Abdominal compartment syndrome during intraoperative hyperthermic intraperitoneal chemotherapy following debulking surgery for colorectal cancer: A case report.

INTRODUCTION: Colorectal cancer leads to peritoneal metastasis in 8-15 % of cases and necessitates treatments, such as hyperthermic intraperitoneal chemotherapy (HIPEC). However, HIPEC may result in perioperative complications, some often overlooked, such as abdominal compartment syndrome. CASE PRESENTATION: A 52-year-old female with colorectal cancer and peritoneal metastasis underwent debulking surgery followed by HIPEC. During HIPEC, a sudden increase in airway pressure and severe hypotension were noted. Pneumothorax with abdominal compartment syndrome (ACS) was suspected and HIPEC was terminated. Despite intravenous fluids and vasopressors, she experienced circulatory and respiratory collapse. Laparotomy sutures were promptly removed, which effectively alleviated the intra-abdominal hypertension and immediately restored the vital signs. An inadequately repaired diaphragm defect was identified and repaired. A chest tube was inserted for pleural effusion. DISCUSSION: ACS is characterized by an increase in abdominal cavity pressure above 20 mmHg, leading to end-organ damage. It can mimic physiological effects of HIPEC and result in adverse outcomes. Early detection of ACS is essential, especially when complicated by pneumothorax from diaphragmatic tumor dissection. The closed technique for HIPEC, while efficient, can increase the risk of ACS and requires careful management. CONCLUSIONS: This case underscores the complexity of HIPEC and the importance of promptly identifying and managing ACS during the procedure. Monitoring intra-abdominal pressure during HIPEC is essential. Thoroughly check for iatrogenic injuries, including the diaphragm, is crucial before starting before HIPEC.

Albiflorin Decreases Glutamate Release from Rat Cerebral Cortex Nerve Terminals (Synaptosomes) through Depressing P/Q-Type Calcium Channels and Protein Kinase A Activity.

The purpose of this study was to investigate whether and how albiflorin, a natural monoterpene glycoside, affects the release of glutamate, one of the most important neurotransmitters involved in neurotoxicity, from cerebrocortical nerve terminals (synaptosomes) in rats. The results showed that albiflorin reduced 4-aminopyridine (4-AP)-elicited glutamate release from synaptosomes, which was abrogated in the absence of extracellular Ca2+ or in the presence of the vesicular glutamate transporter inhibitor or a P/Q-type Ca2+ channel inhibitor, indicating a mechanism of action involving Ca2+-dependent depression of vesicular exocytotic glutamate release. Albiflorin failed to alter the increase in the fluorescence intensity of 3,3-diethylthiacarbocyanine iodide (DiSC3(5)), a membrane-potential-sensitive dye. In addition, the suppression of protein kinase A (PKA) abolished the effect of albiflorin on glutamate release. Albiflorin also reduced the phosphorylation of PKA and synaptosomal-associated protein of 25 kDa (SNAP-25) and synapsin I at PKA-specific residues, which correlated with decreased available synaptic vesicles. The results of transmission electron microscopy (TEM) also observed that albiflorin reduces the release competence of synaptic vesicles evoked by 4-AP in synaptosomes. In conclusion, by studying synaptosomally released glutamate, we suggested that albiflorin reduces vesicular exocytotic glutamate release by decreasing extracellular Ca2+ entry via P/Q-type Ca2+ channels and reducing PKA-mediated synapsin I and SNAP-25 phosphorylation.

Effectiveness of Exercise on Fatigue for Patients With Heart Failure: A Systematic Review and Meta-Analysis.

Exercise is the standard treatment for fatigue in heart failure (HF) patients. However, no study has investigated the effect of exercise on improving fatigue and HR-QoL in HF patients. Our study adhered to the Cochrane Handbook for Systematic Reviews of Interventions and followed the PRISMA statement. The date of the last search was October 31, 2021. We included randomized controlled trials (RCTs) using exercise to improve fatigue and HR-QoL. The combined exercise training studies showed improvement in fatigue (SMD = -.51, 95% CI = -.89 to -.12, p = .001, I2 = 48%). The IMT studies showed significantly improved fatigue (MD = -11.36, 95%CI = -15.30 to -7.41, p < .00001, I2 = 54%). However, three studies, with moderate heterogeneity (p = .10, I2 = 56%), showed non-significant changes in HR-QoL (SMD = -0.04, 95% CI = -.45 to .37, p = .83).

Description of Aliirhizobium terrae sp. nov., A Plant Growth-Promoting Bacterium Isolated from a Maize-Rice Rotation Agriculture Field.

A polyphasic taxonomic approach was used to characterize a novel bacterium, designated strain CC-CFT758T, isolated from a maize-rice rotation agriculture field in Taiwan. The cells are aerobic, Gram-stain-negative, rod-shaped, positive for catalase and oxidase, and grow at 20-30 °C (optimal 30 â„ƒ), at pH 6.0-8.0 (optimal 8.0), and with 0-4% (w/v) NaCl (optimum, 2-3%). Phylogenetic analysis based on 16S rRNA gene sequencing, the strain CC-CFT758T belongs to the genus "Aliirhizobium" of the family Rhizobiaceae. The closest known relatives of this strain are "Aliirhizobium wenxiniae" 166T (with 98.7% similarity), "Aliirhizobium cellulosilyticum" SEMIA 448T (with 97.9% similarity), and "Aliirhizobium smilacinae" PTYR-5T (with 97.0% similarity). The genome size was 5.9 Mbp, with a G + C content of 60.6%. Values of digital DNA-DNA hybridization between the strain and closely related species were 29.5% for "Ali. cellulosilyticum", and 23.9% for "Ali. wenxiniae" and "Ali. smilacinae". Strain CC-CFT758T exhibited the highest orthologous average nucleotide identity (OrthoANI) values with members of the genus "Aliirhizobium", ranging from 80.4 to 81.6% (n = 3). Chemotaxonomical analysis indicated that strain CC-CFT758T contained C16:0, C16:0 3OH, C19:0 cyclo ω8c, C14:0 3OH/iso-C16:1 I, and C18:2 ω6,9c/ante C18:0 as dominant fatty acids, and the major polyamines were putrescine and spermidine. The polar lipids comprised diphosphatidylglycerol, phosphatidylcholin, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, seven unidentified aminolipids, three unidentified phospholipids, and two unidentified polar lipids. Strain CC-CFT758T exhibited distinct phylogenetic, phenotypic, and chemotaxonomic characteristics, as well as unique results in comparative analysis of 16S rRNA gene sequence, OrthoANI, AAI, dDDH, and phylogenomic placement. Therefore, this strain represents a new species of the genus "Aliirhizobium", for which the name Aliirhizobium terrae sp. nov. is proposed, with the type strain is CC-CFT758T (= BCRC 81364T = JCM 35482T).

Inequality in Older Volunteering: Association Between Volunteer Competency and Demographic Profiles.

The present survey research investigated older people's volunteering competency relating to social inequality by exploring the latent ability profile and demographic correlates of 1,000 older volunteers in 73 community care centersin southern Taiwan. Older volunteers were classified into advanced (n = 509), basic (n = 214), and novice (n = 277) groups. Demographics examined included: individualistic characteristics (religious beliefs), resources (education; number of chronic diseases), andsocial factors (serving area and spoken language, volunteering duration, marital status, and gender). Apparent inequality issues were revealed. The advanced group was better educated, Mandarin-speaking, and in urban areas. while the novice group featured the opposite (lower education Taiwanese-speaking suburban areas).

Gypenoside XVII Reduces Synaptic Glutamate Release and Protects against Excitotoxic Injury in Rats.

Excitotoxicity is a common pathological process in neurological diseases caused by excess glutamate. The purpose of this study was to evaluate the effect of gypenoside XVII (GP-17), a gypenoside monomer, on the glutamatergic system. In vitro, in rat cortical nerve terminals (synaptosomes), GP-17 dose-dependently decreased glutamate release with an IC50 value of 16 µM. The removal of extracellular Ca2+ or blockade of N-and P/Q-type Ca2+ channels and protein kinase A (PKA) abolished the inhibitory effect of GP-17 on glutamate release from cortical synaptosomes. GP-17 also significantly reduced the phosphorylation of PKA, SNAP-25, and synapsin I in cortical synaptosomes. In an in vivo rat model of glutamate excitotoxicity induced by kainic acid (KA), GP-17 pretreatment significantly prevented seizures and rescued neuronal cell injury and glutamate elevation in the cortex. GP-17 pretreatment decreased the expression levels of sodium-coupled neutral amino acid transporter 1, glutamate synthesis enzyme glutaminase and vesicular glutamate transporter 1 but increased the expression level of glutamate metabolism enzyme glutamate dehydrogenase in the cortex of KA-treated rats. In addition, the KA-induced alterations in the N-methyl-D-aspartate receptor subunits GluN2A and GluN2B in the cortex were prevented by GP-17 pretreatment. GP-17 also prevented the KA-induced decrease in cerebral blood flow and arginase II expression. These results suggest that (i) GP-17, through the suppression of N- and P/Q-type Ca2+ channels and consequent PKA-mediated SNAP-25 and synapsin I phosphorylation, reduces glutamate exocytosis from cortical synaptosomes; and (ii) GP-17 has a neuroprotective effect on KA-induced glutamate excitotoxicity in rats through regulating synaptic glutamate release and cerebral blood flow.

Toward Characterizing Environmental Sources of Non-tuberculous Mycobacteria (NTM) at the Species Level: A Tutorial Review of NTM Phylogeny and Phylogenetic Classification.

Nontuberculous mycobacteria (NTM) are any mycobacteria that do not cause tuberculosis or leprosy. While the majority of NTM are harmless and some of them are considered probiotic, a growing number of people are being diagnosed with NTM infections. Therefore, their detection in the environment is of interest to clinicians, environmental microbiologists, and water quality researchers alike. This review provides a tutorial on the foundational approaches for taxonomic classifications, with a focus on the phylogenetic relationships among NTM revealed by the 16S rRNA gene, rpoB gene, and hsp65 gene, and by genome-based approaches. Recent updates on the Mycobacterium genus taxonomy are also provided. A synthesis on the habitats of 189 mycobacterial species in a genome-based taxonomy framework was performed, with attention paid to environmental sources (e.g., drinking water, aquatic environments, and soil). The 16S rRNA gene-based classification accuracy for various regions was evaluated (V3, V3-V4, V3-V5, V4, V4-V5, and V1-V9), revealing overall excellent genus-level classification (up to 100% accuracy) yet only modest performance (up to 63.5% accuracy) at the species level. Future research quantifying NTM species in water systems, determining the effects of water treatment and plumbing conditions on their variations, developing high throughput species-level characterization tools for use in the environment, and incorporating the characterization of functions in a phylogenetic framework will likely fill critical knowledge gaps. We believe this tutorial will be useful for researchers new to the field of molecular or genome-based taxonomic profiling of environmental microbiomes. Experts may also find this review useful in terms of the selected key findings of the past 30 years, recent updates on phylogenomic analyses, as well as a synthesis of the ecology of NTM in a phylogenetic framework.

Development and testing of a four-item version of the physical resilience instrument for older adults (PRIFOR-4).

The 16-item Physical Resilience Instrument for Older Adults (PRIFOR) has good clinimetric properties; however, a shortened PRIFOR would greatly enhance physical resilience measurements in clinical settings. The current analysis aimed to reduce the number of PRIFOR while maintaining its clinimetric properties, emphasizing on its factor structure and convergent validity. A longitudinal study was conducted among 863 patients aged 65 years or older. Four PRIFOR items with high factor loadings were selected to generate the short version of PRIFOR (PRIFOR-4). The PRIFOR-4 was found to have a unidimensional structure (comparative fit index = 0.999; Tucker-Lewis index = 0.998 in the confirmatory factor analysis results) with good convergent validity with various external measures (absolute r = 0.109-0.597; p-values<0.01). Because the PRIFOR-4 contains only four items, the completion time for the respondents reduced three fourths from the original PRIFOR, which may have a marked reduction in the response burden. The PRIFOR-4 is thus an easy-to-use measurement that saves time for healthcare professionals in clinical practice.

Trends in exposure to drugs and prohibited substances among sports: A nationwide analysis of 2008-2022 inquiry records.

To prevent athletes from unintentional doping, the anti-doping authorities in Taiwan have launched several sports-prohibited substances inquiry services since 2008. This study aimed to enhance the prevention of sports-prohibited substance misuse by analyzing data collected from major nationwide service systems, enabling the identification of trends in athletes' exposure to drugs and prohibited substances. The study collected over 30,000 data points from three major national anti-doping inquiry systems, spanning from 2008 to 2022. The information of the users consulted products, prohibited substances, and sports disciplines in the data were calculated and categorized. The usage of inquiry systems has shown an increasing trend from 2008 to 2022. Athletes comprised the majority of users (> 40%), significantly outnumbering other user groups (all below 20%). Among the inquiries, Western medicine accounted for the highest percentage (up to 79.6%), and it also contained the majority of the prohibited substances. Interestingly, traditional Chinese medicines had a higher chance (35.9%) of containing prohibited substances, as indicated by the mobile application. The prohibited substances mainly belonged to class S6 stimulants and S9 glucocorticoids. Among the daily medicinal products and nutritional supplements encountered by sports personnel, approximately 30% of them were found to contain prohibited substances. Future educational efforts should focus on raising awareness about traditional Chinese medicines and drugs for the common cold, ADHD, and pain relief, as well as their regulation, to prevent the misuse of prohibited substances.

Phillygenin Suppresses Glutamate Exocytosis in Rat Cerebrocortical Nerve Terminals (Synaptosomes) through the Inhibition of Cav2.2 Calcium Channels.

Glutamate is a major excitatory neurotransmitter that mediates neuronal damage in acute and chronic brain disorders. The effect and mechanism of phillygenin, a natural compound with neuroprotective potential, on glutamate release in isolated nerve terminals (synaptosomes) prepared from the rat cerebral cortex were examined. In this study, 4-aminopyridine (4-AP), a potassium channel blocker, was utilized to induce the release of glutamate, which was subsequently quantified via a fluorometric assay. Our findings revealed that phillygenin reduced 4-AP-induced glutamate release, and this inhibitory effect was reversed by removing extracellular Ca2+ or inhibiting vesicular transport with bafilomycin A1. However, exposure to the glutamate transporter inhibitor dl-threo-beta-benzyl-oxyaspartate (dl-TOBA) did not influence the inhibitory effect. Moreover, phillygenin did not change the synaptosomal membrane potential but lowered the 4-AP-triggered increase in intrasynaptosomal Ca2+ concentration ([Ca2+]i). Antagonizing Cav2.2 (N-type) calcium channels blocked the inhibition of glutamate release by phillygenin, whereas pretreatment with the mitochondrial Na+/Ca2+ exchanger inhibitor, CGP37157 or the ryanodine receptor inhibitor, dantrolene, both of which block intracellular Ca2+ release, had no effect. The effect of phillygenin on glutamate release triggered by 4-AP was completely abolished when MAPK/ERK inhibitors were applied. Furthermore, phillygenin attenuated the phosphorylation of ERK1/2 and its major presynaptic target, synapsin I, a protein associated with synaptic vesicles. These data collectively suggest that phillygenin mediates the inhibition of evoked glutamate release from synaptosomes primarily by reducing the influx of Ca2+ through Cav2.2 calcium channels, thereby subsequently suppressing the MAPK/ERK/synapsin I signaling cascade.

Nitric oxide and tumor necrosis factor-⍺ levels are negatively correlated in endotoxin tolerance recovery in vitro.

Endotoxin tolerance (ET) is the hyporesponsiveness to lipopolysaccharide (LPS) after prior exposure. It is characterized by the downregulation of pro-inflammatory cytokine levels. Although ET protects against inflammation, its abolishment or recovery is critical for immunity. Nitric oxide (NO) plays various roles in the development of ET; however, its specific role in ET recovery remains unknown. To induce ET, RAW264.7 cells (a murine macrophage cell line) were pre-exposed to LPS (LPS1, 100 ng/mL for 24 h) and subsequently re-stimulated with LPS (LPS2, 100 ng/mL for 24 h). Expression of cytokines, NO, nitrite and inducible NO synthase (iNOS) were measured after 0, 12, 24, and 36 h of resting after LPS1 treatment with or without the iNOS-specific inhibitor, 1400W. LPS2-induced tumor necrosis factor-⍺ (TNF-⍺) and interleukin-6 (IL-6) were downregulated after LPS1 treatment, confirming the development of ET. Notably, TNF-⍺ and IL-6 levels spontaneously rebounded after 12-24 h of resting following LPS1 treatment. In contrast, levles of NO, nitrite and iNOS increased during ET development and decreased during ET recovery. Moreover, 1400W inhibited ET development and blocked the early production of NO (<12 h) during ET recovery. Our findings suggest a negative correlation between iNOS-induced NO and cytokine levels in the abolishment of ET.

Establishing psychometric properties of the older volunteer competency scale in the community.

AIM(S): To investigate the factorial structure, test-retest reliability, and internal consistency of the Older Volunteer Competency Scale and establish its psychometric properties. DESIGN: Cross-sectional survey. METHODS: A total of 1,000 older volunteers were recruited through random sampling and asked to complete the Older Volunteer Competency Scale. Subsequently, 100 participants were selected to participate in a second test to determine the scale's test-retest reliability. Factorial structure was assessed through exploratory factor analysis and confirmatory factor analysis, and internal consistency was assessed using Cronbach's α. RESULTS: Favorable exploratory and confirmatory factor analysis results were obtained. In addition, the three dimensions of the Older Volunteer Competency Scale, namely service awareness, service skills, and interpersonal interaction, had high internal consistency and test-retest reliability. CONCLUSION: The Older Volunteer Competency Scale is an effective and reliable research instrument for evaluating competency and needs among older volunteers.

Spatial Analysis of Home and Community-Based Services and Number of Deaths Among Older Adults in Taiwan.

This study examined the geographical distribution of home- and community-based services (HCBS) resources in Taiwan's Long-Term Care 2.0 policy and explored its association with the number of deaths among older adults. The main outcome of the study was determination of the number of deaths among older adults in townships (N = 346) in 2021. The results showed that home-based HCBS had a significant positive association with mortality among older adults; moreover, community-based and complementary services, which are highly clustered within a township and among its neighbors, exert a significant protective effect on mortality among older adults. Stratified analyses showed a significantly lower mortality among older adults using adult foster care and transportation services, but a significantly higher mortality among older adults using home-based professional care and respite care services, after considering the sociodemographic characteristics of older adults, urbanization, and the number of long-term care resources in the spatial analysis.

Biological upgrading of biogas assisted with membrane supplied hydrogen gas in a three-phase upflow reactor.

Biogas upgrading via CO2 conversion to CH4 is an emerging technology for renewable natural gas production and carbon management, but its development is limited by the low H2 gas to liquid phase transfer. Herein, an innovative biogas upgrading system employing a three-phase design was studied for CO2 conversion with H2 supply via gas-permeable membrane. The system produced biogas consisted of 74.1 ± 7.1 % CH4 and 25.9 ± 7.1 % CO2 with intermittent injection of H2. When H2 supply was continuous, the CH4 content increased to 91.6 ± 2.2 % at a H2:CO2 ratio of 4.4. Although a higher ratio of 5.5 could result in a higher CH4 percentage of 95.2 ± 2.5 %, biogas production rate started to decrease. The removal efficiency of organic contents remained above 90 % throughout the experiment. Microbial community analysis corroborated the findings, showing that hydrogenotrophic Methanobacteriaceae was more prevalent in the biofilm (71.9 %) compared to that in anaerobic digestion (15.8 %) and effluent (14.1 %).

Highly Efficient MAPbI3 -Based Quantum Dots Exhibiting Unusual Nonblinking Single Photon Emission at Room Temperature.

Highly emissive semiconductor nanocrystals, or so-called quantum dots (QDs) possess a variety of applications from displays and biology labeling, to quantum communication and modern security. Though ensembles of QDs have already shown very high photoluminescent quantum yields (PLQYs) and have been widely utilized in current optoelectronic products, QDs that exhibit high absorption cross-section, high emission intensity, and, most important, nonblinking behavior at single-dot level have long been desired and not yet realized at room temperature. In this work, infrared-emissive MAPbI3 -based halide perovskite QDs is demonstrated. These QDs not only show a ≈100% PLQY at the ensemble level but also, surprisingly, at the single-dot level, display an extra-large absorption cross-section up to 1.80 × 10-12 cm2 and non-blinking single photon emission with a high single photon purity of 95.3%, a unique property that is extremely rare among all types of quantum emitters operated at room temperature. An in-depth analysis indicates that neither trion formation nor band-edge carrier trapping is observed in MAPbI3 QDs, resulting in the suppression of intensity blinking and lifetime blinking. Fluence-dependent transient absorption measurements reveal that the coexistence of non-blinking behavior and high single photon purity in these perovskite QDs results from a significant repulsive exciton-exciton interaction, which suppresses the formation of biexciton, and thus greatly reduces photocharging. The robustness of these QDs is confirmed by their excellent stability under continuous 1 h electron irradiation in high-resolution transmission electron microscope inspection. It is believed that these results mark an important milestone in realizing nonblinking single photon emission in semiconductor QDs.

Neopusillimonas aromaticivorans sp. nov. isolated from poultry manure.

A polyphasic taxonomic approach was used to characterize a novel bacterium, designated strain CC-YST667T, isolated from poultry manure sampled in Taiwan. The cells were observed to be aerobic, motile and non-spore-forming rods, displaying positive reactions for oxidase. Optimal growth of CC-YST667T was observed at 25 °C, pH 8.0 and with 1 % (w/v) NaCl. The polar lipid profile consisted of phosphatidylmonomethylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and multiple unidentified polar lipids. The major polyamine was spermidine. The major cellular fatty acids (>5 %) included C16 : 0, C17 : 0cyclo, C19 : 0cyclo ω8c and C14 : 0 3OH/iso-C16 : 1 I. On the basis of the results of analysis of 16S rRNA gene sequences, this isolate showed the closest phylogenetic relationship with 'Neopusillimonas minor' (with 98.2 % similarity) and Paralcaligenes ureilyticus (with 97.3 % similarity) of the family Alcaligenaceae. The draft genome, (3.3 Mb) with a DNA G+C content of 57.2 mol%, harboured various genes involved in the biodegradation of aromatic hydrocarbons. CC-YST667T shared highest orthologous average nucleotide identity (OrthoANI) with the type strains of species of of the genera Neopusillimonas (72.4‒77.9 %, n=2), Pusillimonas (72.8‒73.0 %, n=2) and Pollutimonas (71.7‒73.0 %, n=5). On the basis of its distinct phylogenetic, phenotypic and chemotaxonomic traits together with the results of comparative 16S rRNA gene sequencing, OrthoANI, digital DNA-DNA hybridization (DDH) and the phylogenomic placement, strain CC-YST667T is considered to represent a novel species of the genus Neopusillimonas, for which the name Neopusillimonas aromaticivorans sp. nov. is proposed. The type strain is CC-YST667T (=BCRC 81321T =JCM 34761T).

Validation of 16S rRNA gene sequencing and metagenomics for evaluating microbial immigration in a methanogenic bioreactor.

To quantitatively evaluate the impact of microbial immigration from an upstream community on the microbial assembly of a downstream community, an ecological genomics (ecogenomics)-based mass balance (EGMB) model coupled with 16S rRNA gene sequencing was previously developed. In this study, a mock community was used to further validate the EGMB models and demonstrate the feasibility of using metagenome-based EGMB model to reveal both microbial activity and function. The mock community consisting of Aeromonas, Escherichia, and Pseudomonas was fed into a lab-scale methanogenic bioreactor together with dissolved organic substrate. Using qPCR, 16S rRNA gene, 16S rRNA gene copy number normalization (GCN), and metagenome, results showed highly comparable community profiles in the feed. In the bioreactor, Aeromonas and Pseudomonas exhibited negative growth rates throughout the experiment by all approaches. Escherichia's growth rate was negative by most biomarkers but was slightly positive by 16S rRNA gene. Still, all approaches showed a decreasing trend toward negative in the growth rate of Escherichia as reactor operation time increased. Uncultivated populations of phyla Desulfobacterota, Chloroflexi, Actinobacteriota, and Spirochaetota were observed to increase in abundance, suggesting their contribution in degrading the feed biomass. Based on metabolic reconstruction of metagenomes, these populations possessed functions of hydrolysis, fermentation, fatty acid degradation, or acetate oxidation. Overall results supported the application of both 16S rRNA gene- and metagenome-based EGMB models to measure the growth rate of microbes in the bioreactor, and the latter had advantage in providing insights into the microbial functions of uncultivated populations.

Cynarin, a caffeoylquinic acid derivative in artichoke, inhibits exocytotic glutamate release from rat cortical nerve terminals (synaptosomes).

The purpose of this study was to evaluate the effect of cynarin, a caffeoylquinic acid derivative in artichoke, on glutamate release elicited by 4-aminopyridine (4-AP) in rat cortical nerve terminals (synaptosomes). We observed that cynarin decreased 4-aminopyridine-elicited glutamate release, which was prevented by the removal of external free Ca2+ with ethylene glycol bis (ß-aminoethyl ether)-N,N,N,N-tetraacetic acid (EGTA) or the blockade of P/Q-type calcium channels with ω-agatoxin IVA. Molecular docking also revealed that cynarin formed a hydrogen bond with the P/Q-type Ca2+ channel, indicating a mechanism of action involving Ca2+ influx inhibition. Additionally, the inhibitory effect of cynarin on glutamate release is associated with a change in the available synaptic vesicles, as cynarin decreased 4-AP-elicited FM1-43 release or hypertonic sucrose-evoked glutamate release from synaptosomes. Furthermore, the suppression of protein kinase A (PKA) prevented the effect of cynarin on 4-AP-elicited glutamate release. 4-AP-elicited PKA and synapsin I or synaptosomal-associated protein of 25 kDa (SNAP-25) phosphorylation at PKA-specific residues were also attenuated by cynarin. Our data indicate that cynarin, through the suppression of P/Q-type Ca2+ channels, inhibits PKA activation and attenuates synapsin I and SNAP-25 phosphorylation at PKA-specific residues, thus decreasing synaptic vesicle availability and contributing to glutamate release inhibition in cerebral cortex terminals.

Mangiferin depresses vesicular glutamate release in synaptosomes from the rat cerebral cortex by decreasing synapsin I phosphorylation.

Mangiferin is a glucosyl xanthone that has been shown to be a neuroprotective agent against brain disorders involving excess glutamate. However, the effect of mangiferin on the function of the glutamatergic system has not been investigated. In this study, we used synaptosomes from the rat cerebral cortex to investigate the effect of mangiferin on glutamate release and identify the possible underlying mechanism. We observed that mangiferin produced a concentration-dependent reduction in the release of glutamate elicited by 4-aminopyridine with an IC50 value of 25 µM. Inhibition of glutamate release was blocked by removing extracellular calcium and by treatment with the vacuolar-type H+-ATPase inhibitor bafilomycin A1, which prevents the uptake and storage of glutamate in vesicles. Moreover, we showed that mangiferin decreased the 4-aminopyridine-elicited FM1-43 release and synaptotagmin 1 luminal domain antibody (syt1-L ab) uptake from synaptosomes, which correlated with decreased synaptic vesicle exocytosis. Transmission electron microscopy in synaptosomes also showed that mangiferin attenuated the 4-aminopyridine-elicited decrease in the number of synaptic vesicles. In addition, antagonism of Ca2+/calmodulin-dependent kinase II (CaMKII) and protein kinase A (PKA) counteracted mangiferin's effect on glutamate release. Mangiferin also decreased the phosphorylation of CaMKII, PKA, and synapsin I elicited by 4-aminopyridine treatment. Our data suggest that mangiferin reduces PKA and CaMKII activation and synapsin I phosphorylation, which could decrease synaptic vesicle availability and lead to a subsequent reduction in vesicular glutamate release from synaptosomes.

Plantainoside D Reduces Depolarization-Evoked Glutamate Release from Rat Cerebral Cortical Synaptosomes.

Inhibiting the excessive release of glutamate in the brain is emerging as a promising therapeutic option and is efficient for treating neurodegenerative disorders. The aim of this study is to investigate the effect and mechanism of plantainoside D (PD), a phenylenthanoid glycoside isolated from Plantago asiatica L., on glutamate release in rat cerebral cortical nerve terminals (synaptosomes). We observed that PD inhibited the potassium channel blocker 4-aminopyridine (4-AP)-evoked release of glutamate and elevated concentration of cytosolic Ca2+. Using bafilomycin A1 to block glutamate uptake into synaptic vesicles and EDTA to chelate extracellular Ca2+, the inhibitory effect of PD on 4-AP-evoked glutamate release was prevented. In contrast, the action of PD on the 4-AP-evoked release of glutamate in the presence of dl-TBOA, a potent nontransportable inhibitor of glutamate transporters, was unaffected. PD does not alter the 4-AP-mediated depolarization of the synaptosomal membrane potential, suggesting that the inhibitory effect of PD on glutamate release is associated with voltage-dependent Ca2+ channels (VDCCs) but not the modulation of plasma membrane potential. Pretreatment with the Ca2+ channel blocker (N-type) ω-conotoxin GVIA abolished the inhibitory effect of PD on the evoked glutamate release, as did pretreatment with the protein kinase C inhibitor GF109203x. However, the PD-mediated inhibition of glutamate release was eliminated by applying the mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 or dantrolene, which inhibits Ca2+ release through ryanodine receptor channels. These data suggest that PD mediates the inhibition of evoked glutamate release from synaptosomes primarily by reducing the influx of Ca2+ through N-type Ca2+ channels, subsequently reducing the protein kinase C cascade.