for 29 days after primary scaling, root planing and oral hygiene instruction. Pocket depth (PD), bleeding on probing (BOP) and plaque index (PI) were considered as clinical parameters. Total counts of aerobic and anaerobic bacteria were measured in subgingival plaque. At the end, concentrations of TNF-α and IL-1β in gingival crevicular fluid were measured as inflammatory markers.

Results

PD and BOP decreased in both groups on the 29th day and two weeks afterward. PI did not show any statistical difference either within or among groups (p > 0.05). Results indicate that both chlorhexidine and Dentol diminished total count of subgingival anaerobic bacteria significantly (p < 0.05). Total count of subgingival aerobic bacteria increased in both groups, but the differences between the two groups were statistically significant in favour of Dentol (p < 0.05). The level of IL-1β in the crevicular fluid was reduced in both groups but it was more significant in the test group (p < 0.05). The TNF-a level decreased in both groups but the statistical difference between the two groups was negligible (p > 0.05).

Conclusions

Subgingivally irrigation with Dentol, containing 0.02% carvacrol, every other day for 29 days is equally or more effective than 0.2% chlorhexidine in reducing clinical and immunological inflammatory indices.  相似文献   

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