Moving beyond 90% Carbon Capture by Highly Selective Membrane Processes.

A membrane-based system with a retentate recycle process in tandem with an enriching cascade was studied for >90% carbon capture from coal flue gas. A highly CO2-selective facilitated transport membrane (FTM) was utilized particularly to enhance the CO2 separation efficiency from the CO2-lean gases for a high capture degree. A techno-economic analysis showed that the retentate recycle process was advantageous for ≤90% capture owing to the reduced parasitic energy consumption and membrane area. At >90% capture, the enriching cascade outperformed the retentate recycle process since a higher feed-to-permeate pressure ratio could be applied. An overall 99% capture degree could be achieved by combining the two processes, which yielded a low capture cost of USD47.2/tonne, whereas that would be USD 42.0/tonne for 90% capture. This FTM-based approach for deep carbon capture and storage can direct air capture for the mitigation of carbon emissions in the energy sector.

Effects of treatment processes on AOC removal and changes of bacterial diversity in a water treatment plant.

The effectiveness of different treatment processes on assimilable organic carbon (AOC) removal and bacterial diversity variations was evaluated in a water treatment plant. The van der Kooij technique was applied for AOC analysis and responses of bacterial communities were characterized by the metagenomics assay. Results show that the AOC concentrations were about 93, 148, 43, 51, 37, and 38 µg acetate-C/L in effluents of raw water basin, preozonation, rapid sand filtration (RSF), ozonation, biofiltration [biological activated carbon (BAC) filtration], and chlorination (clear water), respectively. Increased AOC concentrations were observed after preozonation, ozonation, and chlorination units due to the production of biodegradable organic matters after the oxidation processes. Results indicate that the oxidation processes were the main causes of AOC formation, which resulted in significant increases in AOC concentrations (18-59% increment). The AOC removal efficiencies were 47, 28, and 60% in the RSF, biofiltration, and the whole system, respectively. RSF and biofiltration were responsible for the AOC treatment and both processes played key roles in AOC removal. Thus, both RSF and biofiltration processes would contribute to AOC treatment after oxidation. Sediments from the raw water basin and filter samples from RSF and BAC units were collected and analyzed for bacterial communities. Results from scanning electron microscope analysis indicate that bacterial colonization was observed in filter materials. This indicates that the surfaces of the filter materials were beneficial to bacterial growth and AOC removal via the adsorption and biodegradation mechanisms. Next generation sequencing analyses demonstrate that water treatment processes resulted in the changes of bacterial diversity and community profiles in filters of RSF and BAC. According to the findings of bacterial composition and interactions, the dominant bacterial phyla were Proteobacteria (41% in RSF and 56% in BAC) followed by Planctomycetes and Acidobacteria in RSF and BAC systems, which might affect the AOC biodegradation efficiency. Results would be useful in developing AOC treatment and management processes in water treatment plants.

Amine-Containing Membranes with Functionalized Multi-Walled Carbon Nanotubes for CO2/H2 Separation.

Amine-containing mixed-matrix membranes incorporated with amino-functionalized multi-walled carbon nanotubes (AF-MWNTs) were synthesized for CO2/H2 separation based on the facilitated transport mechanism. AF-MWNTs were chosen primarily as the mechanical reinforcing filler to enhance the membrane stability. At 107 °C and 0.2-MPa feed pressure, the membrane incorporated with 10 wt.% AF-MWNTs showed a CO2 permeability of 3196 Barrers and a CO2/H2 selectivity of 205. At the higher feed pressure of 1.5 MPa, owing to the carrier saturation phenomenon, the same membrane exhibited reduced transport performance with a CO2 permeability of 776 Barrers and a CO2/H2 selectivity of 31. These separation performances at both the low and high feed pressures were well above the theoretical upper bound. Furthermore, the incorporation of 10 wt.% AF-MWNTs led to a significant improvement on membrane stability. The transport performance and selective layer thickness of this membrane maintained for 100 h, which suggested that the incorporation of AF-MWNTs improved the resistance to membrane compaction upon a high feed pressure. Therefore, this work is considered as one of the crucial steps to enable the application of facilitated transport membranes to high-pressure gas processing such as syngas purification.

Recent Progress in the Engineering of Polymeric Membranes for CO2 Capture from Flue Gas.

CO2 capture from coal- or natural gas-derived flue gas has been widely considered as the next opportunity for the large-scale deployment of gas separation membranes. Despite the tremendous progress made in the synthesis of polymeric membranes with high CO2/N2 separation performance, only a few membrane technologies were advanced to the bench-scale study or above from a highly idealized laboratory setting. Therefore, the recent progress in polymeric membranes is reviewed in the perspectives of capture system energetics, process synthesis, membrane scale-up, modular fabrication, and field tests. These engineering considerations can provide a holistic approach to better guide membrane research and accelerate the commercialization of gas separation membranes for post-combustion carbon capture.

Bioinspired Metal-Organic Framework for Trace CO2 Capture.

A Zn benzotriazolate metal-organic framework (MOF), [Zn(ZnO2CCH3)4(bibta)3] (1, bibta2- = 5,5'-bibenzotriazolate), has been subjected to a mild CH3CO2-/HCO3- ligand exchange procedure followed by thermal activation to generate nucleophilic Zn-OH groups that resemble the active site of α-carbonic anhydrase. The postsynthetically modified MOF, [Zn(ZnOH)4(bibta)3] (2*), exhibits excellent performance for trace CO2 capture and can be regenerated at mild temperatures. IR spectroscopic data and density functional theory (DFT) calculations reveal that intercluster hydrogen bonding interactions augment a Zn-OH/Zn-O2COH fixation mechanism.

Combined aspiration thrombectomy and continuous intrasinus thrombolysis for cerebral venous sinus thrombosis: technical note and case series.

Cerebral venous sinus thrombosis is an uncommon cause of stroke with high morbidity and mortality rates from venous infarction, intracranial hemorrhage, and extensive cerebral edema. Endovascular treatment with various devices has been proposed as a salvage treatment when standard medical treatment with systemic anticoagulation is ineffective, especially in long segment dural sinus thrombosis. We describe our technique of transvenous endovascular aspiration thrombectomy with large bore thrombectomy catheters, followed by placement of microcatheter for local thrombolytic infusion at the site of thrombosis. We report a retrospective study of angiographic and clinical outcome of six consecutive patients treated with this approach. Endovascular aspiration thrombectomy with large bore catheters followed by continuous local thrombolytic infusion appeared to be a safe and effective salvage treatment for selected patients with cerebral dural venous sinus thrombosis refractory to medical treatment.

Heteromeric TRPV4/TRPC1 channels mediate calcium-sensing receptor-induced nitric oxide production and vasorelaxation in rabbit mesenteric arteries.

Stimulation of calcium-sensing receptors (CaSR) by increasing the external calcium concentration (Ca2+]o) induces endothelium-dependent vasorelaxation through nitric oxide (NO) production and activation of intermediate Ca2+-activated K+ currents (IKCa) channels in rabbit mesenteric arteries. The present study investigates the potential role of heteromeric TRPV4-TRPC1 channels in mediating these CaSR-induced vascular responses. Immunocytochemical and proximity ligation assays showed that TRPV4 and TRPC1 proteins were expressed and co-localised at the plasma membrane of freshly isolated endothelial cells (ECs). In wire myography studies, increasing [Ca2+]o between 1 and 6mM induced concentration-dependent relaxations of methoxamine (MO)-induced pre-contracted tone, which were inhibited by the TRPV4 antagonists RN1734 and HC067047, and the externally-acting TRPC1 blocking antibody T1E3. In addition, CaSR-evoked NO production in ECs measured using the fluorescent NO indicator DAF-FM was reduced by RN1734 and T1E3. In contrast, [Ca2+]o-evoked perforated-patch IKCa currents in ECs were unaffected by RN1734 and T1E3. The TRPV4 agonist GSK1016790A (GSK) induced endothelium-dependent relaxation of MO-evoked pre-contracted tone and increased NO production, which were inhibited by the NO synthase inhibitor L-NAME, RN1734 and T1E3. GSK activated 6pS cation channel activity in cell-attached patches from ECs which was blocked by RN1734 and T1E3. These findings indicate that heteromeric TRPV4-TRPC1 channels mediate CaSR-induced vasorelaxation through NO production but not IKCa channel activation in rabbit mesenteric arteries. This further implicates CaSR-induced pathways and heteromeric TRPV4-TRPC1 channels in regulating vascular tone.

Big conductance calcium-activated potassium channel openers control spasticity without sedation.

BACKGROUND AND PURPOSE: Our initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis (MS), whilst avoiding the sedative side effects associated with cannabis. VSN16R was synthesized as an anandamide (endocannabinoid) analogue in an anti-metabolite approach to identify drugs that target spasticity. EXPERIMENTAL APPROACH: Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue-based assays and in vivo animal models, were used to demonstrate the activity, efficacy, pharmacokinetics and mechanism of action of VSN16R. Toxicological and safety studies were performed in animals and humans. KEY RESULTS: VSN16R had nanomolar activity in tissue-based, functional assays and dose-dependently inhibited spasticity in a mouse experimental encephalomyelitis model of MS. This effect occurred with over 1000-fold therapeutic window, without affecting normal muscle tone. Efficacy was achieved at plasma levels that are feasible and safe in humans. VSN16R did not bind to known CB1 /CB2 /GPPR55 cannabinoid-related receptors in receptor-based assays but acted on a vascular cannabinoid target. This was identified as the major neuronal form of the big conductance, calcium-activated potassium (BKCa ) channel. Drug-induced opening of neuronal BKCa channels induced membrane hyperpolarization, limiting excessive neural-excitability and controlling spasticity. CONCLUSIONS AND IMPLICATIONS: We identified the neuronal form of the BKCa channel as the target for VSN16R and demonstrated that its activation alleviates neuronal excitability and spasticity in an experimental model of MS, revealing a novel mechanism to control spasticity. VSN16R is a potential, safe and selective ligand for controlling neural hyper-excitability in spasticity.

Pro-contractile effects of perivascular fat in health and disease.

Perivascular adipose tissue (PVAT) is now recognized as an active player in vascular homeostasis. The expansion of PVAT in obesity and its possible role in vascular dysfunction have attracted much interest. In terms of the regulation of vascular tone and blood pressure, PVAT has been shown to release vasoactive mediators, for instance, angiotensin peptides, reactive oxygen species, chemokines and cytokines. The secretory profile of PVAT is altered by obesity, hypertension and other cardiovascular diseases, leading to an imbalance between its pro-contractile and anti-contractile effects. PVAT adipocytes represent an important source of the mediators, but infiltrating immune cells may become more important under conditions of hypoxia and inflammation. This review describes recent advances in the effects of PVAT on the regulation of vascular tone, highlighting the evidence for a pro-contractile action in health and disease. The role of the endothelium, vascular smooth muscle, immune cells and probably perivascular nerves in PVAT function is also discussed. LINKED ARTICLES: This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.

The calcilytics Calhex-231 and NPS 2143 and the calcimimetic Calindol reduce vascular reactivity via inhibition of voltage-gated Ca2+ channels.

The present study investigates the effect of commonly used negative and positive allosteric modulators of the calcium-sensing receptor (CaSR) on vascular reactivity. In wire myography studies, increasing [Ca2+]o from 1mM to 6mM induced concentration-dependent relaxations of methoxamine-induced pre-contracted rabbit mesenteric arteries, with 6mM [Ca2+]o producing almost complete relaxation. [Ca2+]o-induced relaxations were attenuated in the presence of the calcilytics Calhex-231 and NPS 2143, and abolished by the removal of the endothelium. In addition to their calcilytic effects, Calhex-231 and NPS 2143 also produced concentration-dependent inhibitions of methoxamine- or KCl-induced precontracted tone, which were unaffected by removal of the endothelium and unopposed in the presence of the calcimimetic Calindol. In vessels with depleted Ca2+ stores, contractions mediated by Ca2+ influx via voltage-gated Ca2+ channels (VGCCs) were inhibited by Calhex231. In freshly isolated single rabbit mesenteric artery smooth muscle cells, Calhex-231 and NPS 2143 inhibited whole-cell VGCC currents. Application of Calindol also inhibited methoxamine- and KCl-induced pre-contracted tone, and inhibited whole-cell VGCC currents. In conclusion, in addition to their CaSR-mediated actions in the vasculature, Calhex-231, NPS 2143 and Calindol reduce vascular contractility via direct inhibition of VGCCs.

Stimulation of calcium-sensing receptors induces endothelium-dependent vasorelaxations via nitric oxide production and activation of IKCa channels.

Stimulation of vascular calcium-sensing receptors (CaSRs) is reported to induce both constrictions and relaxations. However, cellular mechanisms involved in these responses remain unclear. The present study investigates the effect of stimulating CaSRs on vascular contractility and focuses on the role of the endothelium, nitric oxide (NO) and K(+) channels in these responses. In wire myography studies, increasing [Ca(2+)]o from 1mM to 6mM induced concentration-dependent relaxations of methoxamine pre-contracted rabbit mesenteric arteries. [Ca(2+)]o-induced relaxations were dependent on a functional endothelium, and were inhibited by the negative allosteric CaSR modulator Calhex-231. [Ca(2+)]o-induced relaxations were reduced by inhibitors of endothelial NO synthase, guanylate cyclase, and protein kinase G. CaSR activation also induced NO production in freshly isolated endothelial cells (ECs) in experiments using the fluorescent NO indicator DAF-FM. Pre-treatment with inhibitors of large (BKCa) and intermediate (IKCa) Ca(2+)-activated K(+) channels (iberiotoxin and charybdotoxin), and Kv7 channels (linopirdine) also reduced [Ca(2+)]o-induced vasorelaxations. Increasing [Ca(2+)]o also activated IKCa currents in perforated-patch recordings of isolated mesenteric artery ECs. These findings indicate that stimulation of CaSRs induces endothelium-dependent vasorelaxations which are mediated by two separate pathways involving production of NO and activation of IKCa channels. NO stimulates PKG leading to BKCa activation in vascular smooth muscle cells, whereas IKCa activity contributes to endothelium-derived hyperpolarisations.

Role of endothelial TRPV4 channels in vascular actions of the endocannabinoid, 2-arachidonoylglycerol.

BACKGROUND AND PURPOSE: Metabolites of the endocannabinoid, 2-arachidonoylglycerol (2-AG) have been postulated to act as endogenous activators of TRPV4, a Ca(2+) -permeable cation channel that plays a critical role in endothelium-dependent relaxation. However, it is unclear if TRPV4 contributes to the vascular actions of 2-AG. EXPERIMENTAL APPROACH: Isometric tension recording of rat small mesenteric arteries and aortae were used to assess the effect of 2-AG and the synthetic TRPV4 activator, GSK1016790A (GSK) on vascular reactivity. Changes in intracellular Ca(2+) concentration and single-channel currents were measured in TRPV4-expressing human coronary endothelial cells. KEY RESULTS: In mesenteric arteries, endothelium-dependent relaxation to both 2-AG and GSK was attenuated by structurally distinct TRPV4 antagonists, HC067047, RN1734 and ruthenium red. The responses were inhibited by KCa inhibitors (apamin + charybdotoxin) and a gap junction inhibitor (18α-glycyrrhetinic acid). In contrast to GSK, 2-AG elicited considerable relaxation independently of the endothelium or TRPV4. Inhibition of 2-AG metabolism via monoacylglycerol lipase and COX (by MAFP and indomethacin) caused potentiation, while cytochrome P450 and lipoxygenase inhibitors had no effect on 2-AG relaxation. In coronary endothelial cells, 2-AG (with and without MAFP) induced HC067047-sensitive increases in intracellular Ca(2+) concentration. 2-AG also increased TRPV4 channel opening in inside-out patches. However, in aortae, GSK induced a relaxation sensitive to HC067047 and ruthenium red, whereas 2-AG induced contractions. CONCLUSIONS AND IMPLICATIONS: These data suggest that 2-AG can directly activate endothelial TRPV4, which partly contributes to the relaxant response to 2-AG. However, the functional role of TRPV4 is highly dependent on the vascular region.

Bendable Zeolite Membranes: Synthesis and Improved Gas Separation Performance.

Separation and sequestration of CO2 emitted from fossil energy fueled electric generating units and industrial facilities will help in reducing anthropogenic CO2, thereby mitigating its adverse climate change effects. Membrane-based gas separation has the potential to meet the technical challenges of CO2 separation if high selectivity and permeance with low costs for large-scale manufacture are realized. Inorganic zeolite membranes in principle can have selectivity and permeance considerably higher than polymers. This paper presents a strategy for zeolite growth within the pores of a polymer support, with crystallization time of an hour. With a thin coating of 200-300 nm polydimethylsiloxane (PDMS) on the zeolite-polymer composite, transport data for CO2/N2 separation indicate separation factors of 35-45, with CO2 permeance between 1600 and 2200 GPU (1 GPU = 3.35 × 10(-10) mol/(m(2) s Pa)) using dry synthetic mixtures of CO2 and N2 at 25 °C. The synthesis process results in membranes that are highly reproducible toward transport measurements and exhibit long-term stability (3 days). Most importantly, these membranes because of the zeolite growth within the polymer support, as contrasted to conventional zeolite growth on top of a support, are mechanically flexible.

Fabrication of zeolite/polymer multilayer composite membranes for carbon dioxide capture: Deposition of zeolite particles on polymer supports.

Membranes, due to their smaller footprint and potentially lower energy consumption than the amine process, offer a promising route for post-combustion CO2 capture. Zeolite Y based inorganic selective layers offer a favorable combination of CO2 permeance and CO2/N2 selectivity, membrane properties crucial to the economics. For economic viability on large scale, we propose to use flexible and scalable polymer supports for inorganic selective layers. The work described in this paper developed a detailed protocol for depositing thin zeolite Y seed layers on polymer supports, the first step in the synthesis of a polycrystalline zeolite Y membrane. We also studied the effects of support surface morphology (pore size and surface porosity) on the quality of deposition and identified favorable supports for the deposition. Two different zeolite Y particles with nominal sizes of 200 nm and 40 nm were investigated. To obtain a complete coverage of zeolite particles on the support surface with minimum defects and in a reproducible manner, a vacuum-assisted dip-coating technique was developed. Images obtained using both digital camera and optical microscope showed the presence of color patterns on the deposited surface which suggested that the coverage was complete. Electron microscopy revealed that the particle packing was dense with some drying cracks. Layer thickness with the larger zeolite Y particles was close to 1 µm while that with the smaller particles was reduced to less than 0.5 µm. In order to reduce drying cracks for layers with smaller zeolite Y particles, thickness was reduced by lowering the dispersion concentration. Transport measurement was used as an additional technique to characterize these layers.

Rapid crystallization of faujasitic zeolites: mechanism and application to zeolite membrane growth on polymer supports.

Zeolites are microporous, crystalline aluminosilicates with the framework made up of T-O-T (T = Si, Al) bonds and enclosed cages and channels of molecular dimensions. Influencing and manipulating the nucleation and growth characteristics of zeolites can lead to novel frameworks and morphologies, as well as decreased crystallization time. In this study, we show that manipulating the supersaturation during synthesis of zeolite X/Y (FAU) via dehydration led to extensive nucleation. Controlled addition of water to this nucleated state promotes the transport of nutrients, with a 4-fold increase in the rate of crystal growth, as compared to conventional hydrothermal process. Structural signature of the nucleated state was obtained by electron microscopy, NMR, and Raman spectroscopy. This extensively intermediate nucleated state was isolated and used as the starting material for zeolite membrane synthesis on porous polymer supports, with membrane formation occurring within an hour. With this time frame for growth, it becomes practical to fabricate zeolite/polymer membranes using roll-to-roll technology, thus making possible new commercial applications.

Berberine induces apoptosis via the mitochondrial pathway in liver cancer cells.

Current chemotherapeutic strategies for liver cancer have limitations. Thus, the demand for complementary medicine is warranted. We evaluated the antitumor potential of berberine, a naturally bioactive phytochemical from Coptis chinensis Franch against Huh7 cancer cells and WRL68 liver cells. The antitumor activity of berberine was evaluated by flow cytometry. The caspase-dependent pathway was assessed using western blot analysis. Results showed that berberine induced the apoptosis of liver cancer cells through procaspase-9, and its effector caspases, procaspase-3 and procaspase-7. Flow cytometry revealed that berberine caused cell cycle arrest at the M/G1 phase. The results of reverse transcription-polymerase chain reaction showed that berberine increased the expression of Bax, which resulted in the activation of the caspase cascade. The present findings demonstrated that berberine induces the apoptosis of Huh7 cells via the mitochondrial pathway.

Effective contractile response to voltage-gated Na+ channels revealed by a channel activator.

This study investigated the molecular identity and impact of enhancing voltage-gated Na(+) (Na(V)) channels in the control of vascular tone. In rat isolated mesenteric and femoral arteries mounted for isometric tension recording, the vascular actions of the Na(V) channel activator veratridine were examined. Na(V) channel expression was probed by molecular techniques and immunocytochemistry. In mesenteric arteries, veratridine induced potent contractions (pEC(50) = 5.19 ± 0.20, E(max) = 12.0 ± 2.7 mN), which were inhibited by 1 µM TTX (a blocker of all Na(V) channel isoforms, except Na(V)1.5, Na(V)1.8, and Na(V)1.9), but not by selective blockers of Na(V)1.7 (ProTx-II, 10 nM) or Na(V)1.8 (A-80347, 1 µM) channels. The responses were insensitive to endothelium removal but were partly (~60%) reduced by chemical destruction of sympathetic nerves by 6-hydroxydopamine (2 mM) or antagonism at the α1-adrenoceptor by prazosin (1 µM). KB-R7943, a blocker of the reverse mode of the Na(+)/Ca(2+) exchanger (3 µM), inhibited veratridine contractions in the absence or presence of prazosin. T16A(inh)-A01, a Ca(2+)-activated Cl(-) channel blocker (10 µM), also inhibited the prazosin-resistant contraction to veratridine. Na(V) channel immunoreactivity was detected in freshly isolated mesenteric myocytes, with apparent colocalization with the Na(+)/Ca(2+) exchanger. Veratridine induced similar contractile effects in the femoral artery, and mRNA transcripts for Na(V)1.2 and Na(V)1.3 channels were evident in both vessel types. We conclude that, in addition to sympathetic nerves, NaV channels are expressed in vascular myocytes, where they are functionally coupled to the reverse mode of Na(+)/Ca(2+) exchanger and subsequent activation of Ca(2+)-activated Cl(-) channels, causing contraction. The TTX-sensitive Na(V)1.2 and Na(V)1.3 channels are likely involved in vascular control.

Modulation by 17ß-estradiol of anandamide vasorelaxation in normotensive and hypertensive rats: a role for TRPV1 but not fatty acid amide hydrolase.

Recent studies suggest that endocannabinoid signaling is modulated by 17ß-estradiol (17Eß) however it is unclear if this applies to the cardiovascular actions of anandamide, a major endocannabinoid. This study examined the in vitro effects of 17Eß on vasorelaxation to anandamide in myograph-mounted small mesenteric arteries obtained from Wistar rats and Spontaneously Hypertensive Rats (SHRs) of both sexes. Treatment with 1µM 17Eß but not its enantiomer 17Eα significantly enhanced relaxation to anandamide in male Wistar rats. This effect was independent of a functional endothelium but was blocked by the Transient Receptor Potential Vanilloid type 1 (TRPV1) receptor antagonist SB366791 (2µM) or prolonged treatment with the TRPV1 agonist capsaicin (10µM). A TRPV1-dependent potentiation by 17Eß was also observed in male SHRs, but not in female Wistar rats or female SHRs. Whilst inhibition of anandamide hydrolysis by 1µM URB597 (an inhibitor of fatty acid amide hydrolase; FAAH) similarly augmented anandamide relaxation in male, but not female, Wistar rats and SHRs, URB597 did not affect the 17Eß-induced potentiation. Female SHRs displayed a larger maximal relaxation to anandamide; however sex difference was not found in Wistar rats. We conclude that pharmacological levels of 17Eß potentiate mesenteric relaxation to anandamide through mechanisms dependent on TRPV1 receptors but not FAAH-mediated hydrolysis in male Wistar rats and male SHRs. Sexual dimorphism was observed in the modulatory effects of 17Eß and URB597, which does not necessarily lead to a greater anandamide response in female rats.

Serum contents of endocannabinoids are correlated with blood pressure in depressed women.

BACKGROUND: Depression is known to be a risk factor for cardiovascular diseases but the underlying mechanisms remain unclear. Since recent preclinical evidence suggests that endogenous agonists of cannabinoid receptors (endocannabinoids) are involved in both cardiovascular function and depression, we asked whether endocannabinoids correlated with either in humans. RESULTS: Resting blood pressure and serum content of endocannabinoids in ambulatory, medication-free, female volunteers with depression (n = 28) and their age- and ethnicity-matched controls (n = 27) were measured. In females with depression, both diastolic and mean arterial blood pressures were positively correlated with serum contents of the endocannabinoids, N-arachidonylethanolamine (anandamide) and 2-arachidonoylglycerol. There was no correlation between blood pressure and endocannabinoids in control subjects. Furthermore, depressed women had significantly higher systolic blood pressure than control subjects. A larger body mass index was also found in depressed women, however, it was not significantly correlated with serum endocannabinoid contents. CONCLUSIONS: This preliminary study raises the possibility that endocannabinoids play a role in blood pressure regulation in depressives with higher blood pressure, and suggests an interrelationship among endocannabinoids, depression and cardiovascular risk factors in women.

BAG3-related myofibrillar myopathy in a Chinese family.

In contrast to the usual slow disease progression in myofibrillar myopathies, patients with Bag3opathy often have a rapidly progressive and more severe phenotype with a worse prognosis. We describe a Chinese patient, born to non-consanguineous parents, who first presented at age 6 with clumsy walking and difficult climbing staircase. With a history of restrictive lung disease previously diagnosed as asthma, she progressed rapidly with proximal myopathy, rigid spine and bilateral tightening of the Achilles tendons requiring surgical elongation. Hypertrophic cardiomyopathy with restrictive physiology was shown by echocardiogram. Moreover, prolonged QT interval was also noted in the patient. Family history was unremarkable yet her father was incidentally found to have prolonged QT interval. Mutation analysis with genomic DNA of the proband showed heterozygous de novo known mutation c.626C>T (p.Pro209Leu) and a germline variation c.772C>T (p.Arg258Trp) in BAG3. Her father was found to be a carrier of c.772C>T. Muscle biopsy findings were suggestive of myofibrillar myopathy on light microscopy and ultrastructural studies. To our knowledge, this is the first Chinese case of Bag3opathy so far reported.