ABSTRACT
Objective: To explore correlative factors and construct predictive model of intestinal flora imbalance in patients with acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Methods: The patients in acute exacerbation stage of COPD (AECOPD) hospitalized in Yixing People's Hospital from January 1 to December 31, 2019 were included. According to the clinical symptoms and results of fecal examination, the subjects were divided into case group (n=45) and control group (n=83). Multivariate logistic regression was used to analyze the correlative factors of intestinal flora imbalance in AECOPD patients. The prediction model of intestinal flora imbalance in patients with AECOPD was constructed according to the results of factor logistic regression analysis, and the effectiveness of the prediction model was evaluated by receiver operating characteristic (ROC) curve analysis. Results: The ages of subjects in case group and control group were (76±9) and (74±8) years old, respectively, among which males accounted for 80.0% (36/45) and 69.9% (58/83), respectively. The multivariate logistic regression model analysis showed that serum albumin concentration, frequency of acute exacerbation ≥2 times/year, complicated with chronic cor pulmonale and diabetes mellitus were correlative factors of intestinal flora imbalance in patients with AECOPD. The OR (95%CI) were 0.98 (0.80-0.97), 3.70 (1.79-11.72), 2.62 (1.46-10.80) and 3.85 (1.17-8.58), respectively. The prediction model of intestinal flora imbalance was logit P=3.858-0.13×serum albumin consentration+1.52×acute exacerbation ≥2 times/year+1.379×chronic cor pulmonale+1.155×diabetes mellitus. The area under the ROC curve of this model was 0.847 and the sensitivity and specificity of the prediction model were 88.9% and 71.1%, respectively. Conclusions: Serum albumin, frequency of acute exacerbation ≥2 times/year, complicated with chronic cor pulmonale and diabetes mellitus are correlative factors of intestinal flora imbalance in patients with AECOPD. The predictive model shows high clinical value in predicting intestinal flora imbalance in patients with AECOPD.
Subject(s)
Gastrointestinal Microbiome , Pulmonary Disease, Chronic Obstructive , Aged , Aged, 80 and over , Disease Progression , Factor Analysis, Statistical , Humans , Logistic Models , Male , ROC CurveABSTRACT
Objective: To evaluate the effectiveness and safety of transurethral bipolar plasmakinetic prostatectomy in the treatment of benign prostatic hyperplasia in high-risk and senior patients in China. Methods: The PubMed, Cochrane Library, CBM, CNKI and WanFang databases were searched with computer for collecting relevant interventional case series from establishment dates to September 14, 2018. After quality evaluation and data extraction independently conducted by two authors, the Meta-analysis was performed using the Comprehensive Meta-analysis V2 software. Results: Eighteen studies involving 1 899 patients are included. Maximum flow rate increased to 12.28 ml/s (95%CI: 8.42-16.14), 12.88 ml/s (95%CI: 9.85-15.92) ,14.32 ml/s (95%CI: 10.47-18.18), 14.93 ml/s (95%CI: 10.19-19.67) and 20.00 ml/s (95%CI: 19.08-20.92) in 1, 3, 6, 12 and 24 months after surgery, respectively. International prostate symptom score decreased to -18.60 (95%CI: -23.20--14.00), -17.62 (95%CI: -20.21--15.03), -19.14 (95%CI: -20.70--17.59), -19.06 (95%CI: -21.53--16.60) and -22.90 (95%CI: -24.26--21.54), respectively. Quality of life decreased to -2.38 (95%CI: -4.26--0.50), -3.39 (95%CI: -4.57--2.21),-3.75 (95%CI: -4.14--3.36), -3.36(95%CI: -4.56--2.16), and -4.58(95%CI: -4.75--4.41). Post void residual decreased to -231.16 ml (95%CI: -288.30--174.01), -76.10 ml (95%CI: -116.71--35.50), -159.90 ml(95%CI: -207.21--112.59) and -87.70 ml (95%CI: -91.91--83.48). The event rate of postoperative adverse reactions all were not high. Conclusion: Transurethral bipolar plasmakinetic prostatectomy has better clinical efficacy and no obvious side effects in the treatment of benign prostatic hyperplasia in high-risk and senior patients in China.
Subject(s)
Bipolar Disorder , Prostatic Hyperplasia , Transurethral Resection of Prostate , China , Humans , Male , Prostatectomy , Quality of Life , Treatment OutcomeABSTRACT
In this study, a Bayesian risk-induced interval stochastic modeling framework (BRISF) is proposed for planning effluent trading program among point and nonpoint sources as well as identifying interactions of important trading factors under system risk. BRISF incorporates nutrient fate modeling with soil and water assessment tool (SWAT), Bayesian inference with random walk Metropolis algorithm (RWM), and constraint-violation risk-based two-stage stochastic programming (CRTSP) within a general framework. Bayesian inference is employed for uncertainty analysis of SWAT model parameters and uncertain prediction of nutrient loadings; this process provides the random inputs for optimization process. CRTSP is capable of dealing with multiple uncertainties in modeling effluent trading program as well as system risk of environmental allowance violation. BRISF is applied to a real case of Xiangxihe watershed in China for water quality management. Solutions for optimal trading scheme corresponding to different risk levels are generated. Thousands of scenarios are examined to analyze the individual and interactive effects of trading ratios and treatment rates on trading system. Comparison between cross-industry and intra-industry effluent trading scheme is also conducted. It is proved that cross-industry trading would bring about higher benefit with reduced pollution loading; cross-industry effluent trading scheme would be recommended to achieve optimal water quality management and system benefit.
Subject(s)
Environmental Monitoring , Water Pollution/prevention & control , Water Quality , Bayes Theorem , China , Models, Theoretical , Soil , Uncertainty , Water Pollution/economics , Water Pollution/statistics & numerical dataABSTRACT
AIM: To investigate nurses' knowledge, attitudes and practices related to physical restraint in tertiary hospitals and identify the factors that influence physical restraint use. BACKGROUND: Physical restraint is used to maintain patient safety. Nurses play an important role in the restraint process. It is important to identify their understanding, feelings and approach regarding the use of physical restraint. INTRODUCTION: Physical restraint is widely practiced in hospitals in China. However, it results in a range of serious negative consequences. This article provides a clear description of nurses' knowledge, attitudes and practices related to physical restraint. METHODS: A cross-sectional survey was conducted. The participants were asked to complete a questionnaire examining their knowledge, attitudes and practices related to physical restraint use. A total of 200 questionnaires were distributed in four tertiary hospitals in Hubei Province, China between August and October 2014. RESULTS: The nurses' responses indicated a good level of knowledge regarding physical restraint use. However, they held some misconceptions. The nurses' attitudes towards physical restraint tended to be neutral. The nurses were well experienced in the use of physical restraint. Nurses who had received on-the-job training performed better than those who had received no training related to knowledge and practices regarding physical restraint use. CONCLUSIONS AND IMPLICATION FOR NURSING/HEALTH POLICY: In-service training is highly recommended for nursing managers to improve nurses' physical restraint related knowledge and practices. Regulations regarding the use of restraints should be established as soon as possible by healthcare administration system. IMPLICATIONS FOR NURSING: Nurses should be open to evaluate and improve their views and attitudes regarding effective physical restraint use via multidimensional interventions.
Subject(s)
Attitude of Health Personnel , Health Knowledge, Attitudes, Practice , Nursing Staff, Hospital/psychology , Restraint, Physical/psychology , Adult , China , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , Tertiary Care Centers , Young AdultABSTRACT
Objective: To systematically evaluate the quality of clinical practice guidelines for the diagnosis and treatment of benign prostatic hyperplasia (BPH), and to compare the context of recommendations in order to provide references for clinical application. Methods: We searched databases such as the National Guideline Clearinghouse (NGC), Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN) and World Health Organization (WHO), PubMed, Embase, CNKI, VIP, WanFang Data, CBM, and Medlive from their establishment until August 13, 2016, to collect evidence-based guidelines and/or consensus on BPH. Method: Methodological quality of included guidelines was assessed according to the AGREE â ¡ instrument, and differences and similarities among recommendations were compared. Results: A total of 15 guidelines were included. According to the AGREE â ¡ instrument, the score of scope and purpose, stakeholder involvement, rigour of formulate, clarity of presentation, applicability, and editorial independence was 72%, 38%, 30%, 58%, 16%, and 40%, respectively. The recommendations of different guidelines were basically similar, only with conflicts in some areas. Conclusions: The quality of included guidelines remains to be unified, the context of them can provide valuable implications for development or improvement.
Subject(s)
Prostatic Hyperplasia/diagnosis , Consensus , Evidence-Based Medicine , Humans , Male , Practice Guidelines as TopicABSTRACT
Objective: To understand the current situation and trend on the relations between erectile dysfunction (ED) and cardiovascular disease (CVD) through analyzing the epidemiologic research data. Methods: We conducted a literature search on the Scopus for potentially relevant epidemiologic studies on ED and CVD published from 1957 to October, 28, 2016. Age of the article, types, regions, citation, and co-authorship of the documents were recorded. Results: A total number of 412 pieces of literature were published in the past six decades, with original articles the most common types of ED and CVD. ED and CVD associated epidemiologic topics had an annual increase in number, and remained stable in the past decade, with occident countries as the United States and Italy taking the lead in this area. Clinical and epidemiological studies were the hottest areas, with most authors sharing a co-authorship. Conclusion: Our results suggested that inter-disciplinary cooperation with emphasize on clinical application were the effective starting points for ED and CVD associated epidemiologic studies.
Subject(s)
Cardiovascular Diseases/physiopathology , Arteries/physiopathology , Bibliometrics , Erectile Dysfunction/physiopathology , Humans , MaleABSTRACT
In recent years, increscent emissions in the city of Beijing due to expanded population, accelerated industrialization and inter-regional pollutant transportation have led to hazardous atmospheric pollution issues. Although a number of anthropogenic control measures have been put into use, frequent/severe haze events have still challenged regional governments. In this study, a hybrid population-production-pollution nexus model (PPP) is proposed for air pollution management and air quality planning (AMP) with the aim to coordinate human activities and environmental protection. A fuzzy-stochastic mixed quadratic programming method (FSQ) is developed and introduced into a PPP for tackling atmospheric pollution issues with uncertainties. Based on the contribution of an index of population-production-pollution, a hybrid PPP-based AMP model that considers employment structure, industrial layout pattern, production mode, pollutant purification efficiency and a pollution mitigation scheme have been applied in Beijing. Results of the adjustment of employment structure, pollution mitigation scheme, and green gross domestic product under various environmental regulation scenarios are obtained and analyzed. This study can facilitate the identification of optimized policies for alleviating population-production-emission conflict in the study region, as well as ameliorating the hazardous air pollution crisis at an urban level.
Subject(s)
Air Pollutants , Environmental Monitoring , Air Pollution , Beijing , China , Cities , Humans , Particulate MatterABSTRACT
Meta-analysis used for genetic association studies became popular among researchers, with the amount of published papers increased rapidly. In this paper, we will focus on the introduction on the selection of genetic models. Traditionally, methods used for Meta-analysis on genetic association studies was to calculate the statistics based on available genetic models which not only increasing the probability of false-positives but also making the interpretation of results more difficult. Hence, a critical step in the Meta-analysis of genetic association studies was to choose the appropriate inheritance model. The aim of this paper was to introduce the theory of Bayesian analysis regarding the genetic model-free approach, in performing the Meta-analysis for studies related to genetic associations.
Subject(s)
Bayes Theorem , Genetic Association Studies , Models, Genetic , Genetic Predisposition to Disease , Humans , Polymorphism, Single Nucleotide , ProbabilityABSTRACT
The tumor necrosis factor-alpha (TNF-α) G-308A polymorphism has been suggested to be a susceptibility factor for myocardial infarction (MI). However, differing results from various studies have led to controversial conclusions. Hence, we performed a meta-analysis to evaluate the association between TNF-α G-308A polymorphism and MI. Reported studies published before March 30, 2015 were included and analyzed from the PubMed and Embase databases. Study selection and data extraction were carried out independently by two authors. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association between the selected variables using the Comprehensive Meta-Analysis v2.2 software. In total, 12 publications with 13 case-control studies consisting of 6037 cases and 7262 controls were included in our meta-analysis. The overall results showed that there was no significant association between TNF-α G-308A polymorphism and MI risk [A vs G: OR = 1.18, 95%CI = 0.94-1.48; AA vs GG: OR = 1.23, 95%CI = 0.74-2.05; GA vs GG: OR = 1.22, 95%CI = 0.98-1.51; (GA+AA) vs G: OR = 1.21, 95%CI = 0.96-1.54; AA vs (GG+GA): OR = 1.16, 95%CI = 0.72-1.88]. However, when subgroup analysis was performed according to the stages of MI, results indicated that there was a significant association between TNF-α G-308A polymorphism and the risk of acute MI. Other subgroup analyses revealed no significant associations. Current evidence suggests that TNF-α G-308A polymorphism may be associated with increased risk for acute MI.
Subject(s)
Genetic Predisposition to Disease , Myocardial Infarction/genetics , Polymorphism, Single Nucleotide , Tumor Necrosis Factor-alpha/genetics , Case-Control Studies , Gene Expression , Humans , Myocardial Infarction/diagnosis , Myocardial Infarction/pathology , Odds Ratio , Risk FactorsABSTRACT
This study developed a fuzzy-stochastic programming with Green Z-score criterion (FSGZ) method for water resources allocation and water quality management with a trading-mechanism (WAQT) under uncertainties. FSGZ can handle uncertainties expressed as probability distributions, and it can also quantify objective/subjective fuzziness in the decision-making process. Risk-averse attitudes and robustness coefficient are joined to express the relationship between the expected target and outcome under various risk preferences of decision makers and systemic robustness. The developed method is applied to a real-world case of WAQT in the Kaidu-Kongque River Basin in northwest China, where an effective mechanism (e.g., market trading) to simultaneously confront severely diminished water availability and degraded water quality is required. Results of water transaction amounts, water allocation patterns, pollution mitigation schemes, and system benefits under various scenarios are analyzed, which indicate that a trading-mechanism is a more sustainable method to manage water-environment crisis in the study region. Additionally, consideration of anthropogenic (e.g., a risk-averse attitude) and systemic factors (e.g., the robustness coefficient) can support the generation of a robust plan associated with risk control for WAQT when uncertainty is present. These findings assist local policy and decision makers to gain insights into water-environment capacity planning to balance the basin's social and economic growth with protecting the region's ecosystems.
Subject(s)
Models, Theoretical , Water Pollution , Water Quality , Water Resources , Water Supply , China , Decision Making , Fuzzy Logic , Probability , Risk , UncertaintyABSTRACT
In this study, an interval-stochastic-based risk analysis (RSRA) method is developed for supporting river water quality management in a rural system under uncertainty (i.e., uncertainties exist in a number of system components as well as their interrelationships). The RSRA method is effective in risk management and policy analysis, particularly when the inputs (such as allowable pollutant discharge and pollutant discharge rate) are expressed as probability distributions and interval values. Moreover, decision-makers' attitudes towards system risk can be reflected using a restricted resource measure by controlling the variability of the recourse cost. The RSRA method is then applied to a real case of water quality management in the Heshui River Basin (a rural area of China), where chemical oxygen demand (COD), total nitrogen (TN), total phosphorus (TP), and soil loss are selected as major indicators to identify the water pollution control strategies. Results reveal that uncertainties and risk attitudes have significant effects on both pollutant discharge and system benefit. A high risk measure level can lead to a reduced system benefit; however, this reduction also corresponds to raised system reliability. Results also disclose that (a) agriculture is the dominant contributor to soil loss, TN, and TP loads, and abatement actions should be mainly carried out for paddy and dry farms; (b) livestock husbandry is the main COD discharger, and abatement measures should be mainly conducted for poultry farm; (c) fishery accounts for a high percentage of TN, TP, and COD discharges but a has low percentage of overall net benefit, and it may be beneficial to cease fishery activities in the basin. The findings can facilitate the local authority in identifying desired pollution control strategies with the tradeoff between socioeconomic development and environmental sustainability.
Subject(s)
Environmental Monitoring/methods , Rivers/chemistry , Water Pollutants, Chemical/analysis , Water Pollution/prevention & control , Biological Oxygen Demand Analysis , China , Cities , Nitrogen/analysis , Phosphorus/analysis , Reproducibility of Results , Water Pollution/analysis , Water QualityABSTRACT
AIM: To determine and compare the diagnostic value of computed tomography (CT)-guided percutaneous core needle biopsy (PCNB) and percutaneous fine-needle aspiration biopsy (PNAB) in pulmonary lesions. MATERIALS AND METHODS: PubMed, EMBASE, and the Web of Science were systematically searched for relevant studies that investigated the diagnostic accuracy of CT-guided PCNB and/or PNAB for pulmonary lesions up to December 2014. After study selection, data extraction, and quality assessment, the sensitivity (SEN), specificity (SPE), diagnostic odds rate (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and summary receiver operating characteristic (SROC) curves were calculated using the Meta-Disc 1.4 software. RESULTS: Nineteen publications, including 21 independent studies, met the inclusion criteria. Of them, 15 studies were included in the PCNB group and six studies in the PNAB group. The pooled SEN, SPE, DOR, PLR, NLR, and SROC were 0.95, 0.99, 54.72, 0.06, 821.90, and 0.98 in the PCNB group and 0.90, 0.99, 24.71, 0.14, 210.72, and 0.98 in the PNAB group, respectively. CONCLUSION: Based on current evidence, both PCNB and PNAB can be used as diagnostic methods to distinguish benign and malignant pulmonary lesions; the difference between PCNB and PNAB regarding diagnostic accuracy of benign or malignant pulmonary lesions is not obvious.
Subject(s)
Biopsy, Fine-Needle , Biopsy, Large-Core Needle , Image-Guided Biopsy , Lung Diseases/pathology , Tomography, X-Ray Computed/methods , Diagnosis, Differential , Humans , Lung Diseases/diagnostic imaging , Sensitivity and SpecificityABSTRACT
This review aimed to evaluate the clinical outcome of different lasers management on orthodontic pain. Cochrane Library (Issue 7, 2014) and MEDLINE (1966-2014.7) were searched to collect randomized controlled trials on lasers for orthodontic pain. Studies meeting the inclusion criteria were systematically evaluated. The Cochrane Collaboration tools RevMan5.1.7 and GRADEpro 3.6 were used in this systematic review and meta-analysis. As a result, 11 randomized controlled trials (RCTs) studying on low-level laser therapy (LLLT) for orthodontic pain control were included. Meta-analysis and risk of bias assessment were implemented using RevMan5.1.7, and level of evidence assessments was measured by GRADEpro 3.6. In the outcome of the score of the most painful day, the comparison of laser versus placebo (pain associated with tooth movement) demonstrated that LLLT reduced the pain score significantly compared with placebo groups (MD = -4.39, 95% CI range -5.9--2.88, P < 0.00001). In the same way, the most painful day was significantly brought forward in laser versus control group (MD = -0.42, 95% CI range -0.74--0.10, P = 0.009). Furthermore, the outcome of the end of pain day showed a trend of pain termination earlier in laser versus control and placebo groups, but without statistical significance (MD = -1.37, 95% CI range -3.37-0.64, P = 0.18 and MD = -1.04, 95% CI range -4.22-2.15, P = 0.52). However, for the reason of downgrade factors, all the GRADE level of evidences of eight comparisons for three outcomes showed a very low quality. Therefore, for the methodological shortcomings and risk of bias of RCTs included, insufficient evidence was submitted to judge whether LLLT was effective in relieving orthodontic pain. Further and more perfect researches should be done in order to recommend LLLT as a routine method for orthodontic pain.
Subject(s)
Low-Level Light Therapy/methods , Pain/radiotherapy , Adolescent , Adult , Child , Female , Humans , Lasers , Male , Pain Management , Placebos , Young AdultABSTRACT
Magnesium (Mg) ions were incorporated into fluoridated hydroxyapatite (HA) coating by the sol-gel dip-coating method. Mg in the coating was measured by x-ray photoelectron spectroscopy (XPS). The changes of calcium and magnesium concentrations were recorded to monitor the dissolution behavior of the coatings. In vitro cell responses were evaluated using MG63 cells in terms of cell morphology, proliferation and differentiation. The substitution of Mg and F ions into the HA crystal structure was confirmed by XPS. Only a limited amount of Mg can be incorporated into HA lattice. The dissolution test revealed that Mg incorporation increased the solubility of the coating in the tris-buffered saline solution. The highest solubility was achieved at x = 1.5 (Ca((10-x))Mg(x)(PO(4))(6) F(OH). In the cell culture test, well-spread cells were observed on all the coatings. Also, a significantly positive effect of Mg ions on cell proliferation and late differentiation was found at x = 1.5. Mg incorporation stimulates osteoblastic cell responses on fluoridated hydroxyapatite coatings.
Subject(s)
Hydroxyapatites/chemistry , Ions/pharmacology , Magnesium/pharmacology , Osteoblasts/cytology , Calcium/analysis , Calcium/pharmacology , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Electron Probe Microanalysis , Gels/pharmacology , Humans , Osteoblasts/drug effects , Osteoblasts/physiology , SolubilityABSTRACT
Bio-compatible ZnO nanocrystals doped with Co, Cu and Ni cations, surface capped with two types of aminosilanes and titania are synthesized by a soft chemical process. Due to the small particle size (2-5 nm), surface functional groups and the high photoluminescence emissions at the UV and blue-violet wavelength ranges, bio-imaging on human osteosarcoma (Mg-63) cells and histiocytic lymphoma U-937 monocyte cells showed blue emission at the nucleus and bright turquoise emission at the cytoplasm simultaneously. This is the first report on dual-color bio-images labeled by one semiconductor nanocrystal colloidal solution. Bright green emission was detected on mung bean seedlings labeled by all the synthesized ZnO nanocrystals. Cytotoxicity tests showed that the aminosilanes capped nanoparticles are non-toxic. Quantum yields of the nanocrystals varied from 79% to 95%. The results showed the potential of the pure ZnO and Co-doped ZnO nanocrystals for live imaging of both human cells and plant systems.
ABSTRACT
A simple steam-assisted solid phase synthesis method was developed for synthesis of boehmite nanowires in the presence of TEAOH surfactant. The boehmite nanowires had uniform diameters (12-16 nm) and length up to 1-2 microm. The morphology of the nanostructured wires was well preserved after being converted to pure gamma-Al2O3 by thermal treatment at 600 degrees C for 5 h. The nanowires of Al2O3 exhibited excellent thermal stability by retarding the phase transformation and maintaining the wires-like nanostructure after being aged up to 1300 degrees C by preventing sintering between particles at high temperatures. The surface areas of Al2O3 nanowires could be maintained as high as 68 m2/g at 1300 degrees C while the surface areas of Al2O3 micropowder shrank to 0.89 m2/g after same thermal treatment. Both in-situ XRD and 27Al NMR results indicated that the crystal structure of gamma-Al2O3 nanowires was not transformed to alpha-Al2O3 at 1300 degrees C whereas micropowder Al2O3 was fully converted to alpha-Al2O3 at 1100 degrees C.
Subject(s)
Aluminum Oxide/chemistry , Nanoparticles/chemistry , Nanowires/chemistry , Aluminum Hydroxide/chemistry , Crystallization , Hot Temperature , Magnetic Resonance Spectroscopy , Microscopy, Electron, Transmission , Nanotechnology/methods , Powders , Spectrum Analysis, Raman , Temperature , Time Factors , X-Ray DiffractionABSTRACT
The Cl(-)-ATPase/pump in the plasma membrane of the rat brain is a candidate for active outwardly directed Cl(-) translocating systems. We recently isolated a Cl(-) pump, 520- or 580-kDa protein complex, which consisted of 51-, 55-, 60-, and 62-kDa proteins. In this study, we cloned a cDNA encoding a 55-kDa glycoprotein, designated as ClP55, which contained an open reading frame of 1512 base pairs encoding a protein of 504 amino acids including a signal peptide of 28 amino acids. Northern and Western blot analyses demonstrated expression of ClP55 mainly in the cerebrum. Application of antisense phosphorothioate oligonucleotides to cultured neurons resulted in a marked increase in the intracellular Cl(-) concentration ([Cl(-)](i)). Immunohistochemical analysis indicated that ClP55 was localized to the plasma membranes of neurons such as hippocampal pyramidal neurons and cerebellar Purkinje cells. Taken together, these results suggest that ClP55 is one of the Cl(-) pump subunits responsible for Cl(-) pump activity.
Subject(s)
Adenosine Triphosphatases/chemistry , Adenosine Triphosphatases/genetics , Brain/enzymology , Adenosine Triphosphatases/metabolism , Amino Acid Sequence , Animals , Anion Transport Proteins , Base Sequence , Blotting, Northern , Blotting, Western , Cell Membrane/enzymology , Cell Membrane/metabolism , Cells, Cultured , Cerebellum/metabolism , Chlorine/metabolism , Cloning, Molecular , DNA, Complementary/metabolism , Electrophoresis, Polyacrylamide Gel , Glutathione Transferase/metabolism , Hippocampus/embryology , Hippocampus/enzymology , Immunohistochemistry , Microscopy, Fluorescence , Molecular Sequence Data , Neurons/enzymology , Neurons/metabolism , Oligonucleotides, Antisense/chemistry , Open Reading Frames , Protein Processing, Post-Translational , Rats , Rats, Wistar , Recombinant Fusion Proteins/metabolism , Signal Transduction , Telencephalon/enzymology , Tissue Distribution , TransfectionABSTRACT
Cl(-)-ATPase in the CNS is a candidate for an outwardly directed neuronal Cl(-) transporter requiring phosphatidylinositol-4-phosphate (PI4P) for its optimal activity. To test its pathophysiological changes in a phosphatidylinositol (PI) metabolism disorder, the effects of neurotoxic factors in Alzheimer's disease (AD), amyloid beta proteins (Abetas), on the Cl(-)-ATPase activity were examined using primary cultured rat hippocampal neurons. Amyloid beta proteins (1-40, 1-42 and 25-35) concentration-dependently (1-100 nM) and time-dependently (from 1 h to 6 day) decreased Cl(-)-ATPase activity and elevated intracellular Cl(-) concentrations ([Cl(-)]i), Abeta25-35 being the most potent. Addition of inositol or 8-Br-cyclic GMP completely reversed these Abeta-induced changes. The recoveries in enzyme activity were attenuated by an inhibitor of PI 4-kinase, 10 microM wortmannin or 20 microM quercetin, but not by a PI 3-kinase inhibitor, 50 nM wortmannin or 10 microM LY294002. The PI, PIP and PIP2 levels of the plasma membrane-rich fraction were lower in the Abeta-treated cells as compared with each control. In the Abeta-exposed culture, but not in control, stimulation by 10 microM glutamate for 10 min significantly increased fragmentation of DNA and decreased cell viability. Addition of inositol or 8-Br-cyclic GMP prevented the effect of Abeta-treatment on the neurotoxicity of glutamate. Thus, Abetas reduce neuronal Cl(-)-ATPase activity, resulting in an increase in [Cl(-)]i probably by lowering PI4P levels, and this may reflect a pre-apoptotic condition in early pathophysiological profiles of AD.
Subject(s)
Adenosine Triphosphatases/antagonists & inhibitors , Amyloid beta-Peptides/pharmacology , Neurons/drug effects , Peptide Fragments/pharmacology , 8-Bromo Cyclic Adenosine Monophosphate/pharmacology , Adenosine Triphosphatases/metabolism , Alzheimer Disease/physiopathology , Animals , Anion Transport Proteins , Cell Fractionation , Cell Survival/drug effects , Cells, Cultured , Chlorides/metabolism , DNA Fragmentation/drug effects , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Glutamic Acid/pharmacology , Hippocampus/cytology , Humans , Inositol/pharmacology , Neurons/enzymology , Phosphatidylinositol Phosphates/metabolism , Phosphatidylinositols/metabolism , Rats , Rats, Wistar , Time FactorsABSTRACT
Developmental changes in brain Cl(-)-ATPase activity were examined using fetal, neonatal and adult rats. The Cl(-)-ATPase activity rapidly increased over 20 postnatal days to a level four-fold higher than that in an 18-day-old fetus. On Western blot analysis using an anti-Cl(-)-ATPase/pump 51 kDa subunit (ClP51) antibody, the amount of ClP51 protein increased in parallel with Cl(-)-ATPase activity. Immunohistochemistry using the same antibody showed Cl(-)-ATPase-like immunoreactivity on the cell membranes of neurons such as cerebral and hippocampal pyramidal cells and cerebellar Purkinje cells, where the immunoreactivity increased with developmental changes in the size and shape of the neurons. These findings suggest that neuronal Cl(-)-ATPase activity markedly increases during early postnatal development with an increase in the amount of Cl(-)-ATPase protein, which may support the formation of inwardly directed neuronal Cl(-) gradients.