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1.
Proc Natl Acad Sci U S A ; 120(12): e2300481120, 2023 Mar 21.
Article in English | MEDLINE | ID: mdl-36913585

ABSTRACT

Graphite is one of the most chemically inert materials. Its elementary constituent, monolayer graphene, is generally expected to inherit most of the parent material's properties including chemical inertness. Here, we show that, unlike graphite, defect-free monolayer graphene exhibits a strong activity with respect to splitting molecular hydrogen, which is comparable to that of metallic and other known catalysts for this reaction. We attribute the unexpected catalytic activity to surface corrugations (nanoscale ripples), a conclusion supported by theory. Nanoripples are likely to play a role in other chemical reactions involving graphene and, because nanorippling is inherent to atomically thin crystals, can be important for two-dimensional (2D) materials in general.

2.
Nat Commun ; 12(1): 7170, 2021 Dec 09.
Article in English | MEDLINE | ID: mdl-34887395

ABSTRACT

Two-dimensional crystals with angstrom-scale pores are widely considered as candidates for a next generation of molecular separation technologies aiming to provide extreme, exponentially large selectivity combined with high flow rates. No such pores have been demonstrated experimentally. Here we study gas transport through individual graphene pores created by low intensity exposure to low kV electrons. Helium and hydrogen permeate easily through these pores whereas larger species such as xenon and methane are practically blocked. Permeating gases experience activation barriers that increase quadratically with molecules' kinetic diameter, and the effective diameter of the created pores is estimated as ∼2 angstroms, about one missing carbon ring. Our work reveals stringent conditions for achieving the long sought-after exponential selectivity using porous two-dimensional membranes and suggests limits on their possible performance.

3.
Zhonghua Yi Xue Za Zhi ; 100(13): 1023-1027, 2020 Apr 07.
Article in Chinese | MEDLINE | ID: mdl-32294861

ABSTRACT

Objective: To investigate the electrophysiological features of patients with subacute combined degeneration (SCD). Methods: The electrophysiological data of 85 hospitalized patients in Department of Neurology, First Medical Centre, Chinese PLA General Hospital from January 2014 to September 2018 were retrospectively analyzed. Results: Abnormality rate of motor nerve conduction (27.4%(93/339)) was lower than that of sensory nerve conduction (45.9%(107/233)) (P<0.001). Abnormality of sensory nerve action potential amplitude was more frequent than conduction velocity abnormality (22.7%(53/233) vs 4.7%(11/233), P=0.001). Abnormality rate of needle electromyogram (EMG) was higher in lower limbs than upper limbs (31.9%(59/185) vs 5.7%(5/87), P<0.001). Spontaneous potentials were unrelated to disease duration or severity. Abnormal somatosensory evoked potential (SEP) results appeared more frequent in lower limbs (80.8%(118/146)) than upper limbs (61.1%(77/126)) (P<0.001). SEP abnormalities (71.7%(195/272)) were more common than nerve conduction abnormalities (35.0%(200/572)). Abnormal findings presented in 15/16 of visual evoked potential (VEP) studies. Neurological severity score were correlated with electrophysiological findings. Conclusions: Posterior funiculus is more likely to be affected than peripheral nerves in SCD patients. The sensory nerves rather than motor nerves, lower limbs rather than upper limbs, axons of sensory nerves rather than myelin, are more severely affected. Electrophysiological tests can provide evidence in early diagnosis, lesions location, and disease severity evaluation for SCD.


Subject(s)
Subacute Combined Degeneration , Electromyography , Evoked Potentials, Somatosensory , Evoked Potentials, Visual , Humans , Neural Conduction , Retrospective Studies
4.
Nat Commun ; 10(1): 4243, 2019 Sep 18.
Article in English | MEDLINE | ID: mdl-31534140

ABSTRACT

Defect-free monolayers of graphene and hexagonal boron nitride are surprisingly permeable to thermal protons, despite being completely impenetrable to all gases. It remains untested whether small ions can permeate through the two-dimensional crystals. Here we show that mechanically exfoliated graphene and hexagonal boron nitride exhibit perfect Nernst selectivity such that only protons can permeate through, with no detectable flow of counterions. In the experiments, we use suspended monolayers that have few, if any, atomic-scale defects, as shown by gas permeation tests, and place them to separate reservoirs filled with hydrochloric acid solutions. Protons account for all the electrical current and chloride ions are blocked. This result corroborates the previous conclusion that thermal protons can pierce defect-free two-dimensional crystals. Besides the importance for theoretical developments, our results are also of interest for research on various separation technologies based on two-dimensional materials.

6.
Nanoscale ; 9(1): 251-257, 2017 Jan 07.
Article in English | MEDLINE | ID: mdl-27906401

ABSTRACT

The large surface roughness, low work function and high cost of transparent electrodes using multilayer graphene films can limit their application in organic photovoltaic (OPV) cells. Here, we develop single layer graphene (SLG) films as transparent anodes for OPV cells that contain light-absorbing layers comprised of the evaporable molecular organic semiconductor materials, zinc phthalocyanine (ZnPc)/fullerene (C60), as well as a molybdenum oxide (MoOx) interfacial layer. In addition to an increase in the optical transmittance, the SLG anodes had a significant decrease in surface roughness compared to two and four layer graphene (TLG and FLG) anodes fabricated by multiple transfer and stacking of SLGs. Importantly, the introduction of a MoOx interfacial layer not only reduced the energy barrier between the graphene anode and the active layer, but also decreased the resistance of the SLG by nearly ten times. The OPV cells with the structure of polyethylene terephthalate/SLG/MoOx/CuI/ZnPc/C60/bathocuproine/Al were flexible, and had a power conversion efficiency of up to 0.84%, which was only 17.6% lower than the devices with an equivalent structure but prepared on commercial indium tin oxide anodes. Furthermore, the devices with the SLG anode were 50% and 86.7% higher in efficiency than the cells with the TLG and FLG anodes. These results show the potential of SLG electrodes for flexible and wearable OPV cells as well as other organic optoelectronic devices.

8.
Nanoscale ; 8(20): 10714-23, 2016 May 19.
Article in English | MEDLINE | ID: mdl-27153523

ABSTRACT

The relatively high sheet resistance, low work function and poor compatibility with hole injection layers (HILs) seriously limit the applications of graphene as transparent conductive electrodes (TCEs) for organic light emitting diodes (OLEDs). Here, a graphene oxide/graphene (GO/G) vertical heterostructure is developed as TCEs for high-performance OLEDs, by directly oxidizing the top layer of three-layer graphene films with ozone treatment. Such GO/G heterostructure electrodes show greatly improved optical transmittance, a large work function, high stability, and good compatibility with HIL materials (MoO3 in this work). Moreover, the conductivity of the heterostructure is not sacrificed compared to the pristine three-layer graphene electrodes, but is significantly higher than that of pristine two-layer graphene films. In addition to high flexibility, OLEDs with different emission colors based on the GO/G heterostructure TCEs show much better performance than those based on indium tin oxide (ITO) anodes. Green OLEDs with GO/G heterostructure electrodes have the maximum current efficiency and power efficiency, as high as 82.0 cd A(-1) and 98.2 lm W(-1), respectively, which are 36.7% (14.8%) and 59.2% (15.0%) higher than those with pristine graphene (ITO) anodes. These findings open up the possibility of using graphene for next generation high-performance flexible and wearable optoelectronics with high stability.

9.
Br J Dermatol ; 175(6): 1290-1300, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27146027

ABSTRACT

BACKGROUND: Superficial basal cell carcinoma (sBCC) can be safely treated topically. Potentially noninvasive imaging techniques, such as optical coherence tomography (OCT), may be useful to diagnose and manage patients with sBCC and obviate the need for biopsy. OBJECTIVES: To evaluate in OCT (i) the sensitivity and specificity for sBCC diagnosis, (ii) the accuracy in determining BCC depth and (iii) the role in management of sBCC mimickers. METHODS: A prospective, consecutive cohort of lesions for which sBCC was considered in the differential diagnosis. These lesions underwent clinical, dermoscopic and OCT assessment. Diagnosis and its confidence were recorded for each modality and were correlated with the histopathological diagnosis (punch biopsy). Interpretation of the OCT images and assessment of individual features were performed blinded to the biopsy results. RESULTS: In total, 168 lesions were recruited: 52% were sBCC, 26% were other BCC variants and the remaining lesions were actinic keratosis, squamous cell carcinoma in situ, other benign inflammatory processes and two other malignant tumours. The sensitivity and specificity of OCT for diagnosis of sBCC were 0·87 and 0·80, respectively. There was excellent correlation between OCT and biopsy for tumour depth amongst tumours ≤ 0·4 mm (Pearson correlation r = 0·86, P < 0·001), but the correlation was less as depth increased (Pearson correlation r = 0·71, P < 0·001 for all tumours < 1·0 mm). CONCLUSIONS: OCT has good diagnostic accuracy for diagnosing sBCC and measuring depth in tumours ≤ 0·4 mm. Potentially OCT can reduce the need for biopsy in clinically suspected sBCCs. However, careful follow-up is required in such cases as there is a small risk (5%) of misdiagnosis.


Subject(s)
Carcinoma, Basal Cell/diagnostic imaging , Skin Neoplasms/diagnostic imaging , Adult , Aged , Aged, 80 and over , Carcinoma, Basal Cell/pathology , Female , Humans , Male , Middle Aged , Observer Variation , Prospective Studies , Sensitivity and Specificity , Skin Neoplasms/pathology , Tomography, Optical Coherence/standards , Tumor Burden
10.
Bull Entomol Res ; 105(5): 555-65, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26138927

ABSTRACT

Arginine kinase (AK) is an important regulation factor of energy metabolism in invertebrate. An arginine kinase gene, named HaAK, was identified to be differentially expressed between Cry1Ac-susceptible (96S) and Cry1Ac-resistant (Bt-R) Helicoverpa armigera larvae using cDNA-amplification fragment length polymorphism analysis. The full-length open reading frame sequence of HaAK gene with 1068 bp was isolated from H. armigera. Quantitative reverse transcription polymerase chain reaction assay revealed that HaAK gene is specifically expressed in multiple tissues and at larval developmental stages. The peak expression level of HaAK was detected in the midgut of the fifth-instar larvae. Moreover, the expression of HaAK was obviously down-regulated in Bt-R larvae. We further constructed a dsRNA vector directly targeting HaAK and employed RNAi technology to control the larvae. The feeding bioassays showed that minute quantities of dsRNA could greatly increase the larval mortality and delay the larval pupation. Silencing of HaAK significantly retarded the larval development, indicating that HaAK is a potential target for RNA interference-based pest management.


Subject(s)
Arginine Kinase/metabolism , Gene Expression Regulation, Developmental/physiology , Gene Expression Regulation, Enzymologic/physiology , Moths/growth & development , RNA Interference , Animals , Arginine Kinase/genetics , Larva/growth & development , Larva/metabolism , Moths/metabolism
11.
Br J Dermatol ; 173(6): 1371-80, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26211438

ABSTRACT

Optical coherence tomography (OCT) is a noninvasive imaging tool used in vivo in real time for diagnosis, treatment delineation and monitoring of basal cell carcinoma (BCC). Features of BCC on OCT have been widely described and reviewed. However, the diagnostic accuracy of OCT in these various applications is unclear. We systematically reviewed the literature to assess the accuracy of OCT in diagnosis and management of BCC using the Embase and Medline databases. In total 179 unique references were identified in the initial search, of which 22 studies with 556 histologically proven BCCs were eligible. Assessment of the quality of eligible studies was undertaken using the STROBE criteria. Data extraction and quality assessment were performed independently by the two authors. This systematic review provides an overview of the clinical applications of OCT in the diagnosis and management of BCC. OCT has been suggested to be useful in the diagnosis, treatment planning and treatment monitoring of BCC. As the technology improves and its utility increases, further studies with good methodological quality will be needed to implement OCT into daily practice.


Subject(s)
Carcinoma, Basal Cell/pathology , Skin Neoplasms/pathology , Tomography, Optical Coherence/methods , Adult , Aged , Aged, 80 and over , Carcinoma, Basal Cell/therapy , Humans , Male , Middle Aged , Observer Variation , Sensitivity and Specificity , Skin Neoplasms/therapy , Treatment Outcome
12.
J Hum Hypertens ; 28(2): 85-91, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24048294

ABSTRACT

We examined the contribution of arterial wave reflection to early abnormalities in left ventricular relaxation, whether this association was modified by gender or hypertension and the role of reflected wave timing and amplitude. We studied a cohort of normotensive and untreated essential hypertensive Taiwanese participants (675 men, 601 women, mean age 52 years). Doppler flow and applanation tonometry were performed to assess carotid-femoral pulse wave velocity (PWV) and augmentation index (AI). Diastolic parameters including the ratio between the peak velocity of early and late diastolic mitral inflow (E/A), E-deceleration time and left atrial (LA) diameter were measured by echocardiography. In multivariate models predicting E/A, women were more likely to have lower E/A than men (ß=-0.08, P<0.001). AI was significantly associated with lower E/A in both men (ß=-0.09, P=0.005) and women (ß=-0.12, P<0.001) independent of PWV. Inclusion of AI in the overall model reduced the gender difference in E/A by 61% and rendered it nonsignificant. There was a significant interaction between AI and hypertension (P=0.02). The inverse association between AI and E/A was significant only in normotensive men and women, and only for the amplitude but not timing of the reflected wave. In conclusion, the contribution of wave reflection to left ventricular diastolic dysfunction was independent of arterial stiffness, more pronounced in normotensive individuals and explained a significant portion of the gender difference in diastolic function.


Subject(s)
Blood Pressure , Hypertension/complications , Hypertension/physiopathology , Vascular Stiffness , Ventricular Dysfunction, Left/etiology , Ventricular Function, Left , Adult , Aged , Chi-Square Distribution , Cross-Sectional Studies , Diastole , Female , Humans , Hypertension/diagnosis , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prognosis , Pulse Wave Analysis , Risk Factors , Sex Factors , Stroke Volume , Taiwan , Time Factors , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/physiopathology
13.
Clin Lab ; 59(7-8): 869-74, 2013.
Article in English | MEDLINE | ID: mdl-24133918

ABSTRACT

BACKGROUND: To establish a tacrolimus-induced diabetes rat model and assess efficacy and safety of insulin glargine combined with repaglinide in Chinese patients with diabetes after liver transplantation. METHODS: Animal experiments and clinical trial were conducted. Animal experiments: Male SD rats were randomly divided into tacrolimus (4 mg/kg daily) and control group (saline). Rats were sacrificed after five months of treatment and blood was collected through heart puncture. Patients who underwent liver transplantation were selected and followed up regularly. If HbA1c was < 9%, repaglinide was administered; if HbA1c was > or = 9%, glargine plus repaglinide was administered. RESULTS: For rat model studies, in the tacrolimus group, fasting blood glucose (FBG) levels were increased after three months (p < 0.01). After five months, the insulin secretion index and the sensitivity index in the tacrolimus group was significantly lower than in the control group (p < 0.01). For studies of post-transplant diabetes mellitus (PTDM), eighty-six liver transplant recipients were enrolled. 51 were given repaglinide and 35 were given repaglinide combined with glargine. After treatment for 1, 6, and 12 months, FBG, post-prandial blood glucose (PPBG), and HbA1c levels decreased (p < 0.05) in both groups, and no statistically significant changes were observed in the liver and kidney function indicators (p > 0.05). No severe hypoglycemia episodes were reported. CONCLUSIONS: Tacrolimus caused islet cell necrosis, reduced insulin secretion, increased insulin resistance, and increased blood glucose in the model. The blood glucose levels increased in a time-dependent manner. Combination of glargine and repaglinide was effective and safe for Chinese patients with post liver transplant diabetes mellitus.


Subject(s)
Diabetes Mellitus/etiology , Immunosuppressive Agents/adverse effects , Liver Transplantation/adverse effects , Tacrolimus/adverse effects , Animals , Blood Glucose/analysis , Male , Rats , Rats, Sprague-Dawley
14.
J Hum Hypertens ; 27(3): 204-10, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22551938

ABSTRACT

Central aortic systolic blood pressure (SBP-C) can be estimated from a cuff oscillometric waveform derived during the pulse volume plethysmography (PVP) by applying a device-specific aortic pressure-to-PVP waveform-generalized transfer function (A2P(GTF)). The present study compared the performance of an aortic-to-brachial pressure waveforms generalized transfer function (A2B(GTF)), which is independent of any PVP devices, with an A2P(GTF). Generalized transfer function of aortic-to-brachial (A2B(GTF)) and aortic-to-PVP (A2P(GTF)) were generated from the simultaneously obtained central aortic and brachial pressure waveforms recorded by a high-fidelity dual pressure sensor catheter, and the PVP waveform recorded by a customized noninvasive blood pressure monitor during cardiac catheterization in 40 patients, and were then applied in another 100 patients with simultaneously recorded invasive aortic pressure and noninvasively calibrated (using cuff SBP and diastolic blood pressures) PVP waveforms. The mean difference±s.d. between the noninvasively estimated and invasively recorded SBP-C was -2.1±7.7 mm Hg for A2B(GTF), which was not greater than that of -3.0±7.7 mm Hg for A2P(GTF) (P<0.01). In conclusion, SBP-C can be measured reliably using a noninvasive blood pressure monitor by applying either an A2P(GTF) or A2B(GTF) to a noninvasively calibrated PVP waveform. The performance of an A2B(GTF) is not inferior to that of an A2P(GTF).


Subject(s)
Aorta/physiopathology , Blood Pressure Determination/instrumentation , Blood Pressure , Brachial Artery/physiopathology , Transducers, Pressure , Aged , Blood Pressure Determination/standards , Calibration , Equipment Design , Female , Humans , Male , Middle Aged , Oscillometry/instrumentation , Plethysmography , Predictive Value of Tests , Reproducibility of Results , Systole , Transducers, Pressure/standards
15.
J Hum Hypertens ; 25(11): 665-71, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21150931

ABSTRACT

The effects of pressure wave reflection have been incompletely described by the central augmentation index (cAI) and augmented pressure (Pa). We therefore investigated the determinants of amplitude of the reflected wave (Pb), which is independent of the reflected wave transit time (RWTT) and has been shown to predict cardiovascular mortality in the general population. A total of 180 (117 men, mean age 68 years old) patients were recruited. Carotid pressure waveforms derived by tonometry at baseline and 3 min after administration of sublingual nitroglycerin (NTG) were calibrated and then decomposed into the forward and backward waves to yield Pb. The ratio of pre-ejection period/ejection time (PEP/ET) was measured. By stepwise multivariate analysis, independent determinants of Pb included brachial mean blood pressure (ß=0.56, P<0.001), heart rate (ß=-0.29, P<0.001), age (ß=0.20, P<0.001), PEP/ET (ß=-0.16, P=0.004) and height (ß=-0.13, P=0.018). RWTT, body mass index and sex were significant independent determinants of Pa and cAI but did not contribute to Pb. Change of Pb but not Pa or cAI significantly predicted the changes of carotid systolic (r=0.550, P<0.001) and pulse pressure (r=0.618, P<0.001) after NTG. In conclusion, determinants of Pb differ from those of cAI and Pa. Pb is independent of sex and RWTT.


Subject(s)
Blood Pressure , Brachial Artery/physiology , Carotid Arteries/physiology , Administration, Sublingual , Aged , Aged, 80 and over , Ankle Brachial Index , Blood Pressure/drug effects , Brachial Artery/drug effects , Carotid Arteries/drug effects , Electrocardiography , Female , Humans , Linear Models , Male , Manometry , Middle Aged , Nitroglycerin/administration & dosage , Phonocardiography , Predictive Value of Tests , Sex Factors , Stroke Volume , Taiwan , Time Factors , Vasodilator Agents/administration & dosage , Ventricular Function, Left
16.
Br J Radiol ; 83(988): e83-5, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20335438

ABSTRACT

CT-guided transthoracic lung biopsy is becoming a widely accepted procedure for the diagnosis of pulmonary lesions. The rate of severe complications following such a procedure has been reported. Of these complications, air embolism is the most likely to be fatal. We report a case of right coronary air embolism resulting in myocardial infarction after a CT-guided percutaneous needle biopsy of the lung. The patient died from underlying malignant disease 4 months later.


Subject(s)
Biopsy, Needle/adverse effects , Coronary Vessels , Embolism, Air/etiology , Lung Neoplasms/pathology , Lung/pathology , Myocardial Infarction/etiology , Adult , Aorta , Biopsy, Needle/methods , Embolism, Air/diagnostic imaging , Fatal Outcome , Humans , Male , Radiography, Interventional , Tomography, X-Ray Computed
17.
Autoimmun Rev ; 7(6): 431-4, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18558357

ABSTRACT

Natural autoantibodies are normal components of the humoral arm of the immune system found in clinically healthy individuals. There are two subpopulations of natural antibodies, including an overt group of antibodies that are readily detected in unfractionated normal human sera. The other natural antibody subgroup is revealed by physico or biochemical treatment of normal human sera in vitro. Unmasking of this latter cryptic natural autoantibodies (cNA) may occur in vivo by local factors in the tissue environment of disease states. The masking cryptic factors may be immunoglobulin (Ig) or non-Ig in nature. These factors may either be co-inhibitors or co-enhancers of cNA. In the heat-potentiated binding of natural anti-phospholipid antibodies, apolipoprotein H (beta 2-glycoprotein I) appears to act as a co-enhancer. The immuno-relationship between the in vitro and in vivo cNA phenomenon remains to be elucidated.


Subject(s)
Autoantibodies/immunology , Antibodies, Anticardiolipin/blood , Antibodies, Anticardiolipin/immunology , Autoantibodies/blood , Autoantibodies/classification , Humans , beta 2-Glycoprotein I/metabolism
18.
Nano Lett ; 8(12): 4191-5, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19367961

ABSTRACT

Vertically aligned Mg-doped GaN nanorods have been epitaxially grown on n-type Si substrate to form a heterostructure for fabricating p-n heterojunction photovoltaic cells. The p-type GaN nanorod/n-Si heterojunction cell shows a well-defined rectifying behavior with a rectification ratio larger than 10(4) in dark. The cell has a high short-circuit photocurrent density of 7.6 mAlcm2 and energy conversion efficiency of 2.73% under AM 1.5G illumination at 100 mW/cm2. Moreover, the nanorod array may be used as an antireflection coating for solar cell applications to effectively reduce light loss due to reflection. This study provides an experimental demonstration for integrating one-dimensional nanostructure arrays with the substrate to directly fabricate heterojunction photovoltaic cells.

19.
J Neurosci ; 27(18): 4870-81, 2007 May 02.
Article in English | MEDLINE | ID: mdl-17475795

ABSTRACT

Cannabinoids modulate energy homeostasis and decrease cognitive arousal, possibly by acting on hypothalamic neurons including those that synthesize melanin-concentrating hormone (MCH) or hypocretin/orexin. Using patch-clamp recordings, we compared the actions of cannabinoid agonists and antagonists on identified MCH or hypocretin neurons in green fluorescent protein-expressing transgenic mice. The cannabinoid type-1 receptor (CB1R) agonist R-(+)-[2,3-dihydro-5-methyl-3-(4-morpho linylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN55,212,2) depolarized MCH cells and increased spike frequency; in contrast, WIN55,212,2 hyperpolarized and reduced spontaneous firing of the neighboring hypocretin cells, both results consistent with reduced activity seen with intracerebral cannabinoid infusions. These effects were prevented by AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], a CB1R antagonist, and by tetrodotoxin, suggesting no postsynaptic effect on either neuron type. In MCH cells, depolarizing WIN55,212,2 actions were abolished by the GABA(A) receptor antagonist bicuculline, suggesting that the CB1R-mediated depolarization was attributable to reduced synaptic GABA release. WIN55,212,2 decreased spontaneous IPSCs, reduced the frequency but not amplitude of miniature IPSCs, and reduced electrically evoked synaptic currents in MCH cells. Glutamate microdrop experiments suggest that WIN55,212,2 acted on axons arising from lateral hypothalamus local inhibitory cells that innervate MCH neurons. In hypocretin neurons, the reduced spike frequency induced by WIN55,212,2 was attributable to presynaptic attenuation of glutamate release; CB1R agonists depressed spontaneous and evoked glutamatergic currents and reduced the frequency of miniature EPSCs. Cannabinoid actions on hypocretin neurons were abolished by ionotropic glutamate receptor antagonists. Together, these results show that cannabinoids have opposite effects on MCH and hypocretin neurons. These opposing actions could help explain the increase in feeding and reduction in arousal induced by cannabinoids.


Subject(s)
Arousal/drug effects , Cannabinoids/pharmacology , Eating/drug effects , Hypothalamic Hormones/agonists , Hypothalamus/drug effects , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Melanins/agonists , Neuropeptides/antagonists & inhibitors , Pituitary Hormones/agonists , Action Potentials/drug effects , Action Potentials/physiology , Animals , Arousal/physiology , Benzoxazines/pharmacology , Eating/physiology , Hypothalamic Hormones/physiology , Hypothalamus/physiology , Intracellular Signaling Peptides and Proteins/physiology , Melanins/physiology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Morpholines/pharmacology , Naphthalenes/pharmacology , Neurons/drug effects , Neurons/physiology , Neuropeptides/physiology , Orexins , Pituitary Hormones/physiology
20.
Eur J Clin Invest ; 37(3): 197-206, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17359487

ABSTRACT

BACKGROUND: Familial hypercholesterolaemia (FH) is characterized by very high serum cholesterol and premature coronary atherosclerosis. Arterial stiffness and atherosclerosis are two major underlying pathophysiologies of arterial disease that are predictive of future cardiovascular events. The aims of this study were to quantify atherosclerosis and arterial stiffness and to evaluate their relationship with high sensitive C-reactive protein (hs-CRP) and the level of exposure to high serum cholesterol in FH patients. MATERIALS AND METHODS: We measured traditional risk factors, hs-CRP, intima-media thickness (IMT) of carotid artery, and brachial-ankle pulse wave velocity (baPWV) in 35 heterozygous FH subjects and 17 healthy control subjects. Cholesterol-year score (CYS) was calculated to estimate the lifetime cholesterol burden in FH subjects. RESULTS: FH subjects had significantly elevated total cholesterol, low-density lipoprotein cholesterol, and carotid IMT compared with those without mutations. Among FH patients, the baPWV and carotid IMT were higher in cases with high cholesterol burden than those without. Similarly, the baPWV and carotid IMT were also higher in cases with elevated hs-CRP (> 1 mg L(-1)) than those without. Multiple linear regression analysis demonstrated CYS and hs-CRP were significant independent predictors of baPWV and IMT in FH patients. CONCLUSIONS: Both high cholesterol burden and vascular inflammation are not only associated with atherosclerosis, but also contribute to the development of arterial stiffness in FH patients. Early detection of hypercholesterolaemia in FH patients is warranted to prevent the untoward pathophysiologies.


Subject(s)
Atherosclerosis/genetics , C-Reactive Protein/physiology , Hypercholesterolemia/genetics , Adult , Atherosclerosis/physiopathology , Case-Control Studies , Elasticity , Female , Humans , Hypercholesterolemia/physiopathology , Male , Pedigree , Risk Factors , Tunica Intima/physiopathology , Vascular Resistance/physiology
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