Hours Of Immobilization Research Articles

Effects of Repeated Administration of Rauwolfia Serpentina on Stress-Induced Anorexia and Leptin Levels: Relationship With Adaptation to Stress

Background: Stress is a major contributor to various health issues, including depression, anorexia nervosa, diabetes, and obesity. Rauwolfia serpentina, a traditional medicinal plant, has shown potential in alleviating stress-induced effects due to its influence on serotonin neurotransmission and its anxiolytic properties. Objective: This study aimed to investigate the effects of repeated administration of Rauwolfia serpentina on stress-induced anorexia and leptin levels, and its relationship with adaptation to stress in rats. Methods: Male albino Wistar rats were divided into four groups: DMSO unstressed, DMSO stressed, Rauwolfia serpentina unstressed, and Rauwolfia serpentina stressed. The stressed groups were subjected to two hours of immobilization daily for five days, followed by oral administration of Rauwolfia serpentina at 10 mg/kg. Behavioral assessments included the open field and light-dark transition tests. Body weight, food intake, and plasma levels of glucose, leptin, and corticosterone were measured. Data were analyzed using ANOVA with post-hoc Newman-Keuls test, and significance was set at p<0.05. Results: Rauwolfia serpentina significantly improved body weight maintenance (98.9 ± 1.3% vs. 99.5 ± 1.7%) and increased food intake (16.3 ± 0.6 g vs. 16.5 ± 0.5 g) in stressed rats. It also reduced anxiety-like behaviors and lowered corticosterone levels (15.9 ± 1.6 ng/mL vs. 18.4 ± 1.7 ng/mL) in stressed groups (p<0.05). Conclusion: Rauwolfia serpentina effectively alleviates stress-induced anorexigenic and anxiogenic effects, suggesting its potential as a therapeutic agent for managing stress-related disorders.

CCN1 expression is regulated by mechanical stimuli in tendons

Tendon overuse injuries are common, but the processes that govern tendon response to mechanical load are not fully understood. A series of experiments of in vitro and in vivo experiments was devised to study to the relationship between mechanical stimuli and the matricellular protein Cellular Communication Network Factor 1 (CCN1) in tenocytes and tendons. First, human and murine tenocytes were subjected to cyclic uniaxial loading in order to evaluate changes in CCN1 gene expression as a response to mechanical stimuli. Then, baseline Ccn1 gene expression in different murine tendons (Achilles, patellar, forearm, and tail) was examined. Finally, changes in Ccn1 expression after in vivo unloading experiments were examined. It was found that CCN1 expression significantly increased in both human and murine tenocytes at 5 and 10% cyclical uniaxial strain, while 2.5% strain did not have any effect on CCN1 expression. At baseline, the Achilles, patellar, and forearm tendons had higher expression levels of Ccn1 as compared to tail tendons. Twenty-four hours of immobilization of the hind-limb resulted in a significant decrease in Ccn1 expression in both the Achilles and patellar tendons. In summary, CCN1 expression is up-regulated in tenocytes subjected to mechanical load and down-regulated by loss of mechanical load in tendons. These results show that CCN1 expression in tendons is at least partially regulated by mechanical stimuli.

Effects of short-term arm immobilization on motor skill acquisition.

Learning to sequence movements is necessary for skillful interaction with the environment. Neuroplasticity, particularly long-term potentiation (LTP), within sensorimotor networks underlies the acquisition of motor skill. Short-term immobilization of the arm, even less than 12 hours, can reduce corticospinal excitability and increase the capacity for LTP-like plasticity within the contralateral primary motor cortex. However, it is still unclear whether short-term immobilization influences motor skill acquisition. The current study aimed to evaluate the effect of short-term arm immobilization on implicit, sequence-specific motor skill acquisition using a modified Serial Reaction Time Task (SRTT). Twenty young, neurotypical adults underwent a single SRTT training session after six hours of immobilization of the non-dominant arm or an equivalent period of no immobilization. Our results demonstrated that participants improved SRTT performance overall after training, but there was no evidence of an effect of immobilization prior to task training on performance improvement. Further, improvements on the SRTT were not sequence-specific. Taken together, motor skill acquisition for sequential, individuated finger movements improved following training but the effect of six hours of immobilization was difficult to discern.

Magnetic nickel nanostructure as cellulase immobilization surface for the hydrolysis of lignocellulosic biomass

In this research, a magnetic reusable nickel nanoparticle (NiNPs) supporting materials were prepared for cellulase enzyme immobilization. The immobilized cellulase showed high activity recovery, large & fast immobilization capacity and improved pH & temperature tolerance. The excellent stability and reusability enabled the immobilized cellulase to retain 84% of its initial activity after ten cycles. At 2 mg/mL enzyme concentration, highest 93% immobilization efficiency was achieved within two hours of immobilization. When the treatment temperature reached 40 °C and pH 5, the immobilized cellulase exhibited highest residual activity. The immobilized cellulase could be separated from the solution by a magnetic force. This study introduced a novel supporting material for cellulase immobilization, and the immobilized cellulase poses a great potential in the hydrolysis of lignocellulosic biomass which can used as an easily applicable and sustainable pre-treatment step for advanced biofuel production.

Role of MP-4 myelopeptide in regulation of antibody production and functional activity of macrophages under stress conditions

Myelopeptides are endogenous low-molecular weight peptides with immunoregulatory activity. Each of these myelopeptides has an individual sequence and plays a role in correction of immune system disorders. In our earlier studies, we have shown immunomodulatory effect of MP-3, MP-5, MP-6 myelopeptides upon functioning of peritoneal macrophages under the conditions of immobilization and cold stresses. The aim of this work was to investigate the effect of MP-4 myelopeptide upon antibody formation, production of reactive oxygen species, and absorptive activity of peritoneal macrophages in mice under the immobilization stress. Materials and methods. The in vivo experiments were carried out in 24 male Swiss mice weighing 17-22 g. Two-or six-hour immobilization stress was produced in the animals. MP-4 was injected intraperitoneally 30 min before the onset of stress, at a dose of 40 μg/kg. The animals were divided into 4 groups: 1, control; 2, stress; 3, stress + MP-4; 4, MP-4 injection. On day +5, cellularity and the number of antibody-forming cells (AOC) in spleen were assessed by the method of local hemolysis in an agarose gel according to Jerne. Production of reactive oxygen species by peritoneal cells was assessed using the luminol-dependent chemiluminescence (LZHL) reaction. The absorption capacity of peritoneal macrophages was assessed using a standard method using a BDFACSCalibur laser flow cytometer. Labeled St. aureus at a final concentration of 108 cells/ml were used as phagocytosis targets. Statistical analysis was performed using the unpaired Student's t-test. Results. It was found that two-hour immobilization stress did not affect the absorption activity of peritoneal leukocytes, whereas six-hour stress suppressed phagocytosis. Injection of MP-4 in stress-exposed animals did not lead to changes in phagocytic activity of peritoneal macrophages. MP-4 did not correct the stress-induced decrease in the number of antibody-forming cells from the spleen during six hours of immobilization, nor stress-induced increase in absolute amounts of AOC under the two-hour immobilization stress. In the group of animals receiving MP-4 and immobilized for two-hours, an increase in the number of nucleated cells was increased, as compared with the control group. Thus, in contrast to the previously studied myelopeptides, MP-4 did not show pronounced immunomodulatory effects upon these parameters.

Electrodes Based on a Titanium Dioxide Nanotube-Spherical Silver Nanoparticle Composite for Sensing of Proteins.

The aim of the research was to provide electrochemical, chemical, phase, and microscopic characteristics of electrodes based on titanium dioxide nanotubes (TNTs) containing uniformly deposited, nonagglomerated spherical silver nanoparticles (AgNPs). The nanoparticles were produced with the use of electrodeposition and sputter deposition methods. This paper presents the results of research of these platforms with the use of the following techniques: electrochemical impedance spectroscopy, X-ray diffraction analysis, X-ray photoelectron spectroscopy, and scanning electron microscopy. Evaluation of the adsorption of proteins-bovine serum albumin (BSA)-was carried out to establish the possibility of the use of the electrodes in a low-cost, simple detection system without surface functionalization. The research proved that the AgNP deposition facilitated the electron transfer increasing their conductivity properties as well as promoting the protein adsorption. The AgNPs/TNT electrodes showed a high selectivity to the BSA-anti-BSA complex. Half an hour of immobilization was enough to completely saturate the TNT electrodes, whereas for AgNPs/TNTs, 1 h of immobilization seemed to be not enough. The impedance parameter changes for electrodes with the AgNPs reached even about 300%. The biggest changes were noted for the platform obtained using cyclic voltammetry, so it is the best detection platform for biosensing.

Proteomic and Phosphoproteomic Analysis of Skeletal Muscle During Hindlimb Immobilization

The maintenance of skeletal muscle mass is required for health and issues associated with the quality of life. It is known that immobilization leads to the loss of muscle mass, and a decrease in protein synthesis is one of the primary mechanisms that drive this response. Moreover, previous studies have shown that protein synthesis is largely regulated by changes in the phosphorylation state of the various factors that can control protein synthesis (e.g., initiation and elongation factors). In this study, we took advantage of the powerful capabilities of mass spectrometry (MS) to identify the proteomic and phosphoproteomic alterations that occur in response to immobilization. In total, we were able to identify and quantify alterations in 15,020 unique phosphorylation sites and 4,646 proteins. To our surprise, the rate of protein synthesis decreased within 6 hours of immobilization, but no phosphorylation sites were significantly altered at this time. At later time points (i.e., 24 and 72 hours), the rate of protein synthesis further decreased, but again this was not associated with major changes in protein phosphorylation. To verify the proteomic and phosphoproteomic results, we performed western blot analysis to assess the phosphorylation state of various proteins that have been implicated in the regulation of protein synthesis. The results from the western blot analysis were highly congruent with the MS results. Hence, when taken together, our results strongly suggest that alterations in protein phosphorylation do not play a major role in immobilization‐induced decrease in protein synthesis and muscle mass.Support or Funding InformationNational Institutes for Health grant 1R01AR057347 to T.A.H.

Evaluation of the effectiveness of immobilization of activated sludge on composite materials “polyethylene:polysaccharides”

The aim of this work is to study the immobilization ability of new composite materials based on polyethylene (PE) and polysaccharides (PS) in relation to the biocenosis of activated sludge (AS). The objects of the study were selected composite materials of the following composition: PE : pure microcellulose (MCc), PE : waste microcellulose (MCw), PE : starch (ST), at a ratio of components PE : PS = 70:30 wt.%. The objectives of the study were to determine the main morphological parameters of new composites (porosity, roughness, density), assessment of hydrochemical and hydrobiological state of AS (silt index, mass concentration of silt, species composition) until it locks into composites, assessment of the immobilization ability of the studied materials by biomass weight gain, monitoring of the state of AS after fixing. The tests found that the composite of structure of PE : MCc of has a density of 410 kg/m3 and a porosity of 60%, the roughness of 3.5; the composite of structure of PE : MCw has a density of 590 kg/m3 and a porosity of 40%, roughness of 2.0, composite of structure of PE : ST has a density of 640 kg/m3 and a porosity of 50%, the roughness of 2.5; wherein the reference sample - PE - has the parameters: density 860 kg/m3 and a porosity of 0%, roughness 0. To determine the immobilization capacity of the new composite materials, a laboratory experimental immobilizer was used, which is a container filled with 70% of the useful volume of the active sludge suspension and 30% of the floating loading samples. Immobilization was carried out under aeration conditions during 2, 4, 8, 12, 24, 48, 72 hours. As a result of tests it is established that the sample of structure of PE : MCc for 72 hours of immobilization showed a gain of biomass of the order of 12%, the sample of structure of PE : MCw - 5%, the sample of structure of PE : ST – 7%, PE – 3%. The condition of the organisms AS after fixing was evaluated by washings with immobilized samples, as a result of microscopy of washouts, the presence of living representatives of the biocenosis of AS in all samples was established, but they differ in number: for the sample of structure of PE : MCc - numerous, PE : MCw, PE : ST - average number, PE - small number. Further studies on the modification of the synthetic polyolefin matrix by functional fillers, including those from a number of polysaccharides, are of interest, allowing to increase the affinity of the carrier material with the extracellular matrix of activated sludge.

Chronic but not acute immobilization stress stably enhances hippocampal CA1 metabotropic glutamate receptor dependent Long-Term Depression

Acute stress has been shown to facilitate but not increase metabotropic glutamate receptor (mGluR) mediated Long-Term Depression (LTD) in the hippocampus. However, the effect of chronic stress on mGluR dependent LTD has not been investigated. Moreover, whether stress leads to a transient modification LTD threshold or a more stable change in synaptic plasticity needs to be addressed. In the present study, we have explored the effects of both a ten-day long and a single day immobilization stress protocol on mGluR-LTD at the CA3:CA1synapse in the hippocampus of adult male Sprague-Dawley rats, a day after applying stress. Bath application of the selective group 1 mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) promoted robust LTD in hippocampal slices from control (i.e. un-stressed) animals. Administration of immobility stress for two hours per day for ten days significantly elevated this LTD to a level almost twice that of control, when observed 24h following the last stress event. Acute stress i.e. a single day of two hours of immobilization, however, failed to significantly enhance LTD, 24h later. These results demonstrate for the first time, that repeated exposure to stress, but not a single stress event, is required to bring about a stable alteration in mGluR mediated synaptic plasticity.

Gamma absolute power reveals activation of motor areas after hand immobilization

OBJECTIVE: To analyze changes in gamma band absolute power in motor cortical areas, before and after a condition of hand immobilization for 48 hours. METHOD: Fifteen healthy volunteers, aged between 20 and 30, were submitted to EEG assessment before and after 48 hours of immobilization of the dominant hand, while performing a motor task triggered by a visual stimulus. A two-way repeated measures ANOVA with two within-group factors (moment x condition), each one with two levels (before vs. after visual stimuli; before vs. after 48-hour HI, respectively) was used to test for changes in beta band absolute power. RESULTS: Statistical analysis revealed that hand immobilization caused changes in cortical areas. A significant increase in gamma band absolute power was found after hand immobilization at electrodes F3 (p = 0.001) at F4 (p = 0.001) and at Fz (p = 0.001), at C3 (p = 0.001), C4 (p = 0.001) and Cz (p = 0.001). CONCLUSION: These results reveal that oscillations of the gamma band can be a cortical strategy to solve the effect of less activation due to movement restriction. Knowledge of the functioning of motor cortical areas after a condition of immobilization can lead to more effective strategies in rehabilitation.

Abstract 197: Selective Destruction of Adrenergic Cells in Mice Leads to Severe Left-ventricular Dysfunction at Rest With Apparent Stress-induced Recovery

The catecholamines epinephrine and norepinephrine play critical roles in the maintenance of cardiovascular function. Phenylethanolamine-N-methyltransferase (Pnmt) catalyzes the conversion of norepinephrine to epinephrine and serves as a marker for adrenergic cells. We have previously shown that the selective destruction of Pnmt+ cells in the mouse produces severe left-ventricular dysfunction under anesthesia and that epinephrine deficiency alone does not recapitulate the phenotype. Here, we test the hypothesis that Pnmt+ cells are key modulators of the stress response to immobilization. Using a suicide reporter mouse model to ablate Pnmt+ cells (Pnmt-Cre/DTA), we achieve greater than 50% Pnmt+ cell reduction in the adrenal medulla and 97% reduction in Pnmt transcript. Remarkably, Pnmt+ cell destruction does not markedly diminish the cardiovascular response to restraint stress. At one hour of immobilization, heart rate and ejection fraction showed a similar increase in response to restraint in both groups, despite apparent heart failure in Pnmt-Cre/DTA mice at rest (Figure 1). Here, we show that, while Pnmt+ cells are required for the maintenance of basal cardiovascular function, loss of these cells does not diminish the cardiovascular response to restraint stress. These results suggest that left ventricular cardiac muscle has the capacity to respond to stress despite hypokinetic and poor ventricular function at baseline.

Development of Hybrid Bio-Inorganic Catalyst for Oxygen Reduction Reaction in Enzymatic Fuel Cells

The search for alternative power sources able to generate electricity out of a fuel rather than just storing electrical current, like the battery, have turn into the development of fuel cells. Some of these fuel cells mimic the way the human body extracts energy from sugars or other organic compounds and these are called enzymatic biofuel cells (EFC). EFCs utilize enzymes to convert the chemical energy into electrical current. An important part of their design is the development of cathodes that can carry out oxygen reduction reaction (ORR) and explore the benefits of the abundant, cheap and easily available oxygen. The enzymes capable of ORR belong to the family of multi-copper oxidases, very well known in the area of EFCs. One particular enzyme, bilirubin oxidase (BOx), from that family is gaining more and more attention in the last years due to its superior performance and resistivity to halide ions. The main advantage of the enzymatic cathodes for ORR is the low overpotential of the reaction and thus the high open circuit potential (OCP) of the electrodes. At the same time, the maximum current generated from those types of cathodes is significantly lower in comparison to the traditional inorganic electrodes, which start the ORR at high overpotentials, but in contrast producing higher currents in this low potential region.In order to increase the performance of BOx cathodes for ORR, we combined the advantages of enzymatically catalyzed oxygen reduction with the advantages of ORR catalyzed by inorganic catalyst, such as non-platinum metal group catalyst (NPGM)1.Several NPGM catalysts were incorporated with BOx in ink type composite cathodes and tested using rotating disk electrode (RDE) technique in electrolyte with pH 7.5. Those catalysts were synthesized by sacrificial support method, as it was previously demonstrated1. Based on the performed screening study, two NPGM catalysts (Fe-DANM and Fe-AAPyr) demonstrated higher compatibility with the enzyme and as a result, higher performance was achieved. Fe-DANM catalyst used diaminomaleonitrile as a precursor and Fe-AAPyr proceeds from aminoantipyrine.Due to the high hydrophobicity of the NPGM catalyst, the interaction between the enzyme and the inorganic catalyst is hindered. Therefore, to provide more hydrophilic environment and enhance the enzyme immobilization, carbon nanotubes were introduced in the NPGM-BOx composite along with 1-pyrenebutanoic acid succinimidyl ester (PBSE) as a tethering agent. The ink composition was optimized in terms of: (1) NPGM:CNTs ratio, (2) amount of enzyme, (3) linker and (4) time of immobilization, showing that 1:1 NPGM:CNTs ratio with 10 mg/ml BOx, 10 mM PBSE and 16-18 hours of immobilization is the optimum ink formula.The aim of these NPGM-CNTs-BOx composites was to increase the cathodes final output in the broad potential region, combining the pronounced advantages of the enzymatic catalysis at high potentials and the ones of the inorganic catalysis at low potentials. Figure 1 clearly demonstrates that the simultaneous utilization of bio- and inorganic catalysis leads to improvement of the generated current densities in the whole range of potentials tested.After the positive effect of the combined NPGM-CNTs-BOx catalyst was demonstrated, a step forward was taken to improve the NPGM-CNTs interactions. NPGM catalyst (Fe-AAPyr) was in situ synthesized on multi-walled carbon nanotubes creating “fused” NPGM-CNTs composite. This composite was used for the development of the catalytic layer (CL) of gas-diffusion “hybrid” cathode. The gas-diffusion layer (GDL) of this cathode consisted on teflonized carbon black, on which the CL was pressed. BOx was physically adsorbed on the NPGM-CNTs “fused” catalyst and the performance of the cathodes was studied by polarization measurements (Fig.2). The comparison of the output of two identical cathodes differing in the preparation of the NPGM-CNTs composition shows the benefits of the in situ preparation technique.The introduction of NPGM catalysts into biological electrochemical systems, such as an enzymatic electrode for ORR, showed a notable improvement of the cathode’s performance, proving the described herein principal. This opens the venue for new applications of enzymatic biofuel cell, from biosensors to energy production.[1] Brocato, S., A. Serov, P. Atanassov Electrochimica Acta 2013, 87, 361– 365[2] Brocato, S., C. Lau, P. Atanassov Electrochimica Acta 2012, 61, 44– 49

Hematological Parameters and Redox Balance of Rat Blood in the Dynamics of Immobilization

Hematological and biochemical parameters were studied in rat blood in the dynamics of immobilization (0.5, 1, and 3 h). Immobilization was followed by a release of old erythrocytes in the circulation and the development of reticulocytosis. The neutrophil count significantly increased by the third hour of immobilization. Restraint stress induced changes in activities of antioxidant enzymes (SOD and catalase) in erythrocytes and plasma level of MDA. The correlation between each enzyme (SOD, glutathione peroxidase, and catalase) and MDA concentration was the highest 1 h after the beginning of immobilization. These data can reflect the tension of antioxidant systems in red blood cells. The biochemical parameters returned to the basal level by the third hour of immobilization. Correlation coefficients between the activities of antioxidant enzymes and MDA amount decreased after 3 h of stress and the correlation between glutathione peroxidase and reduced glutathione significantly increased. The redox status of the blood returned to the initial values after 3 h.

Venous Thromboembolism (VTE) in Patients (pts.) with Monoclonal Gammopathy of Undetermined Significance (MGUS)

Introduction: MGUS is considered to be a pre-malignant condition, and previous studies have reported VTE as a marker for a subsequent malignancy. We conducted a retrospective study to evaluate the incidence of VTE among MGUS patients (pts) and to correlate this incidence with different risk groups for developing malignancy in MGUS pts.Methods: The complete medical records of all MGUS pts at Cleveland Clinic Cancer Center at Fairview hospital from Jun/2005–Jun/2008 were retrospectively reviewed. Of 237 pts diagnosed with MGUS, 112 pts (65 males, 47 females) were eligible for our study. These pts were divided into 2 risk groups: low risk (LR)/low-intermediate risk (LIR) group (78 pts.) and high intermediate risk (HIR)/high risk (HR) group (34 pts) based on the Risk Stratification Model using three adverse risk factors; serum M-protein level ≥ 3 gm/dL, non-IgG MGUS, and an abnormal kappa/lambda free light chain ratio. Only pts with ≥ 12 months follow up were included. Exclusion criteria included a personal history of inherited thrombophilia, previous episode of VTE or anticoagulant treatment, thrombocytosis, malignancy, and renal impairment. Risk factors (RF) for VTE were identified in each pt and categorized into four groups: no RF, 0; one RF, 1; two RF, 2; and > 2 RF, >2. RF included > 48 hours of immobilization, surgery in the past 3 months, current hospitalization at the time of VTE occurrence, oral contraceptive use, and congestive heart failure.Objectives:To compare the proportion of pts with MGUS who developed VTE to the proportion of pts in the general population who developed VTE.To compare VTE incidence between the two risk groups.Results: During the study period, 9 pts with MGUS experienced VTE. In the general population, the incidence of VTE is 117/100,000 persons/year (from literature). Therefore, the proportion of pts in the general population over 3 years was 117/100000 × 3 =0.0035. The proportion of VTE in MGUS pts, adjusted for 3 years, of 0.080 is significantly higher than that for the general population (p<0.001). Comparison of VTE incidence between the two risk groups, while adjusting for the number of risk factors, showed no difference (Cox Proportional Model, p=0.38). There is no significant difference in the risk of VTE among different levels of risk factors (p=0.96). The Kaplan-Meier estimates of the proportions of pts free of VTE at 24 months are 0.96 and 0.93 for the LR/LIR and HIR/HR groups, respectively.Conclusions: MGUS is associated with a significantly higher rate of VTE compared to the general population. Despite many studies indicating VTE as a marker for subsequent malignancy, we did not find a difference in the incidence of VTE among the various risk factor groups. Any suggestive signs of VTE in pts with MGUS should be promptly evaluated and treatment initiated as soon as possible. Since the number of pts is small and the period of follow-up relatively short, a prospective cohort study is needed to verify our results.Table?: Comparison of event rate:VTEPop-valueTotal number of ptsRisk stratification model (pts)Groups (pts)VTE Proportion112LR (38)LR/LIR (78)(5)LIR (40)0.0800.0035<0.001HIR (26)HIR/HR (34)(4)HR (8)Note: Po is the VTE proportion for the general population over a 3-year time period.

How chronic stress exacerbates cancer

Having cancer is stressful enough without the knowledge that stress itself promotes tumor growth. But Premal Thaker, Liz Han, Aparna Kamat, Anil Sood (University of Texas M.D. Anderson Cancer Center, Houston, TX), and colleagues have found just that: human ovarian carcinoma cells injected into mice form tumors that grow more when the mice are exposed to chronic stress. Drugs that block stress responses may therefore be appropriate for certain cancer patients. Figure 1 Stress-dependent increases in vessel density (top, left to right) and tumor weight and number (bottom) are prevented by VEGF antagonist PTK787. Humans and mice have two major responses to stress. The adrenal gland responds by producing glucocorticoids, and the sympathetic nervous system by producing catecholamines, which bind to the β adrenergic receptors ADRB1 and ADRB2. The Texan group identified a pathway leading from ADRB2 to protein kinase A (PKA) and the production of VEGF. VEGF is known to induce angiogenesis (the growth of new blood vessels) and thus to aid tumor growth. The group had earlier found that patients with greater distress had higher levels of VEGF, and that catecholamines but not glucocorticoids were clearly linked in vitro to increased production of VEGF by cancer cells. In the current study with the injected mice, they found that social isolation, 2 hours of immobilization daily, or a β2 agonist caused tumor nodule number and mean tumor weight to approximately double or triple. Levels of VEGF and mean vessel density in the tumors were both increased. All of these stress-mediated increases were blocked by reducing the levels of ADRB2 (but not ADRB1) or by antagonizing PKA or VEGF. Only tumors that express ADRB2 will be susceptible to this particular stress pathway. It is not clear how large this universe is, as there have not been large-scale surveys of ADRB2 expression in different tumor types. Patients with tumors that express high levels of ADRB2, and who have significant stressors such as surgery or lack of social support, would be the best candidates for a trial of β blockers as potential cancer therapeutics. These adrenergic receptor antagonists are widely used for hypertension, but may find a new application in reducing the negative effects of stress on tumor growth. Reference: Thaker, P.H., et al. 2006. Nat. Med. doi:.10.1038/nm1447 [PubMed] [Cross Ref]

Effects of immobilization and dynamic compression on intervertebral disc cell gene expression in vivo.

An in vivo analysis of the intervertebral disc's cellular response to dynamic compression and immobilization was performed using a rat-tail model. To assess the effects of immobilization and short-term dynamic compression on intervertebral disc cell expression of anabolic and catabolic genes. Static compressive loads applied in vivo alter the composition of the disc matrix and cell viability in a dose-dependent manner. The effects of in vivo dynamic compression, which is a more physiologic load, and reported risk factor for low back pain have not been investigated. An Ilizarov-type device was implanted on the rat tail and used to determine the effects from 72 hours of immobilization (n = 6), 2 hours of dynamic compression (1 MPa/0.2 Hz) (n = 8), and the coupled effect of immobilization followed by compression (n = 8). Real-time reverse transcription-polymerase chain reaction was used to measure changes in anabolic and catabolic gene levels relative to both internal control subjects and a sham-operated group (n = 7). Immobilization and dynamic compression affect anabolic and catabolic genes, with an overall downregulation of types 1 and 2 collagen and upregulation of aggrecanase, collagenase, and stromelysin in the anulus. The effects of immobilization and compression appear to be additive for collagen types 1 and 2 in the anulus, but not in the nucleus, and not for catabolic genes. Short-duration dynamic compression and immobilization alter gene expression in the rat disc. In studying the response of the disc to loading, it is necessary to look at both anabolic and catabolic pathways, and to consider strain history.

Body weight gain and diurnal differences of corticosterone changes in response to acute and chronic stress in rats

Plasmatic levels of corticosterone display a circadian rhythm, with the higher values occurring during the dark phase in nocturnally feeding animals. Stressful situations induce a rise of corticosterone levels and this endocrine response to stress also presents circadian variations. The higher increase of corticosterone in response to stress occurs when the hormone is in its lower circadian level, and the minimum responses occurring at the peak. Since it has been shown that plasma hormones respond differently to different stressors, in the present study, we compared the acute and chronic effects of four different stressors: electric foot shocks (3 mA, 1/s, 5 min), immobilization during two hours or six hours, and immersion in cold water (15°C) for 15 min. Stressors were applied, both acutely and chronically (during 4, 12 and 20 days) at the onset of the light phase as well as at the onset of the dark phase of the light/dark cycle. Body weight was assessed every day, and at the end of the manipulations plasmatic corticosterone levels were determined from the trunk blood. Adrenal and testicular weights were also assessed. Acute exposure to stressors increased plasmatic corticosterone levels significantly when the stressors were applied at the beginning of the light phase of the cycle. In the dark phase, only two hours of immobilization and immersion in cold water caused an increase in plasmatic corticosterone. With repeated exposure, electric foot shocks failed to induce significant changes in corticosterone levels in any phase of the light–dark cycle. Immobilization stress induced a significant rise in corticosterone levels only when the stressor was applied during the light phase. Immersion in cold water elicited a clear increase in plasmatic corticosterone levels in all the periods tested, regardless of the time of the cycle in which the stressor was applied. We did not observe a loss in body weight, but rather a smaller weight gain in stressed rats. Body weight gain was minimum in rats exposed to immersion and 6 hours of immobilization. Adrenal hypertrophy was observed in rats exposed to these same stressors. We conclude that: 1) the activation of the hypothalamus-pituitary-adrenal axis by stress depends mainly on the characteristics of the stressor; 2) the response of this axis to stress also depends on the time of day in which the stressor is applied.

Single bout of exercise eliminates the immobilization-induced oxidative stress in rat brain

We were interested in the effects of immobilization (IM), a single bout of exercise (E) and immobilization followed by exercise (EIM) on memory and oxidative damage of macromolecules in hippocampus of rat brain. Eight hours of IM resulted in impairment of passive avoidance test (memory retrieval deficit) and increased latency to start locomotion in an open-field test. Two hours of swimming did not significantly alter the memory retrieval deficit and latency, while the EIM group had longer latency and similar memory than control and E groups. The oxidative damage of lipids, proteins and nuclear DNA increased significantly in IM group and no increase was observed in E and EIM animals. The activity of proteasome was not altered in any groups. The activity of glutamine synthetase (GS) was decreased in IM group ( P<0.05), this down regulation was not observed in E and EIM groups. These data suggest that oxidative damage of macromolecules is associated with impaired cognitive function. Single bout of exercise after immobilization eliminates the oxidative damage of macromolecules and normalizes memory function, probably by its ability to restore the activity level of GS and eliminate the consequences of immobilization-induced prolonged efflux of glutamate.

Abnormal mitochondria and sarcoplasmic changes in rabbit skeletal muscle induced by immobilization.

Immobilization of the rabbit knee in extended position results in damage to the vastus intermedius profundus (VIP) muscle. To examine the mechanisms involved in initiation of the injury, we studied the light and electron microscopic morphology of the VIP muscle, as well as the activity and distribution of NADH tetrazolium reductase (NADH-TR) in the affected muscle, and determined serum total creatine kinase (CK) activity in immobilized rabbits. The VIP muscle of the immobilized right hindlimb was removed at various time points (10 h, 24 h, 36 h and 48-72 h, n=5 for each time point). The nonimmobilized left hindlimb and five nonimmobilized animals served as controls. No morphological changes were observed by light microscopy within 48-72 h in routine stainings. Transient ultrastructural abnormalities, including abnormal cristae, matrix lucencies and mild swelling of mitochondria, were observed between 10 h and 36 h of immobilization, subsiding by 48-72 h. On the other hand, progressive disorganization of myofibrils with breaking-up of Z-bands and an increase in the number and size of sarcoplasmic lipid vacuoles was seen with increasing duration of immobilization. NADH-TR activity at subsarcolemmal locations had decreased by 10 h and disappeared by 24 h of immobilization, while the intermyofibrillar mitochondria remained unaltered. Serum total CK activity began to increase by 2 h of immobilization and reached a peak by 24 h. The results indicate that already a few hours of immobilization of the rabbit knee in extension leads to signs of metabolic disturbance of the VIP muscle and sarcolemmal leakage. The simultaneous occurrence of transient mitochondrial abnormalities, transient CK efflux and progressive myofibrillar damage suggests the operation of multiple adverse mechanisms already at the onset of disuse muscle atrophy.

Treatment of Winery Wastewater In A Reactive PU‐Immobilized Anaerobic Fluidized Bed Reactor

AbstractImmobilization of methanogens through direct reactive polymerization of TDI (tolylene diisocyanate) and PPG (polypropylene glycol) was shown to be successful. Rapid and early startup occurred within 48 hours of immobilization, with methane production rate 12.6 L/L‐day. In treating synthetic wastewater (SW), maximum percent sugar and COD eliminations at influent sugar loadings 4 g/L and 2 g/L were found to be 98.5% and 91.3 % respectively at hydraulic retention time (HRT) of 250 min. Whereas in treating winery wastewater (WW) at the same HRT, the treatment efficiency for sugar; protein; and COD was 94.1%; 90.3%; and 84.25%, respectively. While the methane production rate reached 8.75 L/L‐day. The features of direct reactive polyurethane(PU) ‐immobilization can be considered to be feasible as a new process innovation.