Nicorandil prevents endothelial dysfunction due to antioxidative effects via normalisation of NADPH oxidase and nitric oxide synthase in streptozotocin diabetic rats

<p>Abstract</p> <p>Background</p> <p>Nicorandil, an anti-angina agent, reportedly improves outcomes even in angina patients with diabetes. However, the precise mechanism underlying the beneficial effect of nicorandil on diabetic patients has not been examined. We investigated the protective effect of nicorandil on endothelial function in diabetic rats because endothelial dysfunction is a major risk factor for cardiovascular disease in diabetes.</p> <p>Methods</p> <p>Male Sprague-Dawley rats (6 weeks old) were intraperitoneally injected with streptozotocin (STZ, 40 mg/kg, once a day for 3 days) to induce diabetes. Nicorandil (15 mg/kg/day) and tempol (20 mg/kg/day, superoxide dismutase mimetic) were administered in drinking water for one week, starting 3 weeks after STZ injection. Endothelial function was evaluated by measuring flow-mediated dilation (FMD) in the femoral arteries of anaesthetised rats. Cultured human coronary artery endothelial cells (HCAECs) were treated with high glucose (35.6 mM, 24 h) and reactive oxygen species (ROS) production with or without L-NAME (300 μM), apocynin (100 μM) or nicorandil (100 μM) was measured using fluorescent probes.</p> <p>Results</p> <p>Endothelial function as evaluated by FMD was significantly reduced in diabetic as compared with normal rats (diabetes, 9.7 ± 1.4%; normal, 19.5 ± 1.7%; <it>n </it>= 6-7). There was a 2.4-fold increase in p47^phoxexpression, a subunit of NADPH oxidase, and a 1.8-fold increase in total eNOS expression in diabetic rat femoral arteries. Nicorandil and tempol significantly improved FMD in diabetic rats (nicorandil, 17.7 ± 2.6%; tempol, 13.3 ± 1.4%; <it>n </it>= 6). Nicorandil significantly inhibited the increased expressions of p47^phoxand total eNOS in diabetic rat femoral arteries. Furthermore, nicorandil significantly inhibited the decreased expression of GTP cyclohydrolase I and the decreased dimer/monomer ratio of eNOS. ROS production in HCAECs was increased by high-glucose treatment, which was prevented by L-NAME and nicorandil suggesting that eNOS itself might serve as a superoxide source under high-glucose conditions and that nicorandil might prevent ROS production from eNOS.</p> <p>Conclusions</p> <p>These results suggest that nicorandil improved diabetes-induced endothelial dysfunction through antioxidative effects by inhibiting NADPH oxidase and eNOS uncoupling.</p

The prevalence of foodborne pathogenic bacteria on cutting boards and their ecological correlation with background biota

This study implemented the pyrosequencing technique and real-time quantitative PCR to determine the prevalence of foodborne pathogenic bacteria (FPB) and as well as the ecological correlations of background biota and FPB present on restaurant cutting boards (CBs) collected in Seri Kembangan, Malaysia. The prevalence of FPB in high background biota (HBB) was lower (0.24%) compared to that of low background biota (LBB) (0.54%). In addition, a multiple linear regression analysis indicated that only HBB had a significant ecological correlation with FPB. Furthermore, statistical analysis revealed that the combinations of Clostridiales, Flavobacteriales, and Lactobacillales orders in HBB had significant negative associations with FPB, suggesting that these bacteria may interact to ensure survivability and impair the growth of pathogenic bacteria

Bacterial community shift as potential bioindicator for monitoring the performance of palm oil mill effluent treatment system

The growing demand for palm oil has caused a substantial increase in the generation of palm oil mill effluent (POME). POME has been known to give the adverse environmental impacts including land and aquatic ecosystem contamination and the biodiversity loss if it is not properly treated. In Malaysia, the biological ponding system is commonly being used to treat POME because of the low cost and less maintenance is required. However, the current wastewater treatment system for POME regularly fails to treat the effluent efficiently. To meet the standard discharge limit proposed by the Malaysian Department of the Environment, the POME must be treated effectively before being released into the receiving water bodies, hence monitoring a correct operation of POME treatment system is crucial. However, to date, only few studies have been conducted on the microbial aspects of POME and little is known about microbial diversity involved in the POME treatment system, either in terms of their community structure and function or their response to the environment. Therefore, the study on the microbial community composition of POME treatment system has been carried out which later can be used as potential bioindicator to monitor the performance of the treatment system. Sampling from POME treatment system was done by collecting samples from raw POME, anaerobic tanks, as well as from facultative and algae ponds. The shift of microbial community composition at each stage of POME treatment system has been shown by using PCR-Denaturing Gradient Gel Electrophoresis (DGGE) and Illumina Miseq. As a conclusion, a sensitive and accurate monitoring approach of POME treatment system using bacterial community shift is proposed to ensure a correct operation for POME treatment, hence can be used to complement the current physicochemical assessment method

Bacterial community shift as potential bioindicator to indicate the river water contamination due to palm oil mill effluent final discharge

A thorough outlook on the effect of palm oil mill effluent (POME) final discharge towards the composition and functional status of bacterial community in the receiving river is provided in this study by using high-throughput MiSeq and flow cytometry, respectively. The shift of bacterial community dynamics could be used to determine the potential bacterial indicators to indicate contamination caused by POME. This study showed that the POME final discharge did not only alter the natural physicochemical properties of the river water but also caused the reduction of bacterial diversity in the receiving river. The Chromatiaceae and Alcaligenaceae which were not detected in the upstream but were detected in the downstream part of the river are proposed as the indicator bacteria to indicate the river water contamination caused by POME final discharge. The emergence of the potential indicator bacteria in the downstream part of the river was shown to be carried over by the effluent. Moreover, the functional status of the bacterial community at single-cell level is determined with regards to their abundance, viability and nucleic acid content to monitor the effect of POME final discharge in the affected river. The shift of low nucleic acid (LNA) to high nucleic acid (HNA) bacterial cells in the affected river suggests the transformation of dormant to active cells due to POME final discharge which may serves as potential bioindicator in the screening of anthropogenic effect due to POME final discharge in the river water with originally high LNA proportions. Monitoring the effluent discharge at low trophic level using MiSeq and flow cytometry is considered as an accurate pollution monitoring approach which can be used to complement the conventional POME pollution assessment method

Microbial community changes in different stages of palm oil mill effluent treatment

The growing demand for palm oil has caused a substantial increase in the generation of palm oil mill effluent (POME). POME has been known to give the adverse environmental impacts including land and aquatic ecosystem contamination and the biodiversity loss if it is not properly treated. Currently, the wastewater treatment system for POME regularly fails to treat the effluent efficiently. To meet the standard discharge limit proposed by the Malaysian Department of the Environment, the POME must be treated effectively before being released into the receiving water bodies. In Malaysia, the ponding system is commonly being used to treat POME because of the low cost and less maintenance is required. To date, only few studies have been conducted on the microbial aspects of POME and little is known about microbial diversity involved in POME treatment, either in terms of their community structure and function or their response to the environment. Therefore, the study on the microbial community structure during POME treatment is proposed. Several samples from POME treatment system were collected, including POME samples from anaerobic tanks, as well as from facultative, and algae ponds. The changes of microbial community structure at each stage of POME treatment has been shown by using PCR-Denaturing Gradient Gel Electrophoresis (DGGE) approach. As a conclusion, the microbial community changes during POME treatment is expected to be explored and identified, hence will bring to the microbial community rebound after implementation of zero discharge system in the future

Bacterial community shift for monitoring the co-composting of oil palm empty fruit bunch and palm oil mill effluent anaerobic sludge

A recently developed rapid co-composting of oil palm empty fruit bunch (OPEFB) and palm oil mill effluent (POME) anaerobic sludge is beginning to attract attention from the palm oil industry in managing the disposal of these wastes. However, a deeper understanding of microbial diversity is required for the sustainable practice of the co-compositing process. In this study, an in-depth assessment of bacterial community succession at different stages of the pilot scale co-composting of OPEFB-POME anaerobic sludge was performed using 454-pyrosequencing, which was then correlated with the changes of physicochemical properties including temperature, oxygen level and moisture content. Approximately 58,122 of 16S rRNA gene amplicons with more than 500 operational taxonomy units (OTUs) were obtained. Alpha diversity and principal component analysis (PCoA) indicated that bacterial diversity and distributions were most influenced by the physicochemical properties of the co-composting stages, which showed remarkable shifts of dominant species throughout the process. Species related to Devosia yakushimensis and Desemzia incerta are shown to emerge as dominant bacteria in the thermophilic stage, while Planococcus rifietoensis correlated best with the later stage of co-composting. This study proved the bacterial community shifts in the co-composting stages corresponded with the changes of the physicochemical properties, and may, therefore, be useful in monitoring the progress of co-composting and compost maturity

[11C]Doxepin binding to histamine H1 receptors in living human brain: reproducibility during attentive waking and circadian rhythm

Molecular imaging in neuroscience is a new research field that enables visualization of the impact of molecular events on brain structure and function in humans. While magnetic resonance-based imaging techniques can provide complex information at the level of system, positron emission tomography (PET) enables determination of the distribution and density of receptor and enzyme in the human brain. Previous studies using [11C]raclopride and [11C]FLB457 revealed that the release of neuronal dopamine was increased in human brain by psychostimulants or reward stimuli. Following on from these previous [11C]raclopride studies, we examined whether the levels of neuronal release of histamine might change [11C]doxepin binding to the H1 receptors under the influence of physiological stimuli. The purpose of the present study was to evaluate the test–retest reliability of quantitative measurement of [11C]doxepin binding between morning and afternoon and between resting and attentive waking conditions in healthy human subjects. There was a trend for a decrease in [11C]doxepin binding during attentive calculation tasks compared with that in resting conditions, but the difference (less than 10%) was not significant. Similarly, the binding potential of [11C]doxepin in the cerebral cortex was slightly higher in the morning than that in the afternoon, but it was also insignificant. These data suggest that higher histamine release during wakefulness could not decrease the [11C]doxepin binding in the brain. This study confirmed the reproducibility and reliability of [11C]doxepin in the previous imaging studies to measure the H1 receptor

Analysis of bacterial community structure and function as a tool in assessing the pollution due to palm oil mill effluent

Malaysia is ranked as the second largest producer of palm oil in the world. The major problem in this industry is the production of a highly polluting wastewater known as palm oil mill effluent (POME). POME is considered as the most harmful waste generated from palm oil processing industry if the waste was not properly treated. In Malaysia, 85% of palm oil mill used the ponding system as their preferable treatment method for POME, which later will be discharged into the nearby river. Numerous studies have shown that bacterial population are highly dynamic and can differ strongly in their response to resource availability such as organic carbon, nitrogen and phosphorus. Hence, the loss or changes of microbial diversity is considered a major threat because of its important for ecosystem functions. To date, little is known about microbial communities involved in the polluted river due to POME, either their structural and functional diversity or their response to environmental constraints. Therefore, this study aims to identify and compare the bacterial community structure and function present in the effluent-receiving river located near palm oil mill. The PCR-DGGE and Illumina Miseq have been used in analysing the microbial community structures, whereas the nucleic acid double staining (NADS) assay based on flow cytometry has been used in assessing the microbial community function. The findings demonstrated a significant difference of microbial community present in the upstream and downstream part of the effluent-receiving river water, in relation with the changes of the physicochemical properties. Hence, it is believed that the microbial community that play a key role in biogeochemical processes caused by POME final discharge has the potential to be used as indicator microorganism capable of indicating contamination caused by POME

Shift of low to high nucleic acid bacteria as potential bioindicator for the screening of anthropogenic effects in the receiving river due to palm oil mill effluent final discharge

The microbiological effects of palm oil mill effluent (POME) final discharge upon a receiving river were assessed in this study by using the nucleic acid double staining assay based on flow cytometry. The functional status of the bacterial community at the single-cell level was determined with regards to their abundance, viability and nucleic acid content to monitor the effects of POME final discharge on the affected river. The effluent resulted in the increment of the total cell concentration (TCC) and viable cells which were correlated with the increment of biological oxygen demand (BOD5) and total organic carbon (TOC) concentrations in the receiving river. The shift of low nucleic acid (LNA) to high nucleic acid (HNA) bacterial cells in the affected river suggested the transformation of dormant to active cells due to the POME final discharge. This is the first study to report on the shift of LNA/HNA ratios which may serves as a potential bioindicator in the screening of the anthropogenic effects due to POME final discharge in river water with originally high LNA proportions. Monitoring the effluent discharge at low trophic level using flow cytometry is a rapid and sensitive approach when compared to the current physicochemical assessment method. This approach allows for the screening of river water contamination caused by POME final discharge prior to a full assessment using the recently proposed specific bacterial indicators