ABSTRACT
OBJECTIVES: Chronic low back pain (CLBP) is one of the most common chronic pain conditions that cause both individual suffering and a burden to society. For these patients, several interventional treatment options such as surgery, blocks, radiofrequency, and spinal cord stimulation are available. Lately, dorsal root ganglion stimulation (DRG-S) also has been mentioned as an option by targeting bilateral T12 dorsal ganglia. In this study, we present the outcome of 11 patients with CLBP treated with bilateral T12 DRG-S. MATERIALS AND METHODS: Thirteen patients with CLBP with and without leg pain were treated with bilateral T12 DRG-S. Three of the patients also received a third lumbar lead owing to leg pain. Eleven of the patients had >50% pain relief during the peri- or/and postoperative testing and received a fully implantable neurostimulator. Pain intensity, general health status, quality of life, pain catastrophizing, mental status, sleeping disorder, physical activity, and patient satisfaction were followed using numeric rating scale (NRS), Patient-Reported Outcomes Measurement Information System 29 version 2.1, Pain Catastrophizing Score, Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire Depression Module, Insomnia Severity Index, and Patient Satisfaction Questionnaire at baseline before implantation and at three months and six months. The results were analyzed on the basis of six domains: pain relief, sleeping disorder, social ability, mental status, physical activity, and satisfaction. To be identified as a responder, the patients should show a significant improvement in the pain relief domain together with at least two other domains. All responders also were given the opportunity to test 4-Hz DRG-S and compare it with traditional 20-Hz stimulation. RESULTS: All 11 patients were identified as responders at six months. Five of the patients had >80% pain relief, with an average NRS score reduction of 71% for the whole group. Significant improvement could be observed in three domains for one patient, four domains for three patients, five domains for six patients, and six domains for one patient. Seven patients chose to try 4-Hz stimulation. All seven identified 4-Hz stimulation as at least as good as or better than 20-Hz stimulation and chose to continue with 4-Hz stimulation. CONCLUSIONS: Bilateral T12 DRG-S seems to be an effective treatment for chronic low back pain, with significant beneficial effect not only on pain but also on quality of life, pain catastrophizing, mental status, sleeping disorder, and physical activity. 4-Hz DRG-S gave a result comparable with or better than 20-Hz stimulation.
Subject(s)
Chronic Pain , Low Back Pain , Spinal Cord Stimulation , Humans , Low Back Pain/therapy , Ganglia, Spinal/physiology , Retrospective Studies , Quality of Life , Pain Management/methods , Treatment Outcome , Chronic Disease , Spinal Cord Stimulation/methods , Chronic Pain/therapyABSTRACT
OBJECTIVES: Intrathecal morphine pump (ITMP) infusion therapy is efficient in managing chronic pain refractory to standard treatment. This study evaluates pain relief and improvement of quality of life in chronic pain patients after intrathecal morphine pump implantation for treatment of persistent pain after lumbar spinal fusion surgery and lumbar spinal decompression alone. METHODS: Forty three chronic pain patients that received an ITMP at our department between 2009 and 2019 were retrospectively analyzed divided into 2 cohorts (lumbar spinal fusion surgery and lumbar spinal decompression alone). Pain intensity was evaluated using the numeric rating scale (NRS), quality of life was assessed by EQ-5D-3L, mental health was assessed by Beck Depression Inventory (BDI-V), and Pain Catastrophizing Scale (PCS). Morphine dosage was assessed over time. Data was collected preoperatively, 6 and 24 months postoperatively. Statistical analysis was performed using Friedman's analysis of variance to evaluate the development of NRS, PCS, BDI and EQ-5D-3L over time and Mann-Whitney-U-test for the differences between these parameters in the different cohorts. A two-sided p-value <0.05 was considered statistically significant. RESULTS: Median age was 64 years (IQR25-75 56-71 years). NRS, EQ-5D-3L, BDI-V, and PCS showed a significant overall improvement after 6 and 24 months compared to baseline data (p<0.001). No statistically significant differences between patients with lumbar spinal fusion surgery and lumbar spinal decompression alone were seen. Furthermore, no statistically significant differences for age and gender were seen. The initially administered median morphine dosage was significantly higher in the fusion group (3.0â¯mg/day; IQR25-75 1.5-4.2â¯mg/day) compared to the decompression-alone group (1.5â¯mg/day; IQR25-75 1.0-2.6â¯mg/day); (p=0.027). CONCLUSIONS: This retrospective study showed that ITMP have a major long-term impact on pain relief, improve the quality of life, psychological distress, as well as pain catastrophizing in patients with chronic pain following lumbar spinal surgery independent of the previous surgical procedure. After ITMP implantation initial median morphine dosage seems to be significantly higher after spinal fusion compared to decompressive surgery alone.
Subject(s)
Chronic Pain , Humans , Middle Aged , Retrospective Studies , Chronic Pain/drug therapy , Chronic Pain/surgery , Morphine , Treatment Outcome , Quality of Life , Lumbar Vertebrae/surgery , DecompressionABSTRACT
Tauopathies are heterogeneous clinicopathological entities characterized by abnormal neuronal and/or glial inclusions of the microtubule-binding protein tau. In secondary tauopathies, i.e., Alzheimer's disease (AD), tau deposition can be observed, but tau may coexist with another protein, i.e., amyloid-ß. In the last 20 years, little progress has been made in developing disease-modifying drugs for primary and secondary tauopathies and available symptomatic drugs have limited efficacy. Treatments are being developed to interfere with the aggregation process or to promote the clearance of tau protein. Several tau-targeted passive immunotherapy approaches are in development for treating tauopathies. At present, 12 anti-tau antibodies have entered clinical trials, and 7 of them are still in clinical testing for primary tauopathies and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, PNT00, and APNmAb005). However, none of these seven agents have reached Phase III. The most advanced anti-tau monoclonal antibody for treating AD is semorinemab, while bepranemab is the only anti-tau monoclonal antibody still in clinical testing for treating progressive supranuclear palsy syndrome. Two other anti-tau monoclonal antibodies have been discontinued for the treatment of primary tauopathies, i.e., gosuranemab and tilavonemab. Further evidence will come from ongoing Phase I/II trials on passive immunotherapeutics for treating primary and secondary tauopathies.
Subject(s)
Alzheimer Disease , Tauopathies , Humans , tau Proteins , Tauopathies/therapy , Antibodies, Monoclonal , Immunization, PassiveABSTRACT
INTRODUCTION: Tauopathies are clinicopathological entities with increased and pathological deposition in glia and/or neurons of hyperphosphorylated aggregates of the microtubule-binding protein tau. In secondary tauopathies, i.e. Alzheimer's disease (AD), tau deposition can be observed, but tau coexists with another protein (amyloid-ß). In the last 20 years, little progress has been made in developing disease-modifying drugs for primary and secondary tauopathies and available symptomatic drugs have limited efficacy. AREAS COVERED: The present review summarized recent advances about the development and challenges in treatments for primary and secondary tauopathies, with a focus on passive tau-based immunotherapy. EXPERT OPINION: Several tau-targeted passive immunotherapeutics are in development for treating tauopathies. At present, 14 anti-tau antibodies have entered clinical trials, and 9 of them are still in clinical testing for progressive supranuclear palsy syndrome and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, APNmAb005, MK-2214, PNT00, and PRX005). However, none of these nine agents have reached Phase III. The most advanced anti-tau monoclonal antibody for treating AD is semorinemab, while bepranemab is the only anti-tau monoclonal antibody still in clinical testing for treating progressive supranuclear palsy syndrome. Further evidence on passive immunotherapeutics for treating primary and secondary tauopathies will come from ongoing Phase I/II trials.
Subject(s)
Alzheimer Disease , Supranuclear Palsy, Progressive , Tauopathies , Humans , Tauopathies/drug therapy , Tauopathies/metabolism , tau Proteins/metabolism , Alzheimer Disease/therapy , Alzheimer Disease/metabolism , Antibodies, Monoclonal/therapeutic use , ImmunotherapyABSTRACT
Studies have shown that targeting xanthine oxidase (XO) can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia. This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato (diacylated AF-PSPs) on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet. The body weight, organ index, serum biochemical indexes, and liver antioxidant indexes of mice were measured, and the kidneys were observed in pathological sections. The relative expression levels of messenger RNAs (mRNAs) of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain (qPCR) reaction technique, and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry (IHC) technique. Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice, and that this effect might be related to the regulation of liver XO activity, lipid accumulation, and relevant renal transporters. Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder, liver lipid accumulation, and liver oxidative stress, thereby enhancing insulin utilization and sensitivity, lowering blood sugar, and reducing hyperglycemia in mice. Also, diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism, and reduced kidney injury and inflammation. This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid (UA) by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.
Subject(s)
Hyperglycemia , Hyperuricemia , Ipomoea batatas , Mice , Animals , Hyperuricemia/chemically induced , Hyperuricemia/drug therapy , Diet, High-Fat/adverse effects , Anthocyanins/pharmacology , Anthocyanins/chemistry , Ipomoea batatas/chemistry , Fructose/adverse effects , Hyperglycemia/drug therapy , LipidsABSTRACT
Studies have shown that targeting xanthine oxidase (XO) can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia. This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato (diacylated AF-PSPs) on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet. The body weight, organ index, serum biochemical indexes, and liver antioxidant indexes of mice were measured, and the kidneys were observed in pathological sections. The relative expression levels of messenger RNAs (mRNAs) of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain (qPCR) reaction technique, and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry (IHC) technique. Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice, and that this effect might be related to the regulation of liver XO activity, lipid accumulation, and relevant renal transporters. Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder, liver lipid accumulation, and liver oxidative stress, thereby enhancing insulin utilization and sensitivity, lowering blood sugar, and reducing hyperglycemia in mice. Also, diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism, and reduced kidney injury and inflammation. This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid (UA) by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.
Subject(s)
Mice , Animals , Hyperuricemia/drug therapy , Diet, High-Fat/adverse effects , Anthocyanins/chemistry , Ipomoea batatas/chemistry , Fructose/adverse effects , Hyperglycemia/drug therapy , LipidsABSTRACT
Spinal cord stimulation (SCS) is an effective and validated treatment to address chronic refractory neuropathic pain in persistent spinal pain syndrome-type 2 (PSPS-T2) patients. Surgical SCS lead placement is traditionally performed under general anesthesia due to its invasiveness. In parallel, recent works have suggested that awake anesthesia (AA), consisting of target controlled intra-venous anesthesia (TCIVA), could be an interesting tool to optimize lead anatomical placement using patient intra-operative feedback. We hypothesized that combining AA with minimal invasive surgery (MIS) could improve SCS outcomes. The goal of this study was to evaluate SCS lead performance (defined by the area of pain adequately covered by paraesthesia generated via SCS), using an intraoperative objective quantitative mapping tool, and secondarily, to assess pain relief, functional improvement and change in quality of life with a composite score. We analyzed data from a prospective multicenter study (ESTIMET) to compare the outcomes of 115 patients implanted with MIS under AA (MISAA group) or general anesthesia (MISGA group), or by laminectomy under general anesthesia (LGA group). All in all, awake surgery appears to show significantly better performance than general anesthesia in terms of patient pain coverage (65% vs. 34-62%), pain surface (50-76% vs. 50-61%) and pain intensity (65% vs. 35-40%), as well as improved secondary outcomes (quality of life, functional disability and depression). One step further, our results suggest that MISAA combined with intra-operative hypnosis could potentialize patient intraoperative cooperation and could be proposed as a personalized package offered to PSPS-T2 patients eligible for SCS implantation in highly dedicated neuromodulation centers.
ABSTRACT
BACKGROUND: The liquid-liquid phase separation (LLPS) of biomolecules in cell underpins the formation of membraneless organelles, which are the condensates of protein, nucleic acid, or both, and play critical roles in cellular function. Dysregulation of LLPS is implicated in a number of diseases. Although the LLPS of biomolecules has been investigated intensively in recent years, the knowledge of the prevalence and distribution of phase separation proteins (PSPs) is still lag behind. Development of computational methods to predict PSPs is therefore of great importance for comprehensive understanding of the biological function of LLPS. RESULTS: Based on the PSPs collected in LLPSDB, we developed a sequence-based prediction tool for LLPS proteins (PSPredictor), which is an attempt at general purpose of PSP prediction that does not depend on specific protein types. Our method combines the componential and sequential information during the protein embedding stage, and, adopts the machine learning algorithm for final predicting. The proposed method achieves a tenfold cross-validation accuracy of 94.71%, and outperforms previously reported PSPs prediction tools. For further applications, we built a user-friendly PSPredictor web server ( http://www.pkumdl.cn/PSPredictor ), which is accessible for prediction of potential PSPs. CONCLUSIONS: PSPredictor could identifie novel scaffold proteins for stress granules and predict PSPs candidates in the human genome for further study. For further applications, we built a user-friendly PSPredictor web server ( http://www.pkumdl.cn/PSPredictor ), which provides valuable information for potential PSPs recognition.
Subject(s)
Machine Learning , Proteins , Humans , OrganellesABSTRACT
To improve pain relief for refractory pain condition, spinal cord stimulation (SCS) needs to target the dedicated neuronal fibers within the dorsal columns. Intraoperative feedback from the patient can optimize lead placement but requires "awake surgery", allowing interaction between patient and surgeon. This can produce negative effects like anxiety and stress. To better manage these aspects, we propose to combine intraoperative hypnosis with awake anesthesia. Seventy-four patients (35 females, 22-80 years) presenting with chronic refractory pain, were offered intraoperative hypnosis during awake SCS lead implantation. Interactive conversational hypnosis was used as well as interactive touch, which was enhanced during painful moments during the lead intraoperative programming. All patients participated actively during the intraoperative testing which helped to optimize the lead positioning. They kept an extremely positive memory of the surgery and of the hypnotic experience, despite some painful moments. Pain could be reduced in these patients by using interactions and touch, which works on Gate Control modulation. Positive memory was reinforced by congratulations to create self-confidence and to induce positive expectations, which could reinforce the Diffuse Noxious Inhibitory Controls at the spinal level. Cooperation was improved because the patient was actively participating and thus, much more alert when feedback was required. Combining intraoperative hypnosis with awake anesthesia appears helpful for SCS lead implantation. It enhances patient cooperation, allows optimization of lead positioning, and leads to better pain control, positive and resourceful memory.
Subject(s)
Anesthesia , Chronic Pain , Failed Back Surgery Syndrome , Hypnosis , Pain, Intractable , Spinal Cord Stimulation , Chronic Pain/therapy , Failed Back Surgery Syndrome/therapy , Female , Humans , Spinal Cord , Treatment Outcome , WakefulnessABSTRACT
OBJECTIVES: There is a lack of clinically relevant measures for quantification of maladaptive mechanisms of the nociceptive system leading to chronic pain. Recently, we developed a method that tracks nociceptive detection thresholds (NDTs) using intraepidermal electrical stimulation. In this study, we explored the feasibility of using this NDT method in patients with persistent spinal pain syndrome type 2 (PSPS-T2) and its potential to enable observation of altered nociceptive processing induced by dorsal root ganglion (DRG) stimulation. In addition, we compared NDTs with quantitative sensory testing (QST) measurements and numeric rating scale (NRS). MATERIALS AND METHODS: A total of 12 patients with PSPS-T2 (seven men; 60.4 ± 12.3 years) experiencing chronic unilateral lower limb pain treated with DRG stimulation were included in the study. Both the NDT method and electrical and pressure QST methods were performed twice in the L5 dermatome on both the affected and the unaffected foot, once with the DRG stimulator turned off and, subsequently, once with the DRG stimulator turned on. RESULTS: The NDT method can be applied to patients with PSPS-T2. With the DRG stimulator turned off, NDTs on the affected side were significantly higher than on the unaffected side. This difference was no longer present once the DRG stimulator was turned on. Furthermore, DRG stimulation affected QST (electrical and pressure) values and NRS scores. Finally, NDTs showed larger contrasts between the sides than QST measures. CONCLUSIONS: The NDT method permitted observation of altered nociceptive function. The effect of DRG stimulation also was reflected in QST outcomes and NRS scores. The larger contrast between the sides for NDTs suggests that the NDT method might be valuable for future quantification of nociceptive dysfunction in chronic pain.
Subject(s)
Chronic Pain , Ganglia, Spinal , Chronic Pain/therapy , Electric Stimulation , Ganglia, Spinal/physiology , Humans , Male , Nociception/physiology , Pain Management/methodsABSTRACT
Nanoparticle multilayer substrates usually exhibit excellent SERS activity due to multi-dimensional plasmon coupling. However, simply increasing the layers will lead to several problems, such as complex manufacturing procedures, reduced uniformity and poor reproducibility. In this paper, the local electric field (LEF) characteristics of a Ag nanoparticle (AgNP) multilayer were systematically studied through finite element simulations. We found that, on the glass support, the LEF intensity improved with the increase in the layers of AgNPs. However, the maximum LEF could be obtained with only two layers of AgNPs on the Au film support, and it was much stronger than the optimal value of the former. To verify the simulation results, we have successfully prepared one to four layers of AgNPs on both supports with a liquid-liquid interface self-assembly method, and carried out a series of SERS measurements. The experimental results were in good agreement with the simulations. Finally, the optimized SERS substrate, the 2-AgNP@Au film, showed an ultra-high SERS sensitivity, along with an excellent signal uniformity, which had a detection ability of 1 × 10-15 M for the Rhodamine 6G (R6G) and a relative standard deviation (RSD) of 11% for the signal intensity. Our study provides important theoretical guidance and a technical basis for the optimized design and application of high-performance SERS substrates.
Subject(s)
Metal Nanoparticles , Reproducibility of Results , Spectrum Analysis, Raman/methods , SilverABSTRACT
The multidimensionality of chronic pain forces us to look beyond isolated assessment such as pain intensity, which does not consider multiple key parameters, particularly in post-operative Persistent Spinal Pain Syndrome (PSPS-T2) patients. Our ambition was to produce a novel Multi-dimensional Clinical Response Index (MCRI), including not only pain intensity but also functional capacity, anxiety-depression, quality of life and quantitative pain mapping, the objective being to achieve instantaneous assessment using machine learning techniques. Two hundred PSPS-T2 patients were enrolled in the real-life observational prospective PREDIBACK study with 12-month follow-up and received various treatments. From a multitude of questionnaires/scores, specific items were combined, as exploratory factor analyses helped to create a single composite MCRI; using pairwise correlations between measurements, it appeared to more accurately represent all pain dimensions than any previous classical score. It represented the best compromise among all existing indexes, showing the highest sensitivity/specificity related to Patient Global Impression of Change (PGIC). Novel composite indexes could help to refine pain assessment by informing the physician's perception of patient condition on the basis of objective and holistic metrics, and also by providing new insights regarding therapy efficacy/patient outcome assessments, before ultimately being adapted to other pathologies.
ABSTRACT
Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in "PREDIBACK", a multicenter observational prospective study including PSPS-T2 patients with one-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n = 136), and by pain perception for second class patients (n = 62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.
ABSTRACT
BACKGROUND: Proline specific peptidases (PSPs) are a unique group of enzymes that specifically cleave bonds formed by a proline residue. The study of PSPs is important due to their role in the maturation and degradation of peptide hormones and neuropeptides. In addition, changes in the activity of PSPs can result in pathological conditions, including various types of cancer. SCOPE OF REVIEW: PSPs annotated from the Homo sapiens genome were compared and classified by their physicochemical and biochemical features and roles in vital processes. In addition to catalytic activity, we discuss non-enzymatic functions that may regulate cellular activity. MAJOR CONCLUSIONS: PSPs apparently have multiple functions in animals. Two functions rely on the catalytic activity of the enzyme: one involved in a regulatory pathway associated with the ability of many PSPs to hydrolyze peptide hormones and neuropeptides, and the other involved in the trophic pathway associated with the proteolysis of total cellular protein or Pro-containing dietary proteins in the digestive tract. PSPs also participate in signal transduction without proteolytic activity by forming protein-protein interactions that trigger or facilitate the performance of certain functions. GENERAL SIGNIFICANCE: PSPs are underestimated as a unique component of the normal human peptidase degradome, providing the body with free proline. A comparative analysis of PSPs can guide research to develop inhibitors that counteract the abnormalities associated with changes in PSP activity, and identify natural substrates of PSPs that will enable better understanding of the mechanisms of the action of PSPs in biological processes and disease.
Subject(s)
Peptide Hydrolases/metabolism , Proline/metabolism , Amino Acid Sequence , Animals , Humans , Hydrolysis , Peptide Hydrolases/chemistry , Substrate SpecificityABSTRACT
Intensive discussions are ongoing about the interpretation of pulmonary effects observed in rats exposed to poorly soluble particles. Alveolar clearance differs between rats and humans and becomes impaired in rats at higher exposure concentrations. Some have doubted the human relevance of toxic effects observed in rats under impaired clearance conditions and have suggested that experimental exposures should stay below concentrations inducing impaired clearance. However, for regulatory purposes, insight in potential health effects at relatively high concentrations is needed to fully understand the hazard. Many aspects of impaired particle clearance remain unclear, hampering human health hazard and risk assessment. For an adequate evaluation of the impact of impaired clearance on pulmonary toxicity, a clear definition of alveolar clearance is needed that enables to quantitatively relate the level of impairment to the induction of adverse pulmonary health effects. Also, information is needed on the mechanism of action and the appropriate dose metric for the pulmonary effects observed. In absence of these data, human hazard and risk assessment can only be performed in a pragmatic way. Unless available data clearly point out otherwise, rat pulmonary toxicity including lung inflammation and tumour formation, needs to be considered relevant for human hazard and risk assessment.
Subject(s)
Air Pollutants/toxicity , Inhalation Exposure/adverse effects , Lung Injury/chemically induced , Risk Assessment/standards , Animals , Humans , Lung Injury/diagnosis , No-Observed-Adverse-Effect Level , Particle Size , Particulate Matter , Rats , Risk Assessment/methods , Species Specificity , Toxicity Tests, Chronic/methods , Toxicity Tests, Chronic/standards , Toxicity Tests, Subchronic/methods , Toxicity Tests, Subchronic/standardsABSTRACT
The objective of this work was characterize and evaluate the protein-stabilizing property of pea soluble polysaccharide (PSPS) extracted from pea by-products using spray-drying and ethanol precipitation oven drying, obtaining PSPS-A and PSPS-B, respectively. The weight average molecular weight (Mw) of PSPS-A and PSPS-B were 625â¯kDa and 809â¯kDa, respectively. The results of Fourier transform infrared spectroscopy (FT-IR) analysis indicated that PSPS-A, PSPS-B and soybean soluble polysaccharide (SSPS) contained the same functional groups. The absolute negative charges of PSPS-A or PSPS-B in aqueous solution were slightly higher than that of SSPS at pHâ¯2.0 to 7.0. The apparent diameter of PSPS-B (479.1â¯nm) was larger than that of PSPS-A (127.7â¯nm) and SSPS (209.5â¯nm) were measured by dynamic light scattering. The AFM images revealed that both PSPS-A and PSPS-B possessed star-like structures with more side chains as compared to SSPS. It was found that the addition of 0.15% PSPS-A or 0.1% PSPS-B was adequate to prevent the aggregation of protein and obtain stable dispersion. Furthermore, PSPS has a wider pH range (pHâ¯3.6-4.6) to stabilize milk protein than SSPS (pHâ¯3.6-4.2).
Subject(s)
Amylases/chemistry , Beverages/analysis , Excipients/chemistry , Food Handling/methods , Milk Proteins/chemistry , Multienzyme Complexes/chemistry , Pisum sativum/chemistry , Polysaccharides/chemistry , Animals , Carbohydrate Conformation , Dynamic Light Scattering , Excipients/isolation & purification , Hydrogen-Ion Concentration , Microscopy, Atomic Force , Molecular Weight , Particle Size , Polysaccharides/isolation & purification , Protein Aggregates , Protein Stability , Rheology , Solubility , Spectroscopy, Fourier Transform Infrared , ViscosityABSTRACT
Polysaccharopeptides (PSPs) are among the main bioactive constituents of Trametes versicolor (T. versicolor). The purpose of this research was to investigate the antioxidant activities of enzymatic hydrolysates obtained from T. versicolor polysaccharopeptides by 80 U/mL ß-1,3-glucanase (PSPs-EH80). The half-inhibitory concentration (IC50) of PSPs-EH80 in metal chelating assay, ABTS and DPPH radical scavenging test results were 0.83 mg/mL, 0.14 mg/mL and 0.52 mg/mL, respectively, which were lower than that of PSPs-EH 20 U/mL. The molecular weights of the PSPs-EH80 hydrolysates were 300, 190, 140 and 50 kDa, respectively, and the hydrolysis of polysaccharides by ß-1,3-glucanase did not change the original functional group. PSPs-EH80 reduced the reactive oxygen species (ROS) content at least twice that of treatment without PSPs-EH80. In addition, an oxidative damage test showed that PSPs-EH80 can improve HaCaT cell survival. According to our results, PSP demonstrates the potential of anti-oxidative damage; besides, enzyme hydrolysis can improve the ability of the PSP.
Subject(s)
Antioxidants , Glucan 1,3-beta-Glucosidase/chemistry , Proteoglycans , Reactive Oxygen Species/metabolism , Trametes/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Cell Line , Humans , Hydrolysis , Proteoglycans/chemistry , Proteoglycans/pharmacologyABSTRACT
Action potentials and the postsynaptic potentials they evoke fill the pages of neuroscience textbooks, but students have relatively few opportunities to record these phenomena on their own. However, the act of making such recordings can be key events in a student's scientific education. The crayfish abdominal slow flexor muscle system is a well-established platform for recording spikes and PSPs. It enables students to see nerves and the muscles they innervate, record spontaneous spikes from several motor axons in these nerves as well as PSPs in their postsynaptic muscle fibers, and interpret these recordings quantitatively. Here we describe an improved method for preparing the slow-flexor system for recording that employs transmitted illumination through the stereo microscope's conventional substage lighting. Oblique transmitted lighting allows students to see the nerve and muscles fibers in each segment clearly and position recording electrodes accurately under visual control. Because students can see the nerves, muscles, and recording electrodes, broken electrode tips are relatively uncommon and the first successful recordings come more quickly. Many kinds of neurons in the CNS have the same pattern of multineuronal, multiterminal innervation that occurs on these muscle fibers. To visualize these innervation patterns on these fibers, we describe an immunohistochemical protocol that labels the GABAergic inhibitory motor axon and all the synaptic vesicles in the synaptic terminals on these muscle fibers. Dual-color images reveal extensive branching of the axons and fields of presynaptic terminals, only some of which are double-labeled for GABA.
ABSTRACT
This article is intended to give practitioners a method to evaluate total mixed ration (TMR) consistency and to give them practical solutions to improve TMR consistency that will improve cattle performance and health. Practitioners will learn how to manage the variation in moisture and nutrients that exists in haylage and corn silage piles and in bales of hay, and methods to reduce variation in the TMR mixing and delivery process.
Subject(s)
Animal Feed , Animal Husbandry/methods , Dairying/methods , Animals , Cattle , Female , Silage , Zea maysABSTRACT
BACKGROUND: Some patients with progressive supranuclear palsy syndrome (PSPS) demonstrate a focal area of midbrain hypometabolism on FDG-PET scans which we call the 'pimple sign'. We assessed its association with midbrain atrophy, its reliability and its ability to differentiate PSPS from corticobasal syndrome (CBS) and multiple system atrophy (MSA). METHODS: We identified 67 patients with PSPS, CBS or MSA who had volumetric MRI as well as FDG-PET imaging. Midbrain volume was measured and expressed as a percentage of total intracranial volume. Two independent, blinded specialists rated the 'pimple sign' on FDG-PET as 'absent', 'possible' or 'definite'. Midbrain volumes were compared across these groups and reliability assessed with the kappa statistic. Sensitivity and specificity were calculated using CBS and MSA patients as controls. RESULTS: Midbrain volume was decreased in the 'definite' group compared to the 'absent' and 'possible' groups (p = 0.0036). Inter-rater reliability for the pimple sign was high (κ = 0.90). A 'definite pimple sign' had a high specificity (100%) but low sensitivity (29%) for PSPS, whilst the presence of a possible or definite sign had a sensitivity of 79%. CONCLUSION: The 'pimple sign' of PSPS is associated with midbrain atrophy, and may be helpful in differentiating PSPS from CBS and MSA.