ABSTRACT
Background: Despite widespread application of minimally invasive video-assisted thoracic surgery (VATS), postoperative pain following this procedure is still a constant clinical challenge. Serratus anterior plane (SAP) block is one of the regional analgesic techniques with promising outcomes. However, due to the limited duration of action, optimal analgesia is often not achieved with a single injection. We tested whether in patients who have been subjected to routine SAP block under preoperative anesthesia, the addition of a second SAP block 24 hours after surgery, improves quality of recovery, lowers postoperative opioid consumption, and reduces the prevalence of chronic pain. Methods: The present study is a single institutional, prospective, randomized, triple-blinded, placebo-controlled study. Ninety patients undergoing VATS from January 2022 to April 2022 were randomized at 1:1 ratio to receive ultrasound-guided second SAP block with 15 mL 0.375% ropivacaine (SAP block group) or 15 mL normal saline (control group) 24 hours after both groups received routine SAP block with 15 mL 0.375% ropivacaine. The primary outcome was quality of patient recovery, measured using 40-item quality of recovery questionnaire (QoR-40) at postoperative day 2 (POD 2). Secondary outcomes included: postoperative pain scores at rest, postoperative opioid consumptions, number of times that patient controlled analgesia (PCA) pump button was pressed, perioperative complications and adverse effects, prevalence of chronic pain at 2nd and 3rd month postoperatively, and length of hospital stay (LOS). Results: A total of 83 patients completed the study: 43 patients in SAP block group and 40 patients in the control group. The global QoR-40 scores on POD 2 and POD 3 were significantly higher among SAP block group patients (180.07±11.34, 182.09±8.20) compared with the control group (172.18±6.15, 177.50±6.94) (P=0.01, P=0.008) respectively. Postoperative pain scores, opioid consumptions and incidence of postoperative nausea and vomiting were significantly lower among patients in SAP block group versus control group. There were no statistically significant differences in perioperative complications and LOS between the two groups. The prevalence of chronic pain at the 2nd and 3rd month postoperatively for patients in SAP block group and control group was 16.3%, 14%, and 32.5%, 27.5% respectively. Conclusions: In patients undergoing VATS, application of ultrasound-guided second SAP block 24 hours after surgery improved postoperative quality of life, reduced opioid consumption and related side effects, and lowered the prevalence of chronic pain.
ABSTRACT
BACKGROUND: The association between malnutrition and postoperative acute kidney injury (AKI) has not been well studied. In this study, the authors examined the association between preoperative nutritional status and postoperative AKI in older patients who underwent major abdominal surgery, as well as the predictive value of malnutrition for AKI. MATERIALS AND METHODS: The authors retrospectively included patients aged 65 or older who underwent major elective abdominal surgery. The nutritional status of the patient was evaluated using three objective nutritional indices, such as the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT). AKI was determined using the KDIGO criteria. The authors performed logistic regression analysis to investigate the association between preoperative nutritional status and postoperative AKI, as well as the predictive value of nutritional scores for postoperative AKI. RESULTS: A total of 2775 patients were included in the study, of which 707 (25.5%), 291 (10.5%), and 517 (18.6%) had moderate to severe malnutrition according to GNRI, PNI, and CONUT calculations. After surgery, 144 (5.2%) patients developed AKI, 86.1% at stage 1, 11.1% at stage 2, and 2.8% at stage 3 as determined by KDIGO criteria. After adjustment for traditional risk factors, worse nutritional scores were associated with a higher AKI risk. In addition to traditional risk factors, these nutritional indices improved the predictive ability of AKI prediction models, as demonstrated by significant improvements in integrated discrimination and net reclassification. CONCLUSIONS: Poor preoperative nutritional status, as assessed by GNRI, PNI, and CONUT scores, was associated with an increased risk of postoperative AKI. Incorporating these scores into AKI prediction models improved their performance. These findings emphasize the need for screening surgical patients for malnutrition risk. Further research is needed to determine whether preoperative malnutrition assessment and intervention can reduce postoperative AKI incidence.
Subject(s)
Acute Kidney Injury , Malnutrition , Humans , Aged , Nutritional Status , Prognosis , Retrospective Studies , Malnutrition/diagnosis , Malnutrition/epidemiology , Malnutrition/complications , Risk Factors , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiologyABSTRACT
The human body's thermal physiology changes due to atmospheric pressure, which significantly impacts the perception of thermal comfort. To quantify this effect, an improved version of the Predicted Mean Vote model (PMVp), was developed in this study to predict human thermal sensation under low atmospheric pressure conditions. The study employed environmental conditions of 0km/26°C, 3km/26°C, 4km/26°C, and 4km/21°C. Thirteen subjects were continuously monitored for exhaled CO2, inhaled O2, ambient temperature (ta), relative humidity (RH), air velocity (V), black globe temperature (tg), and altitude (H). The predictive performance of PMVp was evaluated by comparing the experimental results from this study with previous experiments. The findings demonstrate that PMVp exhibits lower root-mean-square errors (RMSE) than the original PMV model. Under the four experimental conditions, the RMSE values for PMVp were 0.311, 0.408, 0.123, and 0.375, while those for PMV were 1.251, 1.367, 1.106, and 1.716, respectively. Specifically, at a temperature range of 21â¼27°C (altitude: 941m), the RMSE of PMVp (0.354) was smaller than PMV's. Furthermore, the study analyzed the sensitivity of PMVp to input parameters at an altitude of 4 km. PMVp exhibited considerable sensitivity to the metabolic rate (M) and thermal insulation of clothing (ICL). Consequently, a simple sensitivity scale was established: M>ICL>Ta≈V>Tr>H≈RH, indicating the relative importance of these parameters in influencing PMVp's response. The research findings provide comprehensive knowledge and a useful reference for developing a standard to design and evaluate indoor thermal environments in the plateau region.
Subject(s)
Body Temperature Regulation , Thermosensing , Humans , Temperature , Body Temperature Regulation/physiology , Altitude , ClimateABSTRACT
Recent research has primarily focused on human thermoregulatory responses at high altitudes, but investigations involving extremely high-temperature and hypobaric compound environments are currently lacking. To address this gap in knowledge, this study aimed to enhance the prediction of human heat sensation for pilot reserves while operating in extremely hot cabins with decompression. To achieve this, an improved Predicted Heat Strain (PHS) model was developed by incorporating the influence of air pressure on metabolic rate. The model's validity was assessed through experiments conducted at different altitudes (0m, 5000m, and 8000m) and varying environmental conditions (26°C and 45 °C, 10% RH and 40% RH) within an environmental simulation cabin. During these experiments, local skin temperature, core temperature, heart rate, and blood oxygen saturation were measured. The findings revealed distinct variations in the skin temperature of the hand and foot segments across different experimental stages, and significant correlations were observed between heart rate, core temperature, and local skin temperatures. Furthermore, regression models were established to explore the relationship between heart rate and local skin temperatures. By comparing simulated and experimental core and local skin temperatures, the enhanced PHS model was successfully validated. The conclusions drawn from this study provide valuable insights for predicting thermal physiological indices accurately and conveniently in hot-dry and hypobaric environments.
ABSTRACT
During military operations in high-temperature and relative humidity (RH) conditions, the physiological state and combat capability of pilots are affected severely. In a fighter cockpit, experiments were conducted on thirteen voluntary subjects wearing pilot suits at 21 °C/30%, 30 °C/45%, and 38 °C/60% RH, respectively, in order to examine the physiological changes of pilots in combat thoroughly. The target strike performance, core and skin temperatures, pulse rate, and other parameters were measured and investigated. Significant inter-condition differences were noted in the pulse rate, core temperature, mean skin temperatures, and sweat amount, which increased markedly with elevating temperature and RH. Contrastively, blood oxygen saturation (SpO2) dropped with such elevations. Concerning the skin temperature, the chest and back skin temperatures remained stable, while the temperatures at the hands, feet, and lower arms underwent larger changes with the increasing temperature and humidity. At 38 °C/60% RH, the sweat amount was 3.7 times that at 21 °C/30% RH. The subjects' operational error rates increased as the core temperatures rose, showing high correlations (r2 = 0.81). The results could serve as a theoretical basis for the design of pilot protective equipment and the control of aircraft cockpit temperature.
Subject(s)
Pilots , Hot Temperature , Humans , Humidity , Skin Temperature , TemperatureABSTRACT
Subsequently to the publication of the above paper, the authors have drawn to our attention that, owing to errors made in the compilation of the images in Fig. 6, the images shown in Fig. 6AC in the article were selected incorrectly (essentially, the images shown in Fig. 6A and B were alterative presentations of the same data shown in Fig. 6C). The authors were able to reexamine the original data files and retrieve the correct data panels. The revised version of Fig. 6, featuring the corrected data panels for Fig. 6AC, is shown opposite. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Oncology Reports 36: 2017-2024, 2016; DOI: 10.3892/or.2016.4995].
ABSTRACT
Postoperative cognitive dysfunction (POCD) is a sever postsurgical neurological complication in the elderly population. As the global acceleration of population ageing, POCD is proved to be a great challenge to the present labor market and healthcare system. In the present study, our findings showed that tau acetylation mediated by SIRT1 deficiency resulted in tau hyperphosphorylation in the hippocampus of the aged POCD model and consequently contributed to cognitive impairment. Interestingly, pretreatment with resveratrol almost restored the expression of SIRT1, reduced the levels of acetylated tau and hyperphosphorylated tau in the hippocampus, and improved the cognitive performance in the behavioral tests. What is more, we observed that microglia-derived neuroinflammation resulting from SIRT1 inhibition in microglia probably aggravated the tau acetylation in cultured neurons in vitro. Our findings supported the notion that activation SIRT1 provided dually beneficial effect in the aged POCD model. Taken together, our findings provided the initial evidence that tau acetylation was associated with cognitive impairment in the aged POCD model and paved a promising avenue to prevent POCD by inhibiting tau acetylation in a SIRT1-dependent manner.
Subject(s)
Cognitive Dysfunction/prevention & control , Postoperative Complications/prevention & control , Resveratrol/pharmacology , tau Proteins/metabolism , Acetylation/drug effects , Acetyltransferases/metabolism , Aging/drug effects , Aging/metabolism , Aging/psychology , Anesthesia/adverse effects , Animals , Cells, Cultured , Cognition/drug effects , Cognition/physiology , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Enzyme Activation/drug effects , Hippocampus/drug effects , Hippocampus/metabolism , Male , Mice , Postoperative Complications/metabolism , Postoperative Complications/psychology , Protein Processing, Post-Translational/drug effects , Rats , Rats, Sprague-Dawley , Resveratrol/therapeutic use , Sirtuin 1/metabolism , Surgical Procedures, Operative/adverse effectsABSTRACT
Various lines of evidence suggest that neonatal exposure to general anesthetics, especially repeatedly, results in neuropathological brain changes and long-term cognitive impairment. Although progress has been made in experimental models, the exact mechanism of GA-induced neurotoxicity in the developing brain remains to be clarified. Sirtuin 1 (SIRT1) plays an important role in synaptic plasticity and cognitive performance, and its abnormal reduction is associated with cognitive dysfunction in neurodegenerative diseases. However, the role of SIRT1 in GA-induced neurotoxicity is unclear to date. In this study, we found that the protein level of SIRT1 was inhibited in the hippocampi of developing mice exposed to sevoflurane. Furthermore, the SIRT1 inhibition in hippocampi was associated with brain-derived neurotrophic factor (BDNF) downregulation modulated by methyl-cytosine-phosphate-guanine-binding protein 2 (MeCP2) and cAMP response element-binding protein (CREB). Pretreatment of neonatal mice with resveratrol nearly reversed the reduction in hippocampal SIRT1 expression, which increased the expression of BDNF in developing mice exposed to sevoflurane. Moreover, changes in the levels of CREB and MeCP2, which were considered to interact with BDNF promoter IV, were also rescued by resveratrol. Furthermore, resveratrol improved the cognitive performance in the Morris water maze test of the adult mice with exposure to sevoflurane in the neonatal stage, without changing motor function in the open field test. Taken together, our findings suggested that SIRT1 deficiency regulated BDNF signaling via regulation of the epigenetic activity of MeCP2 and CREB, and resveratrol might be a promising agent for mitigating sevoflurane-induced neurotoxicity in developing mice.
Subject(s)
Antioxidants/therapeutic use , Brain-Derived Neurotrophic Factor/metabolism , Neurotoxicity Syndromes/drug therapy , Resveratrol/therapeutic use , Sevoflurane/adverse effects , Sirtuin 1/metabolism , Animals , Antioxidants/pharmacology , Humans , Male , Mice , Resveratrol/pharmacologyABSTRACT
Postoperative cognitive dysfunction (POCD) is a neurological sequela of surgery and anesthesia. It occurs with high incidence in the aged population. Neuroinflammation is considered one of the least controversial culprits contributing to this postsurgical cognitive impairment, although it is a matter of debate as to why this complication occurs frequently in geriatric individuals. It is unclear how neuroinflammation is activated in aged populations following exposure to anesthesia and surgical procedures. In this study, we investigated the role of sirtuin 1 (SIRT1) in neuroinflammatory priming and cognitive deficits in aged rats after anesthesia and surgery. Our findings demonstrated that the hippocampal expression of SIRT1 decreased with age. The trend of declining SIRT1 expression further deteriorated in aged rats after exposure to anesthesia and surgery. Furthermore, we found that decreased SIRT1 was associated with downregulated expression of DNA methyltransferase 1 (DNMT1) and upregulated acetylated-nuclear factor kappa B (ac-NF-κB) expression, resulting in microglial activation and increased proinflammatory cytokines in the hippocampus of aged rats. Interestingly, our results showed that pretreatment with resveratrol, a SIRT1 agonist, mitigated the neuroinflammatory response and microglial activation and improved cognitive performance in the context fear-conditioning test and Morris water maze. Taken together, our findings suggest that anesthesia and surgery-induced inhibition of hippocampal SIRT1 expression is involved in the activation of neuroinflammation and cognitive impairment in aged rats and that activating SIRT1 might paved a promising path to preventing this postsurgical sequela.
ABSTRACT
The aging population is burgeoning globally and this trend presents great challenges to the current healthcare system as the growing number of aged individuals receives procedures of surgery and anesthesia. Postoperative cognitive dysfunction (POCD) is a severe postoperative neurological sequela. Advanced age is considered as an independent risk factor of POCD. Mounting evidence have shown that neuroinflammation plays an essential role in POCD. However, it remains debatable why this complication occurs highly in the aged individuals. As known, aging itself is the major common high-risk factor for age-associated disorders including diabetes, cardiovascular disease, cancer, and neurodegenerative diseases. Chronic low-grade neuroinflammation (dubbed neuroinflammaging in the present paper) is a hallmark alternation and contributes to age-related cognitive decline in the normal aging. Interestingly, several lines of findings show that the neuroinflammatory pathogenesis of POCD is age-dependent. It suggests that age-related changes, especially the neuroinflammaging, are possibly associated with the postoperative cognitive impairment. Understanding the role of neuroinflammaging in POCD is crucial to elucidate the mechanism of POCD and develop strategies to prevent or treat POCD. Here the focus of this review is on the potential role of neuroinflammaging in the mechanism of POCD. Lastly, we briefly review promising interventions for this neurological sequela.
Subject(s)
Aging/pathology , Cognitive Dysfunction/etiology , Inflammation/complications , Postoperative Complications/etiology , Aged , Animals , Humans , Risk FactorsABSTRACT
BACKGROUND: This study aims to investigate the effects of exogenous interleukin (IL)-37 on the biological characteristics of human lung adenocarcinoma A549 cells and the chemotaxis of regulatory T (Treg) cells. METHODS: After isolating the CD4+ CD25+ Treg cells from the peripheral blood, flow cytometry was used to detect the purity of the Treg cells. A549 cells were divided into blank (no transfection), empty plasmid (transfection with pIRES2-EGFP empty plasmid) or IL-37 group (transfection with pIRES2-EGFP-IL-37 plasmid). RT-PCR was used to detect mRNA expression of IL-37 and ELISA to determine IL-37 and MMP-9 expressions. Western blotting was applied to detect the protein expressions of PCNA, Ki-67, Cyclin D1, CDK4, cleaved caspase-3 and cleaved caspase-9. MTT assay, flow cytometry, scratch test and transwell assay were performed to detect cell proliferation, cycle, apoptosis, migration and invasion. Effect of exogenous IL-37 on the chemotaxis of Treg cells was measured through transwell assay. Xenograft models in nude mice were eastablished to detect the impact of IL-37 on A549 cells. RESULTS: The IL-37 group had a higher IL-37 expression, cell apoptosis in the early stage and percentage of cells in the G0/G1 phase than the blank and empty plasmid groups. The IL-37 group had a lower MMP-9 expression, optical density (OD), percentage of cells in the S and G2/M phases, migration, invasion and chemotaxis of CD4+CD25+ Foxp3+ Treg cells. The xenograft volume and weight of nude mice in the IL-37 group were lower than those in the blank and empty plasmid groups. Compared with the blank and empty plasmid groups, the IL-37 group had significantly reduced expression of PCNA, Ki-67, Cyclin D1 and CDK4 but elevated expression of cleaved caspase-3 and cleaved caspase-9. CONCLUSION: Therefore, exogenous IL-37 inhibits the proliferation, migration and invasion of human lung adenocarcinoma A549 cells as well as the chemotaxis of Treg cells while promoting the apoptosis of A549 cells.
Subject(s)
Chemotaxis/drug effects , Chemotaxis/immunology , Interleukin-1/pharmacology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Adenocarcinoma/genetics , Adenocarcinoma/immunology , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Adolescent , Adult , Animals , Apoptosis/drug effects , Biomarkers , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Female , Humans , Immunophenotyping , Interleukin-1/genetics , Interleukin-1/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/immunology , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Mice , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , T-Lymphocytes, Regulatory/metabolism , Xenograft Model Antitumor Assays , Young AdultABSTRACT
Pyridine, an important chemical raw material, is widely used in industry, for example in textiles, leather, printing, dyeing, etc. In this research, a dielectric barrier discharge (DBD) system was developed to remove pyridine, as a representative type of nitrogen heterocyclic compound in drinking water. First, the influence of the active species inhibitors tertiary butanol alcohol (TBA), HCO3-, and CO32- on the degradation rate of pyridine was investigated to verify the existence of active species produced by the strong ionization discharge in the system. The intermediate and final products generated in the degradation process of pyridine were confirmed and analyzed through a series of analytical techniques, including liquid chromatography-mass spectrometry (LC-MS), high performance liquid chromatography (HPLC), ion chromatography (IC), total organic carbon (TOC) analysis, ultraviolet (UV) spectroscopy, etc. The results showed that the degradation of pyridine was mainly due to the strong oxidizing power of ozone and hydroxyl radical produced by the DBD system. Several intermediate products including 3-hydroxyl pyridine, fumaric acid, 2, 3-dihydroxypyridine, and oxalic acid were detected. Nitrogen was removed from the pyridine molecule to form nitrate. Through analysis of the degradation mechanism of pyridine, the oxidation pathway was deduced. The study provided a theoretical and experimental basis for the application of DBD strong ionization discharge in treatment of nitrogen heterocyclic compounds in drinking water.
Subject(s)
Drinking Water/chemistry , Pyridines/chemistry , Water Pollutants, Chemical/analysis , Water Purification/methods , Pyridines/analysis , Water Pollutants, Chemical/chemistryABSTRACT
INTRODUCTION: Previous randomized controlled trials have led to conflicting findings regarding the effects of nursing interventions on depression of patients with rheumatoid arthritis (RA). The purpose of this study was to use the meta-analytic approach to resolve these discrepancies. METHODS: We performed a systematic search of publications using MEDLINE, EMBASE, the Cochrane Library, and manual searches without language restrictions. Studies that met the following criteria were included: (1) randomized controlled trials; (2) duration of intervention≥4 weeks; (3) comparative control group; (4) adults with RA; (5) published studies in any language since reception; and (6) psychological symptoms assessed. We extracted relative risks (RRs) and 95% confidence internals (CIs) and pooled them using a random effect model. We carried out sensitivity analysis and assessed heterogeneity and publication bias. RESULTS: A total of 14 studies, including 1803 patients, were eligible for inclusion in the review. Depression symptom was assessed by questionnaires. In the pooled analysis, nursing interventions, including exercise training, medication guide, health education and psychotherapy were associated with the remission of depression (RR: -0.67; 95% CI: -0.89 to -0.46; P<0.01) with significant heterogeneity between studies (P<0.01). CONCLUSION: Nursing interventions may be important adjunctive therapies in the medical management of RA patients.
Subject(s)
Arthritis, Rheumatoid/psychology , Depression/nursing , Depression/therapy , Randomized Controlled Trials as Topic , Depression/psychology , Exercise , Health Education , Humans , PsychotherapyABSTRACT
In the present study, we aimed to investigate the effects of CC chemokine ligand 22 (CCL22) and interleukin-37 (IL-37) on the proliferation and epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) A549 cells. pDsRed-CCL22 and pEGFP-IL-37 plasmids were constructed. A549 cells were divided into six groups: the control, the pDsRed-N1 blank plasmid, the pEGFP-C1 blank plasmid, the pDsRed-CCL22 plasmid, the pEGFPIL-37 plasmid and the pDsRed-CCL22 + pEGFP-IL-37 plasmid group. Expression levels and localization of CCL22 and IL-37 in cells were detected by confocal microscopy. Phase-contrast microscopy was applied for observing cellular morphology. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used for detecting the mRNA levels of vimentin, N-cadherin and E-cadherin, and their protein expression levels were tested using western blotting. Constructed plasmids expressed CCL22 and IL-37, both of which had a co-localization in the cell membrane. MTT assay and cell observation results revealed that CCL22 and IL-37 inhibited the proliferation and EMT process of the A549 cells. The results of RT-qPCR and western blotting revealed that decreased vimentin and N-cadherin mRNA and protein expression levels, and increased E-cadherin mRNA and protein expression levels were found in the pDsRed-CCL22 plasmid, pEGFP-IL-37 plasmid and pDsRedCCL22 + pEGFPIL-37 plasmid groups when compared with the control, the pDsRed-N1 blank plasmid and the pEGFP-C1 blank plasmid groups (all P<0.05), and decreased vimentin and N-cadherin mRNA and protein expression levels and increased E-cadherin mRNA and protein expression levels were found in the pDsRedCCL22 + pEGFPIL-37 plasmid group when compared with the pDsRed-CCL22 plasmid and the pEGFPIL-37 plasmid groups (all P<0.05). CCL22 and IL-37 with a co-localization in the A549 cells inhibited the proliferation and EMT process in A549 cells. The antitumor effects of CCL22 and IL37 provide a strategy for the treatment of NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Chemokine CCL22/metabolism , Epithelial-Mesenchymal Transition/physiology , Interleukin-1/metabolism , Lung Neoplasms/pathology , A549 Cells , Blotting, Western , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Proliferation/physiology , Humans , Lung Neoplasms/metabolism , Microscopy, Confocal , Real-Time Polymerase Chain ReactionABSTRACT
Strain specific mouse brain magnetic resonance imaging (MRI) atlases provide coordinate space linked anatomical registration. This allows longitudinal quantitative analyses of neuroanatomical volumes and imaging metrics for assessing the role played by aging and disease to the central nervous system. As NOD/scid-IL-2Rγ(c)(null) (NSG) mice allow human cell transplantation to study human disease, these animals are used to assess brain morphology. Manganese enhanced MRI (MEMRI) improves contrasts amongst brain components and as such can greatly help identifying a broad number of structures on MRI. To this end, NSG adult mouse brains were imaged in vivo on a 7.0 Tesla MR scanner at an isotropic resolution of 100 µm. A population averaged brain of 19 mice was generated using an iterative alignment algorithm. MEMRI provided sufficient contrast permitting 41 brain structures to be manually labeled. Volumes of 7 humanized mice brain structures were measured by atlas-based segmentation and compared against non-humanized controls. The humanized NSG mice brain volumes were smaller than controls (p < 0.001). Many brain structures of humanized mice were significantly smaller than controls. We posit that the irradiation and cell grafting involved in the creation of humanized mice were responsible for the morphological differences. Six NSG mice without MnCl2 administration were scanned with high resolution T2-weighted MRI and segmented to test broad utility of the atlas.
Subject(s)
Anatomy, Artistic , Atlases as Topic , Brain/anatomy & histology , Magnetic Resonance Imaging/methods , Models, Animal , Algorithms , Animals , Contrast Media , Hematopoietic Stem Cell Transplantation , Humans , Male , Manganese , Mice , Mice, Inbred NOD , Mice, SCIDABSTRACT
BACKGROUND: Manganese (Mn(2+))-enhanced MRI (MEMRI) is a valuable imaging tool to study brain structure and function in normal and diseased small animals. The brain retention of Mn(2+) is relatively long with a half-life (t1/2) of 51-74 days causing a slow decline of MRI signal enhancement following Mn(2+) administration. Such slow decline limits using repeated MEMRI to follow the central nervous system longitudinally in weeks or months. This is because residual Mn(2+) from preceding administrations can confound the interpretation of imaging results. We investigated whether the Mn(2+) enhancement decline could be accelerated thus enabling repeated MEMRI, and as a consequence broadens the utility of MEMRI tests. NEW METHODS: We investigated whether N-acetyl-para-aminosalicylic acid (AcPAS), a chelator of Mn(2+), could affect the decline of Mn(2+) induced MRI enhancement in brain. RESULTS AND CONCLUSION: Two-week treatment with AcPAS (200mg/kg/dose×3 daily) accelerated the decline of Mn(2+) induced enhancement in MRI. In the whole brain on average the enhancement declined from 100% to 17% in AcPAS treated mice, while in PBS controls the decline is from 100% to 27%. We posit that AcPAS could enhance MEMRI utility for evaluating brain biology in small animals. COMPARISON WITH EXISTING METHODS: To the best of our knowledge, no method exists to accelerate the decline of the Mn(2+) induced MRI enhancement for repeated MEMRI tests.
Subject(s)
Aminosalicylic Acids/pharmacology , Brain Mapping , Brain/anatomy & histology , Brain/drug effects , Chlorides/pharmacology , Magnetic Resonance Imaging , Manganese Compounds/pharmacology , Aminosalicylic Acids/metabolism , Animals , Brain/metabolism , Chromatography, High Pressure Liquid , Drug Synergism , Image Processing, Computer-Assisted , Mice , Mice, Inbred C57BL , Time FactorsABSTRACT
Toll-like receptor (TLRs) is a type of pattern-recognition receptor that recognizes pathogen-associated molecular patterns, the important mediator of innate immunity. The aim of this study was to examine the anti-inflammatory effect of TLR2 monoclonal antibody (TLR2 mAb) on concanavalin A (ConA) induced-hepatitis. Our in vitro findings indicated that the TLR2 monoclonal antibody developed by us was able to neutralize the activation of peripherial blood mononucleated cells (PBMC) induced by ConA. Furthermore, pretreatment of mice with TLR2 antibody exerted liver protection against ConA. Compared with the isotype IgG group, the TLR2-antibody-treated group demonstrated less mortality with concomitant decreased serum level of Ast and Alt. The detailed mechanisms underlying the protection effect induced by TLR2 antibody was due to inhibition of infiltration of lymphocytes in liver induced by ConA as well as the expression of pro-inflammatory factors, such as TNF-α, IFN-γ, IL-6. Taken together, our findings demonstrated that TLR2 mAb pretreatment protected liver against ConA-induced hepatitis in mice, suggesting that TLR2 mAb is a potential candidate for therapy of acute hepatitis.
Subject(s)
Antibodies, Blocking/administration & dosage , Chemical and Drug Induced Liver Injury/therapy , Immunotherapy/methods , Animals , Antibodies, Blocking/pharmacology , Cell Movement/drug effects , Cells, Cultured , Chemical and Drug Induced Liver Injury/immunology , Concanavalin A/administration & dosage , Cytokines/metabolism , Female , Humans , Inflammation Mediators/metabolism , Mice , Mice, Inbred BALB C , Models, Animal , Toll-Like Receptor 2/antagonists & inhibitorsABSTRACT
Research directed at anatomical, integrative and functional activities of the central nervous system (CNS) can be realized through bioimaging. A wealth of data now demonstrates the utility of magnetic resonance imaging (MRI) towards unraveling complex neural connectivity operative in health and disease. A means to improve MRI sensitivity is through contrast agents and notably manganese (Mn²âº). The Mn²âº ions enter neurons through voltage-gated calcium channels and unlike other contrast agents such as gadolinium, iron oxide, iron platinum and imaging proteins, provide unique insights into brain physiology. Nonetheless, a critical question that remains is the brain target cells serving as sources for the signal of Mn²âº enhanced MRI (MEMRI). To this end, we investigated MEMRI's abilities to detect glial (astrocyte and microglia) and neuronal activation signals following treatment with known inflammatory inducing agents. The idea is to distinguish between gliosis (glial activation) and neuronal injury for the MEMRI signal and as such use the agent as a marker for neural activity in inflammatory and degenerative disease. We now demonstrate that glial inflammation facilitates Mn²âº neuronal ion uptake. Glial Mn²âº content was not linked to its activation. MEMRI performed on mice injected intracranially with lipopolysaccharide was associated with increased neuronal activity. These results support the notion that MEMRI reflects neuronal excitotoxicity and impairment that can occur through a range of insults including neuroinflammation. We conclude that the MEMRI signal enhancement is induced by inflammation stimulating neuronal Mn²âº uptake.
Subject(s)
Magnetic Resonance Imaging/methods , Manganese/physiology , Neuroglia/metabolism , Neurons/metabolism , Neurons/pathology , Animals , Animals, Newborn , Coculture Techniques , Male , Mice , Mice, Inbred C57BL , Mice, Inbred NOD , Mice, SCID , Neurons/physiology , PC12 Cells , Rats , Up-Regulation/physiologyABSTRACT
OBJECTIVE: The physiological sensation of pain and rapid response to stimuli serve as an adaptive way to avoid harmful situations. Our purpose was to investigate why this protection disappears or almost disappears for patients with congenital indifference to pain (CIP). DESIGN: The study was designed as a case report by scanning the candidate genes within CIP patients. SETTING: The study was set at the Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. PATIENTS: We reported patients from two Chinese families that showed insensitivity to pain and were diagnosed with CIP by a neurologist. Different from recently reported studies, our patients were not entirely painless, but demonstrated little pain sensation from injuries. MEASURES: The measures made were novel mutations within SCN9A. RESULTS: Sequence analysis of candidate genes of two affected individuals identified two novel heterozygous mutations (M899I and M932L) in the SCN9A gene. Furthermore, a novel nonsynonymous single-nucleotide polymorphism (SNP) within the SCN9A gene was revealed in affected proband and several unaffected family members. This polymorphism (c. 3312G&T, which produces the amino acid substitution V1104L in human Nav1.7), is present in 6.5% of healthy Chinese. CONCLUSIONS: We speculate that the mutations may be the cause of partial deletion of pain perceptionin in our probands, and the novel polymorphism V1104L may have a predictive role in the pain sensation of healthy individuals.