Resveratrol Inhibits Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Pathological Neovascularization

Purpose

To investigate the effects of resveratrol on the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human adult retinal pigment epithelial (ARPE-19) cells, and on experimental choroidal neovascularization (CNV) in mice.

Materials and Methods

ARPE-19 cells were treated with different concentrations of resveratrol and then incubated under hypoxic conditions with subsequent evaluation of cell viability, expression of HIF-1α, and expression of VEGF. The effects of resveratrol on the synthesis and degradation of hypoxia-induced HIF-1α were evaluated using inhibitors of the PI3K/Akt/mTOR and the ubiquitin proteasome pathways. In animal studies, CNV lesions were induced in C57BL/6 mice by laser photocoagulation. After 7 days of oral administration of resveratrol or vehicle, which began one day after CNV induction, image analysis was used to measure CNV areas on choroidal flat mounts stained with isolectin IB4.

Results

In ARPE-19 cells, resveratrol significantly inhibited HIF-1α and VEGF in a dose-dependent manner, by blocking the PI3K/Akt/mTOR signaling pathway and by promoting proteasomal HIF-1α degradation. In mice experiments, orally administered resveratrol significantly inhibited CNV growth in a dose-dependent manner.

Conclusion

Resveratrol may have therapeutic value in the management of diseases involving pathological neovascularization.     

Hypoxia Induces Epithelial-Mesenchymal Transition in Follicular Thyroid Cancer: Involvement of Regulation of Twist by Hypoxia Inducible Factor-1α

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.     

Effect of carbon dioxide pneumoperitoneum on human renal cell carcinoma proliferation and metastasis in an orthotropic xenograft nude mouse model

Introduction

This study aimed to explore the effect of carbon dioxide (CO₂) pneumoperitoneum on tumor proliferation and metastasis in an orthotropic xenograft nude mice model of human renal cell carcinoma (RCC) and evaluate the safety of CO₂ pneumoperitoneum laparoscopy for treating RCC.

Material and methods

RCC 786-0 cells were injected to establish an orthotropic xenograft model. Fifty nude mice were given orthotropic inoculations and randomized to five groups: group A (control); group B (CO₂ pneumoperitoneum for 2 h); group C (CO₂ pneumoperitoneum for 4 h); group D (CO₂ pneumoperitoneum for 4 h and 24 h after waking); group E (CO₂ pneumoperitoneum for 4 h and 48 h after waking). The proliferation status was observed in RCC specimens by immunohistochemical staining for Ki67. The protein levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were examined by western blotting.

Results

All groups showed similar Ki67-positive staining in RCC samples (p > 0.05). The relative expression of HIF-1α and VEGF gradually increased in both group B and group C, as compared with group A, but only the difference between group C and group A reached statistical significance (p < 0.05). The protein levels of HIF-1α and VEGF decreased in both group D and group E, as compared with group B and group C; however, the differences between group D, group E, and group A did not reach statistical significance (p > 0.05).

Conclusions

In an orthotropic xenograft nude mice model of RCC, CO₂ pneumoperitoneum has no effect on expression of the cellular proliferation marker Ki67. However, CO₂ pneumoperitoneum rapidly induces transient expression of HIF-1α and VEGF. Thus, CO₂ pneumoperitoneum laparoscopy may be a safe method for treating RCC.     

Effects of Diet-Induced Mild Obesity on Airway Hyperreactivity and Lung Inflammation in Mice

Purpose

Obesity has been suggested to be linked to asthma. However, it is not yet known whether obesity directly leads to airway hyperreactivity (AHR) or obesity-induced airway inflammation associated with asthma. We investigated obesity-related changes in adipokines, AHR, and lung inflammation in a murine model of asthma and obesity.

Materials and Methods

We developed mouse models of chronic asthma via ovalbumin (OVA)-challenge and of obesity by feeding a high-fat diet, and then performed the methacholine bronchial provocation test, and real-time PCR for leptin, leptin receptor, adiponectin, adiponectin receptor (adipor1 and 2), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) β, and tumor necrosis factor (TNF) α in lung tissue. We also measured cell counts in bronchoalveolar lavage fluid.

Results

Both obese and lean mice chronically exposed to OVA developed eosinophilic lung inflammation and AHR to methacholine. However, obese mice without OVA challenge did not develop AHR or eosinophilic inflammation in lung tissue. In obese mice, lung mRNA expressions of leptin, leptin receptor, VEGF, TGF, and TNF were enhanced, and adipor1 and 2 expressions were decreased compared to mice in the control group. On the other hand, there were no differences between obese mice with or without OVA challenge.

Conclusion

Diet-induced mild obesity may not augment AHR or eosinophilic lung inflammation in asthma.     

Alpha thalassemia among sickle cell anaemia patients in Kampala,Uganda

Background

Sickle cell anaemia is prevalent in sub Saharan Africa. While α+-thalassaemia is known to modulate sickle cell anaemia, its magnitude and significance in Uganda have hitherto not been described.

Objectives

To determine the prevalence of α+thalassaemia among sickle cell anaemia patients in Mulago Hospital and to describe the clinical and laboratory findings in these patients.

Methods

A cross sectional study was carried out on patients with sickle cell anaemia in Kampala. Dried blood spots were used to analyze for the deletional α+ thalassaemia using multiplex polymerase chain reaction.

Results

Of the 142 patients with sickle cell anaemia, 110 (77.5%) had the αα+thalassaemia deletion. The gene frequency of (−α) was 0.425. Ninety one percent (100/110) of those with α+thalassaemia were heterozygous (αα/α-). Amongst the patients older than 60 months, 15 (83.3%) of those without αα+thalassaemia had significant hepatomegaly of greater than 4 cm compared to 36 (45.6%) of those with α+thalassaemia (p=0.003).

Conclusion

The gene frequency of (−α) of 0.425 noted in this study is higher than that reported from many places in Africa. Concurrent alpha thalassemia might be a protective trait against significant hepatomegaly in sickle cell anaemia patients more than 60 months of age at Mulago hospital.     

Administration of Pigment Epithelium-Derived Factor Inhibits Airway Inflammation and Remodeling in Chronic OVA-Induced Mice via VEGF Suppression

Purpose

Pigment epithelium-derived factor (PEDF) is a recently discovered antiangiogenesis protein. PEDF possesses powerful anti-inflammatory, antioxidative, antiangiogenic, and antifibrosis properties. It has been reported that PEDF can regulate vascular endothelial growth factor (VEGF) expression. This study aimed to evaluate whether recombinant PEDF protein could attenuate allergic airway inflammation and airway remodeling via the negative regulation of VEGF using a murine model of chronic ovalbumin (OVA)-induced asthma and BEAS-2B human bronchial epithelial cells.

Methods

In an in vivo experiment, mice sensitized with OVA were chronically airway challenged with aerosolized 1% OVA solution for 8 weeks. Treated mice were given injections of recombinant PEDF protein (50 or 100 µg/kg body weight) via the tail vein. In an in vitro experiment, we investigated the effects of recombinant PEDF protein on VEGF release levels in BEAS-2B cells stimulated with IL-1β.

Results

Recombinant PEDF protein significantly inhibited eosinophilic airway inflammation, airway hyperresponsiveness, and airway remodeling, including goblet cell hyperplasia, subepithelial collagen deposition, and airway smooth muscle hypertrophy. In addition, recombinant PEDF protein suppressed the enhanced expression of VEGF protein in lung tissue and bronchoalveolar lavage fluid (BALF) in OVA-challenged chronically allergic mice. In the in vitro experiment, VEGF expression was increased after IL-1β stimulation. Pretreatment with 50 and 100 ng/mL of recombinant PEDF protein significantly attenuated the increase in VEGF release levels in a concentration-dependent manner in BEAS-2B cells stimulated by IL-1β.

Conclusions

These results suggest that recombinant PEDF protein may abolish the development of characteristic features of chronic allergic asthma via VEGF suppression, providing a potential treatment option for chronic airway inflammation diseases such as asthma.     

Cyclooxygenase-2 and vascular endothelial growth factor in chronic hepatitis,cirrhosis and hepatocellular carcinoma

Background/Aims

Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are up-regulated in hepatocellular carcinoma (HCC). To investigate the levels of COX-2 and VEGF expression in chronic hepatitis (CH), cirrhosis, and HCC.

Methods

The immunohistochemical expressions of COX-2 and VEGF were evaluated in tissues from patients with CH (n=95), cirrhosis (n=38), low-grade HCC (LG-HCC; n=6), and high-grade HCC (HG-HCC; n=29).

Results

The COX-2 expression scores in CH, cirrhosis, LG-HCC, and HG-HCC were 3.3±1.9 (mean±SD), 4.2±1.7, 5.5±1.0, and 3.4±2.4, respectively (CH vs. cirrhosis, P=0.016; CH vs. LG-HCC, P=0.008; LG-HCC vs. HG-HCC, P=0.004), and the corresponding VEGF expression scores were 0.9±0.8, 1.5±0.7, 1.8±0.9, and 1.6±1.1 (CH vs. cirrhosis, P<0.001; CH vs. LG-HCC, P=0.011; LG-HCC vs. HG-HCC, P=0.075). Both factors were correlated with the fibrosis stage in CH and cirrhosis (COX-2: r=0.427, P<0.001; VEGF: r=0.491, P<0.001). There was a significant correlation between COX-2 and VEGF in all of the tissue samples (r=0.648, P<0.001), and between high COX-2 and VEGF expression scores and survival (COX-2: P=0.001; VEGF: P<0.001).

Conclusions

The expressions of both COX-2 and VEGF are significantly higher in cirrhosis and LG-HCC than in CH. High COX-2 and high VEGF expressions are associated with a high survival rate.     

HIF-1α Upregulation due to Depletion of the Free Ubiquitin Pool

Hypoxia-inducible factor 1alpha (HIF-1α), which transactivates a variety of hypoxia-induced genes, is rapidly degraded under nomoxia through the hydroxylation-ubiquitination-proteasome pathway. In this study, we addressed how HIF-1α is stabilized by proteasome inhibitors. The ubiquitin pool was rapidly reduced after proteasome inhibition, followed by the accumulation of non-ubiquitinated HIF-1α. The poly-ubiquitination of HIF-1α was resumed by restoration of free ubiquitin, which suggests that the HIF-1α stabilization under proteasome inhibition is attributed to depletion of the free ubiquitin pool. Ni²⁺ and Zn²⁺ also stabilized HIF-1α with depletion of the free ubiquitin pool and these effects of metal ions were attenuated by restoration of free ubiquitin. Ni²⁺ and Zn²⁺ may disturb the recycling of free ubiquitin, as MG132 does. Based on these results, the state of the ubiquitin pool seems to be another critical factor determining the cellular level of HIF-1α.

Graphical Abstract

相似文献   

Immunolocalization of VEGF, VEGFR-1 and VEGFR-2 in lung tissues after acute hemorrhage in rats

In treatment of hypovolemia it is important to reestablish normal tissue hemodynamics after fluid resuscitation. Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) have been identified as important in many physiological and pathological processes. In this study, we aimed to investigate the histo-physiological effects of VEGF, VEGFR-1 (flt-1) and VEGFR-2 (KDR/flk-1) in resuscitation with different plasma substitutes on lung tissues after acute hemorrhage in rats. Male Sprague-Dawley rats (n=25) were used in this study. The left femoral vein and artery were cannulated for the administration of volume expanders and for direct measurement of mean arterial blood pressure (MAP) (Power-Lab) and heart rate (HR). Fifteen rats were bled (5 ml/10 min) and infused (5 ml/5 min) with one of three randomly selected fluids: (a) dextran-70 (Macrodex); (b) gelatin (Gelofusine); or (c) physiological saline (PS, 0.9% isotonic saline) solutions. Five rats were bled and none were infused (hypovolemia group) and five rats were untreated as the control group. At the end of the experiment, rats were sacrificed and lung tissues were removed for routine processing and paraffin wax embedding. Sections of tissue were stained with hematoxylin and eosin (H&E) and selected blocks were then prepared for indirect immunohistochemical labeling for anti-VEGF, anti-VEGFR-1 and anti-VEGFR-2 primary antibodies. It was observed that both MAP and HR decreased parallel to blood withdrawn in this time interval. The MAP and HR were restored in the following periods. In the control rats, positive immunoreactivity of VEGF and its receptors (VEGFR-1 and VEGFR-2) were detected in respiratory epithelial cells, respiratory and vascular smooth muscle cells, alveolar cells and endothelial cells. While strong immunoreactivities of VEGF and VEGFR-1 were observed in the hypovolemia group, only moderate immunoreactivity of VEGFR-2 was seen in this group. Moderately strong immunolabeling of VEGF and VEGFR-1 were observed in the dextran-70, gelatin and PS resuscitated groups, whereas only weak immunolabeling of VEGFR-2 was observed in these groups. In summary, the vascular protecting effects of these factors were observed with fluid resuscitation, contributing to the pathophysiological changes seen in hypovolemia.     

Empirical Evidence for “Syndrome Z”: A Hierarchical 5-Factor Model of the Metabolic Syndrome Incorporating Sleep Disturbance Measures

Study Objective:

Sleep disturbances have been associated with individual components of the metabolic syndrome (“syndrome X”), and, although the concept has been proposed, it is not known whether sleep disturbances actually cluster with features of the metabolic syndrome to produce a unifying trait, “syndrome Z”. Therefore, we evaluated a second-order factor model, whereby syndrome Z was described by 5 first-order factors – insulin resistance, obesity, hypertension, dyslipidemia, and sleep disturbance – with the sleep disturbance factor defined using the apnea-hypopnea index, arousal index, percentage of sleep time with oxygen saturation less than 90%, and percentage of slow wave sleep.

Design:

Observational, cross-sectional study.

Setting:

Clinical research center.

Participants:

Five hundred thirty-three adults from the Cleveland Family Sleep Study who underwent polysomnography and were not treated by continuous positive airway pressure.

Measurements and Results:

When modeling syndrome Z as a second-order factor unifying 5 first-order factors, we observed good overall model fit (χ²/df = 3.20; CFI = 0.96; RMSEA = 0.06; SRMR = 0.05) and found that obesity was the most important determining factor (standardized loading = 0.85 ± standard error = 0.02; P < 0.01) followed by sleep disturbance (0.82 ± 0.03; P < 0.01), insulin resistance (0.67 ± 0.03; P < 0.01), hypertension (0.64 ± 0.04; P < 0.01), and dyslipidemia (0.60 ± 0.05; P < 0.01). Simultaneous multiple group analyses revealed that this model was essentially generalizable across age, race, and sex subgroups.

Conclusions:

Our results demonstrate that sleep disturbance co-aggregates with other metabolic features to represent a single unifying trait, syndrome Z. Although our model awaits validation in other populations, it provides a tool for better understanding the synergistic risk of syndrome Z, compared with syndrome X, on type 2 diabetes and cardiovascular disease in future studies.

Citation:

Nock NL; Larkin EK; Patel SR; Redline S. Empirical evidence for “Syndrome Z”: a hierarchical 5-factor model of the metabolic syndrome incorporating sleep disturbance measures. SLEEP 2009;32(5):615-622.     

Fermented Ginseng Improves the First-Night Effect in Humans

Study Objectives:

The goal of this study was to clarify whether ginseng fermented by lactic acid bacteria (fermented ginseng, FG), can improve the first-night effect (FNE) in humans.

Design:

Behavioral tests and quantification of mRNA expression related to GABAergic neurotransmission in brain (glutamic acid decarboxylase 1, γ-aminobutyrate aminotransferase [Abat], γ-aminobutyric acid transporter 1 [GAT1], γ-aminobutyric acid transporter 4, γ-aminobutyric acid A receptor subunit α 1 and γ-aminobutyric acid A receptor subunit α 2) were carried out in FG-treated mice. We also performed double-blind sleep recordings of human subjects given FG or placebo.

Setting:

A university-based sleep laboratory.

Patients or Participants:

Sixteen healthy male volunteers (aged 20.69 ± 0.44 years) were observed in the human study.

Interventions:

At the end of administration, 2 consecutive all-night polysomnography recordings were performed. Subjects also completed psychological questionnaires, and urine and saliva samples were taken to analyze stress-sensitive markers.

Measurements and Results:

The light-dark transition test demonstrated that FG had some anxiolytic effect in mice, but other anxiety measures were unaffected. The hippocampal mRNA expression showed a decrease of Abat and GAT1 suggesting an increase of GABA. Other regions (amygdala and cerebellum) showed no differences. Furthermore, there was some evidence (using simple pairwise comparisons but not supported in the full ANOVA model) that administration of FG tended to diminish decreases in total sleep time and sleep efficiency (seen as first night effects in the placebo group) without affecting sleep architecture.

Conclusions:

Our results suggest the administration of FG could improve the FNE in humans. The improvement may be related to an anxiolytic effect of FG which acts via GABAergic modification.

Citation:

Kitaoka K; Uchida K; Okamoto N; Chikahisa S; Miyazaki T; Takeda E; Séi H. Fermented ginseng improves the first-night effect in humans. SLEEP 2009;32(3):413–421.     

Phytoestrogen α-zearalanol ameliorates memory impairment and neuronal DNA oxidation in ovariectomized mice

OBJECTIVE:

The aim of this study was to evaluate the effect of a novel phytoestrogen, α-Zearalanol, on Alzheimer''s disease-related memory impairment and neuronal oxidation in ovariectomized mice.

METHODS:

Female C57/BL6 mice were ovariectomized or received sham operations and treatment with equivalent doses of 17β-estradiol or α-Zearalanol for 8 weeks. Their spatial learning and memory were analyzed using the Morris water maze test. The antioxidant enzyme activities and reactive oxygen species generation, neuronal DNA oxidation, and MutT homolog 1 expression in the hippocampus were measured.

RESULTS:

Treatment with 17β-estradiol or α-Zearalanol significantly improved spatial learning and memory performance in ovariectomized mice. In addition, 17β-estradiol and α-Zearalanol attenuated the decrease in antioxidant enzyme activities and increased reactive oxygen species production in ovariectomized mice. The findings indicated a significant elevation in hippocampi neuronal DNA oxidation and reduction in MutT homolog 1 expression in estrogen-deficient mice, but supplementation with 17β-estradiol or α-Zearalanol efficaciously ameliorated this situation.

CONCLUSION:

These results demonstrate that α-Zearalanol is potentially beneficial for improving memory impairments and neuronal oxidation damage in a manner similar to that of 17β-estradiol. Therefore, the compound may be a potential therapeutic agent that can ameliorate neurodegenerative disorders related to estrogen deficiency.     

Polyunsaturated fatty acids augment tumoricidal action of 5-fluorouracil on gastric cancer cells by their action on vascular endothelial growth factor,tumor necrosis factor-α and lipid metabolism related factors

Introduction

Gastric cancer is the second most common cause of cancer-related mortality worldwide. 5-fluorouracil (5-FU) is a commonly used anti-cancer drug. Various polyunsaturated fatty acids (PUFAs) are known to have tumoricidal action both in vitro and in vivo. Though PUFAs are known to augment the cytotoxic action of anti-cancer drugs, the exact mechanism is not clear.

Material and methods

The human gastric cancer cell line MGC (undifferentiated) and human gastric cancer cell line SGC (semi-differentiated) were either 5-FU alone or a combination of 5-FU + PUFAs and their proliferation, and ability to secrete tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) and lipid metabolism-related factors lipoprotein lipase (LPL), peroxisome proliferator-activated-γ (PPAR-γ), and CCAAT enhancer-binding protein (C/EBP) were investigated and analyzed.

Results

It was noted that combined treatment of 5-FU + PUFAs on gastric carcinoma (MGC and SGC) cells produced a significant growth inhibitory action compared with either agent alone by inhibiting the production of TNF-α and VEGF and a simultaneous increase in the expression of LPL, PPAR-γ, and C/EBP.

Conclusions

Based on the results of the present study, it is concluded that PUFAs enhance the tumoricidal action of the anti-cancer drug 5-FU by acting on anti-angiogenic factors and enzymes involved in lipid metabolism.     

Chlamydophila pneumoniae enhances secretion of VEGF, TGF-�� and TIMP-1 from human bronchial epithelial cells under Th2 dominant microenvironment

Purpose

Chlamydophila pneumoniae infection in the airways is thought to be associated with the pathogenesis of asthma, especially in non-atopic severe asthma with irreversible airway obstruction that may be related to airway remodeling. Here, we investigated whether C. pneumoniae infection enhances the secretion of critical chemical mediators for airway remodeling, such as VEGF, TGF-β, and TIMP-1, in human bronchial epithelial cells (BECs) in a Th2-dominant microenvironment.

Methods

Human bronchial epithelial cells (BEAS-2B cells) were infected with C. pneumoniae strain TW183 and cultured in both a Th1-dominant microenvironment with INF-γ and a Th2-dominant microenvironment with IL-4 or IL-13 added to the culture medium. The VEGF, TGF-β, and TIMP-1 levels in the culture supernatants were measured using enzyme-linked immunosorbent assays (ELISA). The activation of NF-κB in each experimental condition was determined using an electrophoretic mobility shift assay.

Results

Chlamydophila pneumoniae-infected BECs showed enhanced secretion of VEGF, TGF-β, and TIMP-1 compared with non-infected BECs. The levels of cytokines secreted from BECs were increased more when IL-13 was added to the culture medium. C. pneumoniae-infected BECs also showed increased NF-κB activation.

Conclusions

These results suggest that C. pneumoniae plays a role in the pathogenesis of airway remodeling in asthma, revealing a Th2-dominant immune response. Further studies are required to clarify the precise mechanism of C. pneumoniae infection in airway remodeling.     

The expression of adiponectin receptors and the effects of adiponectin and leptin on airway smooth muscle cells

Purpose

Obesity is a major risk factor for asthma and it influences airway smooth muscle function and responsiveness. Adiponectin is inversely associated with obesity and its action is mediated through at least 2 cell membrane receptors (AdipoR1 and AdipoR2). Leptin is positively associated with obesity. We investigated whether human airway smooth muscle (ASM) cells express adiponectin receptors and whether adiponectin and leptin regulate human ASM cell proliferation and vascular endothelial growth factor (VEGF) release.

Materials and Methods

Human ASM cells were growth-arrested in serum-deprived medium for 48 hours and then stimulated with PDGF, adiponectin and leptin. After 48 hours of stimulation, proliferation was determined using a cell proliferation ELISA kit. Human AdipoR1 and -R2 mRNA expressions were determined by RT-PCR using human-specific AdipoR1 and -R2 primers. Concentrations of VEGF, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1α in cell culture supernatant were determined by ELISA.

Results

Both AdipoR1 and AdipoR2 mRNA were expressed in the cultured human ASM cells. However, adiponectin did not suppress PDGF-enhanced ASM cell proliferation, nor did leptin promote ASM cell proliferation. Leptin promoted VEGF release by human ASM cells, while adiponectin did not influence VEGF release. Neither leptin nor adiponectin influenced MCP-1 secretion from human ASM cells. Adiponectin and MIP-1α were not secreted by human ASM cells.

Conclusion

Human ASM cells expressed adiponectin receptors. However, adiponectin did not regulate human ASM cell proliferation or VEGF release, while leptin stimulated VEGF release by human ASM cells.     

Motor-Behavioral Episodes in REM Sleep Behavior Disorder and Phasic Events During REM Sleep

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.