Improved assessment of outcomes following transient global cerebral ischemia in mice

DEFF Research Database (Denmark)

Spray, Stine; Edvinsson, Lars

2016-01-01

by limited neurological assessment protocols and present insufficient reporting of the cumulative survival rate. Therefore, we aim at developing a reproducible and easily implementable model of transient GCI in mice with minimal impact on normal mouse behavior. GCI was induced in male C57BL/6 mice......Mouse models of global cerebral ischemia (GCI) allow experimental examination of cerebral pathophysiology in genetically modified mice and fast screening of new treatment strategies. Various surgical protocols of GCI-induction in mice have been published; however, many of these studies are hindered...... and again daily for up to 7 days after GCI or sham operation and was found to be significantly decreased 1-7 days after GCI compared to sham. Furthermore, we found delayed neuronal cell death in the frontal cortex and hippocampus 5 and 7 days after GCI but not at day 3 or after sham operation. The survival...

Pharmacologic Treatment Assigned for Niemann Pick Type C1 Disease Partly Changes Behavioral Traits in Wild-Type Mice.

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Schlegel, Victoria; Thieme, Markus; Holzmann, Carsten; Witt, Martin; Grittner, Ulrike; Rolfs, Arndt; Wree, Andreas

2016-11-09

Niemann-Pick Type C1 (NPC1) is an autosomal recessive inherited disorder characterized by accumulation of cholesterol and glycosphingolipids. Previously, we demonstrated that BALB/c-npc1 nih Npc1 -/- mice treated with miglustat, cyclodextrin and allopregnanolone generally performed better than untreated Npc1 -/- animals. Unexpectedly, they also seemed to accomplish motor tests better than their sham-treated wild-type littermates. However, combination-treated mutant mice displayed worse cognition performance compared to sham-treated ones. To evaluate effects of these drugs in healthy BALB/c mice, we here analyzed pharmacologic effects on motor and cognitive behavior of wild-type mice. For combination treatment mice were injected with allopregnanolone/cyclodextrin weekly, starting at P7. Miglustat injections were performed daily from P10 till P23. Starting at P23, miglustat was embedded in the chow. Other mice were treated with miglustat only, or sham-treated. The battery of behavioral tests consisted of accelerod, Morris water maze, elevated plus maze, open field and hot-plate tests. Motor capabilities and spontaneous motor behavior were unaltered in both drug-treated groups. Miglustat-treated wild-type mice displayed impaired spatial learning compared to sham- and combination-treated mice. Both combination- and miglustat-treated mice showed enhanced anxiety in the elevated plus maze compared to sham-treated mice. Additionally, combination treatment as well as miglustat alone significantly reduced brain weight, whereas only combination treatment reduced body weight significantly. Our results suggest that allopregnanolone/cyclodextrin ameliorate most side effects of miglustat in wild-type mice.

Pharmacologic Treatment Assigned for Niemann Pick Type C1 Disease Partly Changes Behavioral Traits in Wild-Type Mice

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Victoria Schlegel

2016-11-01

Full Text Available Niemann-Pick Type C1 (NPC1 is an autosomal recessive inherited disorder characterized by accumulation of cholesterol and glycosphingolipids. Previously, we demonstrated that BALB/c-npc1nihNpc1−/− mice treated with miglustat, cyclodextrin and allopregnanolone generally performed better than untreated Npc1−/− animals. Unexpectedly, they also seemed to accomplish motor tests better than their sham-treated wild-type littermates. However, combination-treated mutant mice displayed worse cognition performance compared to sham-treated ones. To evaluate effects of these drugs in healthy BALB/c mice, we here analyzed pharmacologic effects on motor and cognitive behavior of wild-type mice. For combination treatment mice were injected with allopregnanolone/cyclodextrin weekly, starting at P7. Miglustat injections were performed daily from P10 till P23. Starting at P23, miglustat was embedded in the chow. Other mice were treated with miglustat only, or sham-treated. The battery of behavioral tests consisted of accelerod, Morris water maze, elevated plus maze, open field and hot-plate tests. Motor capabilities and spontaneous motor behavior were unaltered in both drug-treated groups. Miglustat-treated wild-type mice displayed impaired spatial learning compared to sham- and combination-treated mice. Both combination- and miglustat-treated mice showed enhanced anxiety in the elevated plus maze compared to sham-treated mice. Additionally, combination treatment as well as miglustat alone significantly reduced brain weight, whereas only combination treatment reduced body weight significantly. Our results suggest that allopregnanolone/cyclodextrin ameliorate most side effects of miglustat in wild-type mice.

Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice

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Andrés-Hernando, Ana; Altmann, Christopher; Ahuja, Nilesh; Lanaspa, Miguel A.; Nemenoff, Raphael; He, Zhibin; Ishimoto, Takuji; Simpson, Pete A.; Weiser-Evans, Mary C.; Bacalja, Jasna

2011-01-01

Patients with acute kidney injury (AKI) have increased serum proinflammatory cytokines and an increased occurrence of respiratory complications. The aim of the present study was to examine the effect of renal and extrarenal cytokine production on AKI-mediated lung injury in mice. C57Bl/6 mice underwent sham surgery, splenectomy, ischemic AKI, or ischemic AKI with splenectomy and kidney, spleen, and liver cytokine mRNA, serum cytokines, and lung injury were examined. The proinflammatory cytokines IL-6, CXCL1, IL-1β, and TNF-α were increased in the kidney, spleen, and liver within 6 h of ischemic AKI. Since splenic proinflammatory cytokines were increased, we hypothesized that splenectomy would protect against AKI-mediated lung injury. On the contrary, splenectomy with AKI resulted in increased serum IL-6 and worse lung injury as judged by increased lung capillary leak, higher lung myeloperoxidase activity, and higher lung CXCL1 vs. AKI alone. Splenectomy itself was not associated with increased serum IL-6 or lung injury vs. sham. To investigate the mechanism of the increased proinflammatory response, splenic production of the anti-inflammatory cytokine IL-10 was determined and was markedly upregulated. To confirm that splenic IL-10 downregulates the proinflammatory response of AKI, IL-10 was administered to splenectomized mice with AKI, which reduced serum IL-6 and improved lung injury. Our data demonstrate that AKI in the absence of a counter anti-inflammatory response by splenic IL-10 production results in an exuberant proinflammatory response and lung injury. PMID:21677145

Short and long-term effects of sham-controlled prefrontal EEG-neurofeedback training in healthy subjects.

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Engelbregt, H J; Keeser, D; van Eijk, L; Suiker, E M; Eichhorn, D; Karch, S; Deijen, J B; Pogarell, O

2016-04-01

In this study we evaluated long-term effects of frontal beta EEG-neurofeedback training (E-NFT) on healthy subjects. We hypothesized that E-NFT can change frontal beta activity in the long-term and that changes in frontal beta EEG activity are accompanied by altered cognitive performance. 25 healthy subjects were included and randomly assigned to active or sham E-NFT. On average the subjects underwent 15 E-NFT training sessions with a training duration of 45 min. Resting-state EEG was recorded prior to E-NFT training (t1) and in a 3-year follow-up (t3). Compared to sham E-NFT, which was used for the control group, real E-NFT increased beta activity in a predictable way. This increase was maintained over a period of three years post training. However, E-NFT did not result in significantly improved cognitive performance. Based on our results, we conclude that EEG-NFT can selectively modify EEG beta activity both in short and long-term. This is a sham controlled EEG neurofeedback study demonstrating long-term effects in resting state EEG. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Randomized sham-controlled trial of renal sympathetic denervation in mild resistant hypertension.

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Desch, Steffen; Okon, Thomas; Heinemann, Diana; Kulle, Konrad; Röhnert, Karoline; Sonnabend, Melanie; Petzold, Martin; Müller, Ulrike; Schuler, Gerhard; Eitel, Ingo; Thiele, Holger; Lurz, Philipp

2015-06-01

Few data are available with regard to the effectiveness of renal sympathetic denervation in patients with resistant hypertension yet only mildly elevated blood pressure (BP). Patients with resistant hypertension and slightly elevated BP (day-time systolic pressure, 135-149 and diastolic pressure, 90-94 mm Hg on 24-hour ambulatory measurement) were randomized in a 1:1 ratio to renal sympathetic denervation with the Symplicity Flex Catheter (Medtronic) or an invasive sham procedure. The primary efficacy end point was the change in 24-hour systolic BP at 6 months between groups in the intention to treat population. A total of 71 patients underwent randomization. Baseline day-time systolic BP was 144.4±4.8 mm Hg in patients assigned to denervation and 143.0±4.7 mm Hg in patients randomized to the sham procedure. The mean change in 24-hour systolic BP in the intention to treat cohort at 6 months was -7.0 mm Hg (95% confidence interval, -10.8 to -3.2) for patients undergoing denervation and -3.5 mm Hg (95% confidence interval, -6.7 to -0.2) in the sham group (P=0.15). In the per protocol population, the change in 24-hour systolic BP at 6 months was -8.3 mm Hg (95% confidence interval, -11.7 to -5.0) for patients undergoing denervation and -3.5 mm Hg (95% confidence interval, -6.8 to -0.2) in the sham group (P=0.042). In patients with mild resistant hypertension, renal sympathetic denervation failed to show a significant reduction in the primary end point of 24-hour systolic BP at 6 months between groups in the intention to treat analysis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01656096. © 2015 American Heart Association, Inc.

Altered left ventricular performance in aging physically active mice with an ankle sprain injury.

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Turner, Michael J; Guderian, Sophie; Wikstrom, Erik A; Huot, Joshua R; Peck, Bailey D; Arthur, Susan T; Marino, Joseph S; Hubbard-Turner, Tricia

2016-02-01

We assessed the impact of differing physical activity levels throughout the lifespan, using a musculoskeletal injury model, on the age-related changes in left ventricular (LV) parameters in active mice. Forty male mice (CBA/J) were randomly placed into one of three running wheel groups (transected CFL group, transected ATFL/CFL group, SHAM group) or a SHAM Sedentary group (SHAMSED). Before surgery and every 6 weeks after surgery, LV parameters were measured under 2.5 % isoflurane inhalation. Group effects for daily distance run was significantly greater for the SHAM and lesser for the ATLF/CFL mice (p = 0.013) with distance run decreasing with age for all mice (p age, interaction (group × age) was noted with LV posterior wall thickness-to-radius ratios (h/r) where h/r increased with age in the ATFL/CFL and SHAMSED mice while the SHAM and CFL mice exhibited decreased h/r with age (p = 0.0002). Passive filling velocity (E wave) was significantly greater in the SHAM mice and lowest for the ATFL/CFL and SHAMSED mice (p age. Active filling velocity (A wave) was not different between groups (p = 0.10). Passive-to-active filling velocity ratio (E/A ratio) was different between groups (p activity beginning at 9 months of age. Passive-to-active filling velocity ratio decreased with age (p activity throughout the lifespan improved LV structure, passive filling velocity, and E/A ratio by 6 to 9 months of age and attenuated any negative alterations throughout the second half of life. The diastolic filling differences were found to be significantly related to the amount of activity performed by 9 months and at the end of the lifespan.

Testosterone Modifies Alterations to Detrusor Muscle after Partial Bladder Outlet Obstruction in Juvenile Mice

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Andrew S. Flum

2017-06-01

Full Text Available Lower urinary tract symptoms secondary to posterior urethral valves (PUV arise in boys during adolescence. The reasons for this have previously been attributed to increased urine output as boys experience increased growth. Additionally, there are few choices for clinicians to effectively treat these complications. We formed the new hypothesis that increased androgen levels at this time of childhood development could play a role at the cellular level in obstructed bladders. To test this hypothesis, we investigated the role of testosterone on bladder detrusor muscle following injury from partial bladder outlet obstruction (PO in mice. A PO model was surgically created in juvenile male mice. A group of mice were castrated by bilateral orchiectomy at time of obstruction (CPO. Testosterone cypionate was administered to a group of castrated, obstructed mice (CPOT. Bladder function was assessed by voiding stain on paper (VSOP. Bladders were analyzed at 7 and 28 days by weight and histology. Detrusor collagen to smooth muscle ratio (Col/SM was calculated using Masson’s trichrome stain. All obstructed groups had lower max voided volumes (MVV than sham mice at 1 day. Hormonally intact mice (PO continued to have lower MVV at 7 and 28 days while CPO mice improved to sham levels at both time points. In accordance, PO mice had higher bladder-to-body weight ratios than CPO and sham mice demonstrating greater bladder hypertrophy. Histologically, Col/SM was lower in sham and CPO mice. When testosterone was restored in CPOT mice, MVV remained low at 7 and 28 days compared to CPO and bladder-to-body weight ratios were also greater than CPO. Histologic changes were also seen in CPOT mice with higher Col/SM than sham and CPO mice. In conclusion, our findings support a role for testosterone in the fibrotic changes that occur after obstruction in male mice. This suggests that while other changes may occur in adolescent boys that cause complication in boys

Cardiac autonomic modulation by estrogen in female mice undergoing ambulatory monitoring and in vivo electrophysiologic testing.

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Saba, Samir; Shusterman, Vladimir; Usiene, Irmute; London, Barry

2004-04-01

Estrogen is an important modulator of cardiovascular risk, but its mechanism of action is not fully understood. We investigated the effect of ovariectomy and its timing on the cardiac electrophysiology in mice. Thirty female mice (age 18.8 +/- 3.1 weeks) underwent in vivo electrophysiologic testing before and after autonomic blockade. Fifteen mice were ovariectomized prepuberty (PRE) and ten postpuberty (POST), 2 weeks prior to electrophysiologic testing. Five age-matched sham-operated female mice (Control) served as controls. A subset of 13 mice (5 PRE, 3 POST, and 5 Controls) underwent 24-hour ambulatory monitoring. With ambulatory monitoring, the average (668 +/- 28 vs 769 +/- 52 b/min, P = 0.008) and minimum (485 +/- 47 vs 587 +/- 53 b/min, P = 0.02) heart rates were significantly slower in the ovariectomized mice (PRE and POST groups) compared to the Control group. At baseline electrophysiologic testing, there were no significant differences among the ovariectomized and intact mice in any of the measured parameters. With autonomic blockade, the Control group had a significantly larger change (delta) in the atrioventricular (AV) nodal Wenckebach (AVW) periodicity (deltaAVW = 11.3 +/- 2.9 vs 2.1 +/- 7.3 ms, P = 0.05) and functional refractory period (deltaFRP = 11.3 +/- 2.1 vs 1.25 +/- 6.8 ms, P = 0.02) compared to the ovariectomized mice. These results were not altered by the time of ovariectomy (PRE vs POST groups). Our results suggest that estrogen modulates the autonomic inputs into the murine sinus and AV nodes. These findings, if replicated in humans, might underlie the observed clustering of certain arrhythmias around menstruation and explain the higher incidence of arrhythmias in men and postmenopausal women.

Single-particle properties from Kohn-Sham Green's functions

International Nuclear Information System (INIS)

Bhattacharyya, Anirban; Furnstahl, R.J.

2005-01-01

An effective action approach to Kohn-Sham density functional theory is used to illustrate how the exact Green's function can be calculated in terms of the Kohn-Sham Green's function. An example based on Skyrme energy functionals shows that single-particle Kohn-Sham spectra can be improved by adding sources used to construct the energy functional

Deep cerebellar nuclei play an important role in two-tone discrimination on delay eyeblink conditioning in C57BL/6 mice.

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Toshiro Sakamoto

Full Text Available Previous studies have shown that deep cerebellar nuclei (DCN-lesioned mice develop conditioned responses (CR on delay eyeblink conditioning when a salient tone conditioned stimulus (CS is used, which suggests that the cerebellum potentially plays a role in more complicated cognitive functions. In the present study, we examined the role of DCN in tone frequency discrimination in the delay eyeblink-conditioning paradigm. In the first experiment, DCN-lesioned and sham-operated mice were subjected to standard simple eyeblink conditioning under low-frequency tone CS (LCS: 1 kHz, 80 dB or high-frequency tone CS (HCS: 10 kHz, 70 dB conditions. DCN-lesioned mice developed CR in both CS conditions as well as sham-operated mice. In the second experiment, DCN-lesioned and sham-operated mice were subjected to two-tone discrimination tasks, with LCS+ (or HCS+ paired with unconditioned stimulus (US, and HCS- (or LCS- without US. CR% in sham-operated mice increased in LCS+ (or HCS+ trials, regardless of tone frequency of CS, but not in HCS- (or LCS- trials. The results indicate that sham-operated mice can discriminate between LCS+ and HCS- (or HCS+ and LCS-. In contrast, DCN-lesioned mice showed high CR% in not only LCS+ (or HCS+ trials but also HCS- (or LCS- trials. The results indicate that DCN lesions impair the discrimination between tone frequency in eyeblink conditioning. Our results suggest that the cerebellum plays a pivotal role in the discrimination of tone frequency.

The Effect of Low Calcium Diet on Bone in Ovariectomized Mice

OpenAIRE

Minematsu, Akira; Yoshimura, Osamu; Yotsuji, Hirofumi; Ichigo, Hirozo; Takayanagi, Kiyomi; Kobayashi, Ryuji; Hosoda, Masataka; Sasaki, Hisato; Maejima, Hiroshi; Matsuda, Yuichi; Tanaka, Sachiko; Kanemura, Naohiko; Matsuo, Akihisa

2000-01-01

This study investigates the effects of Ca on bone in the ovariectomized mice. Twenty-six female ICR mice aged 5 weeks were used. They were ovariectomized (OVX) or sham-operated (SHAM) and fed standard mouse diet (SF) or special low calcium diet (L.Ca), respectively. All animals were sacrificed at day 100 after operation. Mechanical strength of the left femur and tibia was measured by the three-point bending strength test. The bones were dried, weighed and burned to ash. Correlation between me...

High-frequency, low-magnitude vibration does not prevent bone loss resulting from muscle disuse in mice following botulinum toxin injection.

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Manske, Sarah L; Good, Craig A; Zernicke, Ronald F; Boyd, Steven K

2012-01-01

High-frequency, low-magnitude vibration enhances bone formation ostensibly by mimicking normal postural muscle activity. We tested this hypothesis by examining whether daily exposure to low-magnitude vibration (VIB) would maintain bone in a muscle disuse model with botulinum toxin type A (BTX). Female 16-18 wk old BALB/c mice (N = 36) were assigned to BTX-VIB, BTX-SHAM, VIB, or SHAM. BTX mice were injected with BTX (20 µL; 1 U/100 g body mass) into the left hindlimb posterior musculature. All mice were anaesthetized for 20 min/d, 5 d/wk, for 3 wk, and the left leg mounted to a holder. Through the holder, VIB mice received 45 Hz, ± 0.6 g sinusoidal acceleration without weight bearing. SHAM mice received no vibration. At baseline and 3 wk, muscle cross-sectional area (MCSA) and tibial bone properties (epiphysis, metaphysis and diaphysis) were assessed by in vivo micro-CT. Bone volume fraction in the metaphysis decreased 12 ± 9% and 7 ± 6% in BTX-VIB and BTX-SHAM, but increased in the VIB and SHAM. There were no differences in dynamic histomorphometry outcomes between BTX-VIB and BTX nor between VIB and SHAM. Thus, vibration did not prevent bone loss induced by a rapid decline in muscle activity nor produce an anabolic effect in normal mice. The daily loading duration was shorter than would be expected from postural muscle activity, and may have been insufficient to prevent bone loss. Based on the approach used in this study, vibration does not prevent bone loss in the absence of muscle activity induced by BTX.

High-frequency, low-magnitude vibration does not prevent bone loss resulting from muscle disuse in mice following botulinum toxin injection.

Directory of Open Access Journals (Sweden)

Sarah L Manske

Full Text Available High-frequency, low-magnitude vibration enhances bone formation ostensibly by mimicking normal postural muscle activity. We tested this hypothesis by examining whether daily exposure to low-magnitude vibration (VIB would maintain bone in a muscle disuse model with botulinum toxin type A (BTX. Female 16-18 wk old BALB/c mice (N = 36 were assigned to BTX-VIB, BTX-SHAM, VIB, or SHAM. BTX mice were injected with BTX (20 µL; 1 U/100 g body mass into the left hindlimb posterior musculature. All mice were anaesthetized for 20 min/d, 5 d/wk, for 3 wk, and the left leg mounted to a holder. Through the holder, VIB mice received 45 Hz, ± 0.6 g sinusoidal acceleration without weight bearing. SHAM mice received no vibration. At baseline and 3 wk, muscle cross-sectional area (MCSA and tibial bone properties (epiphysis, metaphysis and diaphysis were assessed by in vivo micro-CT. Bone volume fraction in the metaphysis decreased 12 ± 9% and 7 ± 6% in BTX-VIB and BTX-SHAM, but increased in the VIB and SHAM. There were no differences in dynamic histomorphometry outcomes between BTX-VIB and BTX nor between VIB and SHAM. Thus, vibration did not prevent bone loss induced by a rapid decline in muscle activity nor produce an anabolic effect in normal mice. The daily loading duration was shorter than would be expected from postural muscle activity, and may have been insufficient to prevent bone loss. Based on the approach used in this study, vibration does not prevent bone loss in the absence of muscle activity induced by BTX.

Time-dependent Kohn-Sham approach to quantum electrodynamics

International Nuclear Information System (INIS)

Ruggenthaler, M.; Mackenroth, F.; Bauer, D.

2011-01-01

We prove a generalization of the van Leeuwen theorem toward quantum electrodynamics, providing the formal foundations of a time-dependent Kohn-Sham construction for coupled quantized matter and electromagnetic fields. We circumvent the symmetry-causality problems associated with the action-functional approach to Kohn-Sham systems. We show that the effective external four-potential and four-current of the Kohn-Sham system are uniquely defined and that the effective four-current takes a very simple form. Further we rederive the Runge-Gross theorem for quantum electrodynamics.

Effects of Sumsu (Bufonis venenum) Pharmacopuncture Treatment on Depression in Mice.

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Choi, Min-Ji; Kim, Ka-Na; Lee, Jae-Eun; Suh, Jin-Woo; Kim, Sung-Chul; Kwon, Ki Rok; Cho, Seung-Hun

2014-06-01

The main objective of this study was to evaluate the anti-depressant effects of pharmacopuncture using sumsu (Bufonis venenum). Animals were divided into three groups (control, sham, and experimental), with eight mice per group. The sham and the experimental groups were exposed to 2 hours of immobilization stress daily for 14 days. They were also injected with normal saline (sham) or subjected to pharmacopuncture with sumsu at the acupoints HT7, SP6, and GV20 (experimental). The depression or anxiety-like behaviors of the mice in each group were evaluated 1 day after treatment. There was no difference in locomotor activity between the groups during the open-field test; i.e., all groups had normal motor function. However, the open-field and the forced-swimming tests revealed that depression and anxiety-like behaviors were decreased significantly in the group treated with sumsu pharmacopuncture. Sumsu pharmacopuncture attenuated depressive or anxiety-like behavior in mice stressed with chronic immobilization. These results suggest that sumsu pharmacopuncture has therapeutic potential for treating neuropsychiatric disorders such as anxiety or depression disorder.

Plasma catecholamine and serum gastrin concentrations during sham feeding

DEFF Research Database (Denmark)

Bekker, Carsten; Andersen, D; Kronborg, O

1983-01-01

Plasma adrenaline, plasma noradrenaline and serum gastrin concentrations were measured before and after sham feeding in eight patients with duodenal ulcer and in four normal subjects. No significant change in the concentrations was observed after sham feeding. In three patients with duodenal ulce...... groups. It is concluded that sympathetic nervous activity and serum gastrin concentrations are not influenced by sham feeding in contrast to the influence of insulin hypoglycemia....... an insulin test resulted in a 25-fold rise in plasma adrenaline. The ulcer patients showed significantly higher levels of plasma adrenaline and plasma noradrenaline than the normal subjects both before and after sham feeding, and this difference was probably not caused only by age difference in the two...

Efficacy of Bee Venom Acupuncture for Chronic Low Back Pain: A Randomized, Double-Blinded, Sham-Controlled Trial.

Science.gov (United States)

Seo, Byung-Kwan; Han, Kyungsun; Kwon, Ojin; Jo, Dae-Jean; Lee, Jun-Hwan

2017-11-07

Bee venom acupuncture (BVA) is an effective treatment for chronic low back pain (CLBP) through the pharmacological effects of bee venom and the simultaneous stimulation of acupoints. However, evidence of its efficacy and safety in humans remains unclear. Using a double-blind, randomized study, 54 patients with non-specific CLBP were assigned to the BVA and sham groups. All participants underwent six sessions of real or sham BVA for 3 weeks, in addition to administration of 180 mg of loxonin per day. The primary outcome, that is, "bothersomeness" derived from back pain, was assessed using the visual analog scale. Secondary outcomes included pain intensity, dysfunction related to back pain (Oswestry Disability Index), quality of life (EuroQol 5-Dimension), and depressive mood (Beck's depression inventory). Outcomes were evaluated every week during the treatment period and followed up at weeks 4, 8, and 12. After 3 weeks of the treatment, significant improvements were observed in the bothersomeness, pain intensity, and functional status in the BVA group compared with the sham group. Although minimal adverse events were observed in both groups, subsequent recovery was achieved without treatment. Consequently, our results suggest that it can be used along with conventional pharmacological therapies for the treatment of CLBP.

Endothelial dysfunction of resistance vessels in female apolipoprotein E-deficient mice

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Vasquez Elisardo C

2010-05-01

Full Text Available Abstract Background The effects of hypercholesterolemia on vasomotricity in apolipoprotein E-deficient (ApoE mice, a murine model of spontaneous atherosclerosis, are still unclear. The studies were mostly performed in conductance vessels from male mice fed a high-fat diet. In the present study, we evaluated the endothelial function of resistance vessels from normal C57BL/6 (C57 and hypercholesterolemic (ApoE female mice in both normal and ovariectomized conditions. Methods Twenty week-old C57 and ApoE mice underwent ovariectomy or sham surgery and were studied 30 days later. The vascular reactivities to norepinephrine (NE, 10-9 to 2 × 10-3 mol/L, acetylcholine (ACh and sodium nitroprusside (SNP (10-10 to 10-3 mol/L were evaluated in the isolated mesenteric arteriolar bed through dose-response curves. Results ACh-induced relaxation was significantly reduced (P 50 (-5.67 ± 0.18 vs. -6.23 ± 0.09 mol/L. Ovariectomy caused a significant impairment in ACh-induced relaxation in the C57 group (maximal response: 61 ± 4% but did not worsen the deficient state of relaxation in ApoE animals (maximal response: 39 ± 5%. SNP-induced vasorelaxation and NE-induced vasoconstriction were similar in ApoE and C57 female mice. Conclusion These data show an impairment of endothelial function in the resistance vessels of spontaneously atherosclerotic (ApoE-deficient female mice compared with normal (C57 female mice. The endothelial dysfunction in hypercholesterolemic animals was so marked that ovariectomy, which impaired endothelial function in C57 mice, did not cause additional vascular damage in ApoE-deficient mice.

Direct renin inhibitor ameliorates insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice.

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Fukushima, Arata; Kinugawa, Shintaro; Takada, Shingo; Matsumoto, Junichi; Furihata, Takaaki; Mizushima, Wataru; Tsuda, Masaya; Yokota, Takashi; Matsushima, Shouji; Okita, Koichi; Tsutsui, Hiroyuki

2016-05-15

Insulin resistance can occur as a consequence of heart failure (HF). Activation of the renin-angiotensin system (RAS) may play a crucial role in this phenomenon. We thus investigated the effect of a direct renin inhibitor, aliskiren, on insulin resistance in HF after myocardial infarction (MI). MI and sham operation were performed in male C57BL/6J mice. The mice were divided into 4 groups and treated with sham-operation (Sham, n=10), sham-operation and aliskiren (Sham+Aliskiren; 10mg/kg/day, n=10), MI (n=11), or MI and aliskiren (MI+Aliskiren, n=11). After 4 weeks, MI mice showed left ventricular dilation and dysfunction, which were not affected by aliskiren. The percent decrease of blood glucose after insulin load was significantly smaller in MI than in Sham (14±5% vs. 36±2%), and was ameliorated in MI+Aliskiren (34±5%) mice. Insulin-stimulated serine-phosphorylation of Akt and glucose transporter 4 translocation were decreased in the skeletal muscle of MI compared to Sham by 57% and 69%, and both changes were ameliorated in the MI+Aliskiren group (91% and 94%). Aliskiren administration in MI mice significantly inhibited plasma renin activity and angiotensin II (Ang II) levels. Moreover, (pro)renin receptor expression and local Ang II production were upregulated in skeletal muscle from MI and were attenuated in MI+Aliskiren mice, in tandem with a decrease in superoxide production and NAD(P)H oxidase activities. In conclusion, aliskiren ameliorated insulin resistance in HF by improving insulin signaling in the skeletal muscle, at least partly by inhibiting systemic and (pro)renin receptor-mediated local RAS activation, and subsequent NAD(P)H oxidase-induced oxidative stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Salicylhydroxamic acid (SHAM) inhibition of the DIC-pump in unicellular algae

International Nuclear Information System (INIS)

Goyal, A.; Tolbert, N.E.

1989-01-01

SHAM at 1 or 2 mM inhibits dissolved inorganic carbon (DIC) concentrating mechanisms in unicellular green algae as measured by photosynthetic oxygen evolution or by 14 C-inorganic carbon uptake (using silicone oil centrifugation techniques). This inhibition was reversed by high levels of DIC whereby the cells do not require the concentrating mechanism. SHAM inhibited the DIC-pump, which uses external CO 2 , in three species of algae, Dunaliella tertiolecta, Chlamydomonas reinhardtii, and Scenedesmus obliquus when adapted to low CO 2 and assayed around neutral pH. Scenedesmus adapted to air at pH 9.0 to use external HCO 3 - were not affected by SHAM. It is important to establish low optimum concentrations of SHAM, which varied with the algal species. The mechanism of SHAM inhibition of the CO 2 concentrating process is unknown. SHAM inhibits alternative respiration in these algae, but SHAM may also inhibit other reactions involving H + gradients or transporters associated with the DIC-pump

Variational method for inverting the Kohn-Sham procedure

International Nuclear Information System (INIS)

Kadantsev, Eugene S.; Stott, M.J.

2004-01-01

A procedure based on a variational principle is developed for determining the local Kohn-Sham (KS) potential corresponding to a given ground-state electron density. This procedure is applied to calculate the exchange-correlation part of the effective Kohn-Sham (KS) potential for the neon atom and the methane molecule

Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage

Institute of Scientific and Technical Information of China (English)

Yifan He; Jihong Zhu; Fang Huang; Liu Qin; Wenguo Fan; Hongwen He

2014-01-01

The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltrans-ferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and

Attenuated lung fibrosis in interleukin 6 knock-out mice after C-ion irradiation to lung

International Nuclear Information System (INIS)

Saito-Fujita, Tomoko; Iwakawa, Mayumi; Nakamura, Etsuko; Nakawatari, Miyako; Fujita, Hidetoshi; Moritake, Takashi; Imai, Takashi

2011-01-01

There is a great deal of evidence that a cyclic cascade of inflammatory cytokines, together with the activation of macrophages, is initiated very early after irradiation to develop lung fibrosis in a late phase. To understand the persistent effects of cytokines, the cytokine gene of knock out or transgenic mouse is one of the useful tools. In this study, we evaluated a role of a key molecule, interleukin-6 (IL-6), in the late-phase inflammatory response and subsequent fibrotic changes after irradiation using wild-type (WT) and IL-6 knock out (IL-6 KO) mice. The mice underwent thoracic irradiation with 10 Gy of C-ion beam or sham-irradiation and were examined by histology. Immunoreactivity for IL-6 was induced at the site of bronchiolar epithelium, in pneumocytes and in monocytes by C-ion irradiation. At 24 weeks after irradiation, the infiltration of macrophages, detected by positive immunohistological staining with Mac3 antibody, was observed in alveolar spaces both in WT and IL-6 KO mice. The thickening of bronchiolar and alveolar walls exhibited in WT mice, but not KO mice, and fibrotic changes detected by Masson-Trichrome staining, were observed only in the lungs of WT mice, while it was attenuated in IL-6 KO mice. These results indicated that IL-6 might not be essential for activating macrophages in the late phase, but plays an important role for fibrotic changes of the alveolar wall after irradiation. (author)

Testosterone Depletion by Castration May Protect Mice from Heat-Induced Multiple Organ Damage and Lethality

Directory of Open Access Journals (Sweden)

Ruei-Tang Cheng

2010-01-01

Full Text Available When the vehicle-treated, sham-operated mice underwent heat stress, the fraction survival and core temperature at +4 h of body heating were found to be 5 of 15 and 34.4∘C±0.3∘C, respectively. Castration 2 weeks before the start of heat stress decreased the plasma levels of testosterone almost to zero, protected the mice from heat-induced death (fraction survival, 13/15 and reduced the hypothermia (core temperature, 37.3∘C. The beneficial effects of castration in ameliorating lethality and hypothermia can be significantly reduced by testosterone replacement. Heat-induced apoptosis, as indicated by terminal deoxynucleotidyl- transferase- mediatedαUDP-biotin nick end-labeling staining, were significantly prevented by castration. In addition, heat-induced neuronal damage, as indicated by cell shrinkage and pyknosis of nucleus, to the hypothalamus was also castration-prevented. Again, the beneficial effects of castration in reducing neuronal damage to the hypothalamus as well as apoptosis in multiple organs during heatstroke, were significantly reversed by testosterone replacement. The data indicate that testosterone depletion by castration may protect mice from heatstroke-induced multiple organ damage and lethality.

Igfbp2 Deletion in Ovariectomized Mice Enhances Energy Expenditure but Accelerates Bone Loss.

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DeMambro, Victoria E; Le, Phuong T; Guntur, Anyonya R; Maridas, David E; Canalis, Ernesto; Nagano, Kenichi; Baron, Roland; Clemmons, David R; Rosen, Clifford J

2015-11-01

Previously, we reported sexually dimorphic bone mass and body composition phenotypes in Igfbp2(-/-) mice (-/-), where male mice exhibited decreased bone and increased fat mass, whereas female mice displayed increased bone but no changes in fat mass. To investigate the interaction between IGF-binding protein (IGFBP)-2 and estrogen, we subjected Igfbp2 -/- and +/+ female mice to ovariectomy (OVX) or sham surgery at 8 weeks of age. At 20 weeks of age, mice underwent metabolic cage analysis and insulin tolerance tests before killing. At harvest, femurs were collected for microcomputed tomography, serum for protein levels, brown adipose tissue (BAT) and inguinal white adipose tissue (IWAT) adipose depots for histology, gene expression, and mitochondrial respiration analysis of whole tissue. In +/+ mice, serum IGFBP-2 dropped 30% with OVX. In the absence of IGFBP-2, OVX had no effect on preformed BAT; however, there was significant "browning" of the IWAT depot coinciding with less weight gain, increased insulin sensitivity, lower intraabdominal fat, and increased bone loss due to higher resorption and lower formation. Likewise, after OVX, energy expenditure, physical activity and BAT mitochondrial respiration were decreased less in the OVX-/- compared with OVX+/+. Mitochondrial respiration of IWAT was reduced in OVX+/+ yet remained unchanged in OVX-/- mice. These changes were associated with significant increases in Fgf21 and Foxc2 expression, 2 proteins known for their insulin sensitizing and browning of WAT effects. We conclude that estrogen deficiency has a profound effect on body and bone composition in the absence of IGFBP-2 and may be related to changes in fibroblast growth factor 21.

Oscillating Square Wave Transcranial Direct Current Stimulation (tDCS) Delivered During Slow Wave Sleep Does Not Improve Declarative Memory More Than Sham: A Randomized Sham Controlled Crossover Study.

Science.gov (United States)

Sahlem, Gregory L; Badran, Bashar W; Halford, Jonathan J; Williams, Nolan R; Korte, Jeffrey E; Leslie, Kimberly; Strachan, Martha; Breedlove, Jesse L; Runion, Jennifer; Bachman, David L; Uhde, Thomas W; Borckardt, Jeffery J; George, Mark S

2015-01-01

A 2006 trial in healthy medical students found that anodal slow oscillating tDCS delivered bi-frontally during slow wave sleep had an enhancing effect in declarative, but not procedural memory. Although there have been supporting animal studies, and similar findings in pathological groups, this study has not been replicated, or refuted, in the intervening years. We therefore tested these earlier results for replication using similar methods with the exception of current waveform (square in our study, nearly sinusoidal in the original). Our objective was to test the findings of a 2006 trial suggesting bi-frontal anodal tDCS during slow wave sleep enhances declarative memory. Twelve students (mean age 25, 9 women) free of medical problems underwent two testing conditions (active, sham) in a randomized counterbalanced fashion. Active stimulation consisted of oscillating square wave tDCS delivered during early Non-Rapid Eye Movement (NREM) sleep. The sham condition consisted of setting-up the tDCS device and electrodes, but not turning it on during sleep. tDCS was delivered bi-frontally with anodes placed at F3/F4, and cathodes placed at mastoids. Current density was 0.517 mA/cm(2), and oscillated between zero and maximal current at a frequency of 0.75 Hz. Stimulation occurred during five-five minute blocks with 1-min inter-block intervals (25 min total stimulation). The primary outcomes were both declarative memory consolidation measured by a paired word association test (PWA), and non-declarative memory, measured by a non-dominant finger-tapping test (FTT). We also recorded and analyzed sleep EEG. There was no difference in the number of paired word associations remembered before compared to after sleep [(active = 3.1 ± 3.0 SD more associations) (sham = 3.8 ± 3.1 SD more associations)]. Finger tapping improved, (non-significantly) following active stimulation [(3.6 ± 2.7 SD correctly typed sequences) compared to sham stimulation (2.3 ± 2.2 SD correctly typed

Use of 'sham' radiotherapy in randomized clinical trials

International Nuclear Information System (INIS)

Schwarz, F.; Christie, D.

2008-01-01

The objective of this systematic review was to identify quality trials that use sham radiotherapy in their design and review them to determine its potential value. The Cochrane Library, Pubmed and a Reference Search served as data sources. Trials were included if they met a minimum quality score of 3 on a validated assessment instrument (which assesses randomization, control and blinding) and if they compared sham radiotherapy to active treatment. External beam therapy and brachytherapy trials were considered. Twenty-six trials were identified, collectively including 2663 participants in the period of 1970-2004. All the trials studied the value of radiotherapy for treatment or prevention of benign diseases, including multiple sclerosis, coronary artery restenosis, age-related macular degeneration and Graves' ophthalmopathy. There were no trials relating to the use of radiotherapy in the treatment of malignancy. This review showed that it is possible to carry out sham radiotherapy with due regard for ethical concerns, with effective blinding and high levels of patient acceptance. Large sample sizes with multicentre trial designs were achievable. Although the statistical philosophy for using sham radiotherapy in trials is legitimate, it is no longer routinely used.

Electronically switchable sham transcranial magnetic stimulation (TMS system.

Directory of Open Access Journals (Sweden)

Fumiko Hoeft

Full Text Available Transcranial magnetic stimulation (TMS is increasingly being used to demonstrate the causal links between brain and behavior in humans. Further, extensive clinical trials are being conducted to investigate the therapeutic role of TMS in disorders such as depression. Because TMS causes strong peripheral effects such as auditory clicks and muscle twitches, experimental artifacts such as subject bias and placebo effect are clear concerns. Several sham TMS methods have been developed, but none of the techniques allows one to intermix real and sham TMS on a trial-by-trial basis in a double-blind manner. We have developed an attachment that allows fast, automated switching between Standard TMS and two types of control TMS (Sham and Reverse without movement of the coil or reconfiguration of the setup. We validate the setup by performing mathematical modeling, search-coil and physiological measurements. To see if the stimulus conditions can be blinded, we conduct perceptual discrimination and sensory perception studies. We verify that the physical properties of the stimulus are appropriate, and that successive stimuli do not contaminate each other. We find that the threshold for motor activation is significantly higher for Reversed than for Standard stimulation, and that Sham stimulation entirely fails to activate muscle potentials. Subjects and experimenters perform poorly at discriminating between Sham and Standard TMS with a figure-of-eight coil, and between Reverse and Standard TMS with a circular coil. Our results raise the possibility of utilizing this technique for a wide range of applications.

Kinetics of small lymphocytes in normal and nude mice after splenectomy

DEFF Research Database (Denmark)

Hougen, H P; Hansen, F; Jensen, E K

1977-01-01

Autoradiography and various quantitations on lymphoid tissues have been used to evaluate the kinetics of small lymphocytes in normal (+/nu or +/+) and congenitally athymic nude (nu/nu) NMRI mice 1 month after splenectomy or sham-splenectomy. The results indicate that splenectomy causes depressed...... thymic activity and diminished numbers of T lymphocytes in peripheral lymphoid tissues. The total number of cells in these tissues as well as the blast cell activity, were within normal limits. Bone marrow lymphocyte numbers and kinetics as well as blood lymphocyte levels in splenectomized and sham......-splenectomized normal animals were comparable. Blood lymphocyte numbers were at normal levels in splenectomized nude mice, in spite of reduced numbers of bone marrow and thoracic duct lymphocytes. It is suggested that increased number of newly-formed lymphocytes, found in lymph nodes and blood of splenectomized mice...

Electric field measurement of two commercial active/sham coils for transcranial magnetic stimulation.

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Smith, James Evan; Peterchev, Angel V

2018-06-22

Sham TMS coils isolate the ancillary effects of their active counterparts, but typically induce low-strength electric fields (E-fields) in the brain, which could be biologically active. We measured the E-fields induced by two pairs of commonly-used commercial active/sham coils. Approach: E-field distributions of the active and sham configurations of the Magstim 70 mm AFC and MagVenture Cool-B65 A/P coils were measured over a 7-cm-radius, hemispherical grid approximating the cortical surface. Peak E-field strength was recorded over a range of pulse amplitudes. Main results: The Magstim and MagVenture shams induce peak E-fields corresponding to 25.3% and 7.72% of their respective active values. The MagVenture sham has an E-field distribution shaped like its active counterpart. The Magstim sham induces nearly zero E-field under the coil's center, and its peak E-field forms a diffuse oval 3-7 cm from the center. Electrical scalp stimulation paired with the MagVenture sham is estimated to increase the sham E-field in the brain up to 10%. Significance: Different commercial shams induce different E-field strengths and distributions in the brain, which should be considered in interpreting outcomes of sham stimulation. © 2018 IOP Publishing Ltd.

Effect of whole-body vibration and insulin-like growth factor-I on muscle paralysis-induced bone degeneration after botulinum toxin injection in mice.

Science.gov (United States)

Niehoff, Anja; Lechner, Philipp; Ratiu, Oana; Reuter, Sven; Hamann, Nina; Brüggemann, Gert-Peter; Schönau, Eckhard; Bloch, Wilhelm; Beccard, Ralf

2014-04-01

Botulinum toxin A (BTX)-induced muscle paralysis results in pronounced bone degradation with substantial bone loss. We hypothesized that whole-body vibration (WBV) and insulin-like growth factor-I (IGF-I) treatment can counteract paralysis-induced bone degradation following BTX injections by activation of the protein kinase B (Akt) signaling pathway. Female C57BL/6 mice (n = 60, 16 weeks) were assigned into six groups (n = 10 each): SHAM, BTX, BTX+WBV, BTX+IGF-I, BTX+WBV+IGF-I, and a baseline group, which was killed at the beginning of the study. Mice received a BTX (1.0 U/0.1 mL) or saline (SHAM) injection in the right hind limb. The BTX+IGF-I and BTX+WBV+IGF-I groups obtained daily subcutaneous injections of human IGF-I (1 μg/day). The BTX+WBV and BTX+WBV+IGF-I groups underwent WBV (25 Hz, 2.1 g, 0.83 mm) for 30 min/day, 5 days/week for 4 weeks. Femora were scanned by pQCT, and mechanical properties were determined. On tibial sections TRAP staining, static histomorphometry, and immunohistochemical staining against Akt, phospho-Akt, IGF-IR (IGF-I receptor), and phospho-IGF-IR were conducted. BTX injection decreased trabecular and cortical bone mineral density. The WBV and WBV+IGF-I groups showed no difference in trabecular bone mineral density compared to the SHAM group. The phospho-IGF-IR and phospho-Akt stainings were not differentially altered in the injected hind limbs between groups. We found that high-frequency, low-magnitude WBV can counteract paralysis-induced bone loss following BTX injections, while we could not detect any effect of treatment with IGF-I.

Enzymatically modified isoquercitrin supplementation intensifies plantaris muscle fiber hypertrophy in functionally overloaded mice.

Science.gov (United States)

Kohara, Akiko; Machida, Masanao; Setoguchi, Yuko; Ito, Ryouichi; Sugitani, Masanori; Maruki-Uchida, Hiroko; Inagaki, Hiroyuki; Ito, Tatsuhiko; Omi, Naomi; Takemasa, Tohru

2017-01-01

Enzymatically modified isoquercitrin (EMIQ) is produced from rutin using enzymatic hydrolysis followed by treatment with glycosyltransferase in the presence of dextrin to add glucose residues. EMIQ is absorbed in the same way as quercetin, a powerful antioxidant reported to prevent disused muscle atrophy by targeting mitochondria and to have ergogenic effects. The present study investigated the effect of EMIQ on skeletal muscle hypertrophy induced by functional overload. In Study 1, 6-week-old ICR male mice were divided into 4 groups: sham-operated control, sham-operated EMIQ, overload-operated control, and overload-operated EMIQ groups. In Study 2, mice were divided into 3 groups: overload-operated whey control, overload-operated whey/EMIQ (low dose), and overload-operated whey/EMIQ (high dose) groups. The functional overload of the plantaris muscle was induced by ablation of the synergist (gastrocnemius and soleus) muscles. EMIQ and whey protein were administered with food. Three weeks after the operation, the cross-sectional area and minimal fiber diameter of the plantaris muscle fibers were measured. In Study 1, functional overload increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ supplementation significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle in both the sham-operated and overload-operated groups. In Study 2, EMIQ supplementation combined with whey protein administration significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ, even when administered as an addition to whey protein supplementation, significantly intensified the fiber hypertrophy of the plantaris muscle in functionally overloaded mice. EMIQ supplementation also induced fiber hypertrophy of the plantaris in sham-operated mice.

Time Course of Influence by Ovariectomy and Calcium Diet on Bone Properties in Mice

OpenAIRE

Minematsu, Akira; Yoshimura, Osamu; Yotsuji, Hirofumi; Ichigo, Hirozo; Kobayashi, Ryuji; Sasaki, Hisato; Tanaka, Sachiko; Kanemura, Naohiko; Shirahama, Kunji; Miyamoto, Hidetaka

2001-01-01

This study was investigated the influence by ovariectomy (OVX) and calcium diet on bone properties in eighty-one female ICR strain mice with age of 5 weeks. The animals were randomly assigned to sham operation (SHAM), OVX, SHAM+low Ca intake (L.Ca) and OVX+L.Ca group. They were euthanized with lethal dose of pentobarbital sodium at day 50, 100 and 140 post-operatively. For determining the bone properties, both femur and tibial bones were excised from the hind limb, and removed off surrounding...

A Kohn-Sham system at zero temperature

International Nuclear Information System (INIS)

Cornean, H; Hoke, K; Neidhardt, H; Racec, P N; Rehberg, J

2008-01-01

A one-dimensional Kohn-Sham system for spin particles is considered which effectively describes semiconductor nanostructures, and which is investigated at zero temperature. We prove the existence of solutions and derive a priori estimates. For this purpose we find estimates for eigenvalues of the Schroedinger operator with effective Kohn-Sham potential and obtain W 1,2 -bounds of the associated particle density operator. Afterwards, compactness and continuity results allow us to apply Schauder's fixed point theorem. In the case of vanishing exchange-correlation potential uniqueness is shown by monotonicity arguments. Finally, we investigate the behavior of the system if the temperature approaches zero

Changes of microRNA profile and microRNA-mRNA regulatory network in bones of ovariectomized mice.

Science.gov (United States)

An, Jee Hyun; Ohn, Jung Hun; Song, Jung Ah; Yang, Jae-Yeon; Park, Hyojung; Choi, Hyung Jin; Kim, Sang Wan; Kim, Seong Yeon; Park, Woog-Yang; Shin, Chan Soo

2014-03-01

Growing evidence shows the possibility of a role of microRNAs (miRNA) in regulating bone mass. We investigated the change of miRNAs and mRNA expression profiles in bone tissue in an ovariectomized mice model and evaluated the regulatory mechanism of bone mass mediated by miRNAs in an estrogen-deficiency state. Eight-week-old female C3H/HeJ mice underwent ovariectomy (OVX) or sham operation (Sham-op), and their femur and tibia were harvested to extract total bone RNAs after 4 weeks for microarray analysis. Eight miRNAs (miR-127, -133a, -133a*, -133b, -136, -206, -378, -378*) were identified to be upregulated after OVX, whereas one miRNA (miR-204) was downregulated. Concomitant analysis of mRNA microarray revealed that 658 genes were differentially expressed between OVX and Sham-op mice. Target prediction of differentially expressed miRNAs identified potential targets, and integrative analysis using the mRNA microarray results showed that PPARγ and CREB pathways are activated in skeletal tissues after ovariectomy. Among the potential candidates of miRNA, we further studied the role of miR-127 in vitro, which exhibited the greatest changes after OVX. We also studied the effects of miR-136, which has not been studied in the context of bone mass regulation. Transfection of miR-127 inhibitor has enhanced osteoblastic differentiation in UAMS-32 cells as measured by alkaline phosphatase activities and mRNA expression of osteoblast-specific genes, whereas miR-136 precursor has inhibited osteoblastic differentiation. Furthermore, transfection of both miR-127 and miR-136 inhibitors enhanced the osteocyte-like morphological changes and survival in MLO-Y4 cells, whereas precursors of miR-127 and -136 have aggravated dexamethasone-induced cell death. Both of the precursors enhanced osteoclastic differentiation in bone marrow macrophages, indicating that both miR-127 and -136 are negatively regulating bone mass. Taken together, these results suggest a novel insight into the

Radiation-induced pulmonary endothelial dysfunction and hydroxyproline accumulation in four strains of mice

International Nuclear Information System (INIS)

Ward, W.F.; Sharplin, J.; Franko, A.J.; Hinz, J.M.

1989-01-01

C57BL mice exposed to 14 Gy of whole-thorax irradiation develop significant histologic lung fibrosis within 52 weeks, whereas CBA and C3H mice do not exhibit substantial fibrosis during this time. The purpose of the present study was to determine whether this strain-dependent difference in radiation histopathology is associated with genetic differences in pulmonary endothelial metabolic activity or in endothelial radioresponsiveness. C57BL/6J, C57BL/10J, CBA/J, and C3H/HeJ mice were sacrificed 12 weeks after exposure to 0 or 14 Gy of 300-kV X rays to the whole thorax. Lung angiotensin converting enzyme (ACE) activity and plasminogen activator (PLA) activity were measured as indices of pulmonary endothelial function; and lung hydroxyproline (HP) content served as an index of pulmonary fibrosis. Lung ACE and PLA activities in sham-irradiated C57BL/6J and CB57BL/10J mice were only half as high as those in sham-irradiated CBA/J and C3H/HeJ mice. Exposure to 14 Gy of X rays produced a slight but nonsignificant reduction in lung ACE and PLA activity in the C57BL strains, and a significant reduction in the CBA/J and C3H/HeJ mice. Even after 14 Gy, however, lung ACE and PLA activities in CBA/J and C3H/HeJ mice were higher than those in sham-irradiated C57BL/6J and C57BL/10J mice. Lung HP content in all four strains increased significantly after irradiation, but this increase was accompanied by an increase in lung wet weight. As a result, HP concentration (per milligram wet weight) remained constant or increased slightly in both C57BL strains and actually decreased in the CBA/J and C3H/HeJ mice. These data demonstrate significant genetic differences in both intrinsic pulmonary endothelial enzyme activity and endothelial radioresponsiveness among the four strains of mice

Does a single session of electroconvulsive therapy alter the neural response to emotional faces in depression? A randomised sham-controlled functional magnetic resonance imaging study

DEFF Research Database (Denmark)

Miskowiak, Kamilla W; Kessing, Lars V; Ott, Caroline V

2017-01-01

neurocognitive bias in major depressive disorder. Patients with major depressive disorder were randomised to one active ( n=15) or sham electroconvulsive therapy ( n=12). The following day they underwent whole-brain functional magnetic resonance imaging at 3T while viewing emotional faces and performed facial...... expression recognition and dot-probe tasks. A single electroconvulsive therapy session had no effect on amygdala response to emotional faces. Whole-brain analysis revealed no effects of electroconvulsive therapy versus sham therapy after family-wise error correction at the cluster level, using a cluster...... to faces after a single electroconvulsive therapy session, the observed trend changes after a single electroconvulsive therapy session point to an early shift in emotional processing that may contribute to antidepressant effects of electroconvulsive therapy....

Effectiveness of Traditional Chinese Acupuncture versus Sham Acupuncture: a Systematic Review.

Science.gov (United States)

Carlos, Luís; Cruz, Lóris Aparecida Prado da; Leopoldo, Vanessa Cristina; Campos, Fabrício Ribeiro de; Almeida, Ana Maria de; Silveira, Renata Cristina de Campos Pereira

2016-08-15

to identify and synthesize the evidence from randomized clinical trials that tested the effectiveness of traditional Chinese acupuncture in relation to sham acupuncture for the treatment of hot flashes in menopausal women with breast cancer. systematic review guided by the recommendations of the Cochrane Collaboration. Citations were searched in the following databases: MEDLINE via PubMed, Web of Science, CENTRAL, CINAHL, and LILACS. A combination of the following keywords was used: breast neoplasm, acupuncture, acupuncture therapy, acupuncture points, placebos, sham treatment, hot flashes, hot flushes, menopause, climacteric, and vasomotor symptoms. a total of 272 studies were identified, five of which were selected and analyzed. Slight superiority of traditional acupuncture compared with sham acupuncture was observed; however, there were no strong statistical associations. the evidence gathered was not sufficient to affirm the effectiveness of traditional acupuncture compared with sham acupuncture. identificar e sintetizar as evidências oriundas de ensaios clínicos randomizados que testaram a efetividade da acupuntura tradicional chinesa em relação à sham acupuntura para o tratamento dos fogachos em mulheres com câncer de mama no climatério. revisão sistemática guiada pelas recomendações da Colaboração Cochrane. A busca foi realizada nas bases de dados: MEDLINE via PubMed, Web of Science, CENTRAL Cochrane, CINAHL e LILACS. Adotou-se a combinação dos descritores: breast neoplasm, acupuncture, acupuncture therapy, acupuncture points, placebos, sham treatment, hot flashes, hot flushes, menopause, climacteric, vasomotor symptoms. foram identificados 272 estudos, sendo 5 selecionados e analisados. Foi observada discreta superioridade da acupuntura tradicional em relação à sham, entretanto, sem fortes associações estatísticas. as evidências obtidas não foram suficientes para afirmar quanto à efetividade da acupuntura tradicional em relação �

A single-center, prospective, double-blind, sham-controlled, randomized study of the effect of a vibrating capsule on colonic transit in patients with chronic constipation.

Science.gov (United States)

Nelson, A D; Camilleri, M; Acosta, A; Boldingh, A; Busciglio, I; Burton, D; Ryks, M; Zinsmeister, A R

2017-07-01

In an open-label study of 26 patients with IBS-C and chronic constipation, treatment with a vibrating (VIBRANT) capsule twice a week for 7.5 weeks resulted in 88.5% responders. Effects on colonic transit are unclear. We aimed to compare effects of VIBRANT and sham capsule treatment on colonic transit in patients with functional constipation. Patients with functional constipation (Rome III criteria) were randomized to VIBRANT or sham capsule treatment for 8 weeks and underwent scintigraphic colonic transit measurements during week 8. We estimated the overall rate of colonic transit from the slope of progression of colonic geometric center over 48 hours. The capsule was activated 8 hours after ingestion, and the vibration sequence included 240 cycles. There were no significant group differences in overall colonic transit [GC48, 2.76 (IQR 2.42-4.03) for sham group and 3.46 (2.55-4.61) for active treatment group (P=.13)]. Additionally, the progression of the isotope through the colon was numerically faster, though not significantly different (slope, P=.14) in the VIBRANT capsule group compared to the sham group. Three participants in the VIBRANT capsule group had accelerated colonic transit at 32 hours and faster colonic transit slope compared to the 95th percentile of the sham group. Although there were no group differences between VIBRANT and sham capsule treatment on colonic transit, at least one (and possibly three) of 12 patients receiving the VIBRANT capsule had faster colonic transit. The vibration parameters to accelerate colonic transit in patients with functional constipation require further optimization. © 2017 John Wiley & Sons Ltd.

The effect of sex differences on induction of intestinal metaplasia in x-ray irradiated rats

International Nuclear Information System (INIS)

Watanabe, Hiromitsu; Takizawa, Shoichi; Terada, Yoritake; Naito, Masashi; Naito, Yukiko

1980-01-01

The effects of sex differences and ovarian resection on induction of intestinal metaplasia in x-ray irradiated mice were discussed. 1,000 rad of x-ray was irradiated to the stomach of female and male mice twice at intervals of 3 days. The range of intestinal metaplasia in male mice was wider than that in female mice. A total of 400 rad was irradiated to the whole body of mice which underwent ovarian resection (group 1), mice which underwent autotransplantation of the ovary after ovarian resection (group 2), and mice which underwent sham-ovarian resection (group 3). The incidence of intestinal metaplasia in the group 1 was significantly higher than that in the group 3. The weight of the uterus decreased gradually in order of the group 3, group 2, and group 1. It was suggested from above-mentioned results that disappearance or lowering of femal sex hormones, that is, male or androphacy, induced intestinal metaplasia. (Tsunoda, M.)

[Thinking on designation of sham acupuncture in clinical research].

Science.gov (United States)

Pan, Li-Jia; Chen, Bo; Zhao, Xue; Guo, Yi

2014-01-01

Randomized controlled trials (RCT) is the source of the raw data of evidence-based medicine. Blind method is adopted in most of the high-quality RCT. Sham acupuncture is the main form of blinded in acupuncture clinical trial. In order to improve the quality of acupuncture clinical trail, based on the necessity of sham acupuncture in clinical research, the current situation as well as the existing problems of sham acupuncture, suggestions were put forward from the aspects of new way and new designation method which can be adopted as reference, and factors which have to be considered during the process of implementing. Various subjective and objective factors involving in the process of trial should be considered, and used of the current international standards, try to be quantification, and carry out strict quality monitoring.

Combined effects of radon inhalation and antioxidant vitamin administration on acute alcohol-induced hepatopathy in mice

International Nuclear Information System (INIS)

Etani, Reo; Kataoka, Takahiro; Nishiyama, Yuichi; Takata, Yuji; Yamaoka, Kiyonori

2015-01-01

It has been reported that radon inhalation activates antioxidative functions in liver and has an antioxidative effect against hepatopathy similar to that of the antioxidative effects of ascorbic acid (VC) or α-tocopherol (VE). In this study, we examined the combined effects of radon inhalation and antioxidant vitamin administration on acute alcohol-induced hepatopathy in mice. ICR mice were subjected to intraperitoneal (i.p.) administration of alcohol after pretreating with air only (sham) or radon at a concentration of approximately 2000 Bq/m 3 for 24 hours and i.p. administration of VC (300 mg/kg body weight) or VE (300 mg/kg body weight). In mice injected with alcohol, the combined radon and antioxidant vitamins treatment significantly decreased the activities of glutamic oxaloacetic transaminase in serum compared to not only the alcohol-administered group (sham group), but also the radon inhalation with alcohol administration group or the vitamin and alcohol administration group. In addition, radon inhalation significantly increased the antioxidant level, in such as the catalase activity and the total glutathione content in liver compared to the sham group. These results suggested that the combined radon and antioxidant vitamin treatment could effectively inhibit alcohol-induced hepatopathy in mice without any antagonizing action. (author)

SHAM beyond clustering: new tests of galaxy–halo abundance matching with galaxy groups

Energy Technology Data Exchange (ETDEWEB)

Hearin, Andrew P.; Zentner, Andrew R.; Berlind, Andreas A.; Newman, Jeffrey A.

2013-05-27

We construct mock catalogs of galaxy groups using subhalo abundance matching (SHAM) and undertake several new tests of the SHAM prescription for the galaxy-dark matter connection. All SHAM models we studied exhibit significant tension with galaxy groups observed in the Sloan Digital Sky Survey (SDSS). The SHAM prediction for the field galaxy luminosity function (LF) is systematically too dim, and the group galaxy LF systematically too bright, regardless of the details of the SHAM prescription. SHAM models connecting r-band luminosity, Mr, to Vacc, the maximum circular velocity of a subhalo at the time of accretion onto the host, faithfully reproduce galaxy group abundance as a function of richness, g(N). However, SHAM models connecting Mr with Vpeak, the peak value of Vmax over the entire merger history of the halo, over-predict galaxy group abundance. Our results suggest that no SHAM model can simultaneously reproduce the observed g(N) and two-point projected galaxy clustering. Nevertheless, we also report a new success of SHAM: an accurate prediction for Phi(m12), the abundance of galaxy groups as a function of magnitude gap m12, defined as the difference between the r-band absolute magnitude of the two brightest group members. We show that it may be possible to use joint measurements of g(N) and Phi(m12) to tightly constrain the details of the SHAM implementation. Additionally, we show that the hypothesis that the luminosity gap is constructed via random draws from a universal LF provides a poor description of the data, contradicting recent claims in the literature. Finally, we test a common assumption of the Conditional Luminosity Function (CLF) formalism, that the satellite LF need only be conditioned by the brightness of the central galaxy. We find this assumption to be well-supported by the observed Phi(m12).

Long Non-Coding RNA Malat-1 Is Dispensable during Pressure Overload-Induced Cardiac Remodeling and Failure in Mice.

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Tim Peters

Full Text Available Long non-coding RNAs (lncRNAs are a class of RNA molecules with diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases and in particular heart failure is still in its infancy. The exceptionally well conserved nuclear lncRNA Metastasis associated in lung adenocarcinoma transcript 1 (Malat-1 is a regulator of mRNA splicing and highly expressed in the heart. Malat-1 modulates hypoxia-induced vessel growth, activates ERK/MAPK signaling, and scavenges the anti-hypertrophic microRNA-133. We therefore hypothesized that Malat-1 may act as regulator of cardiac hypertrophy and failure during cardiac pressure overload induced by thoracic aortic constriction (TAC in mice.Absence of Malat-1 did not affect cardiac hypertrophy upon pressure overload: Heart weight to tibia length ratio significantly increased in WT mice (sham: 5.78±0.55, TAC 9.79±1.82 g/mm; p<0.001 but to a similar extend also in Malat-1 knockout (KO mice (sham: 6.21±1.12, TAC 8.91±1.74 g/mm; p<0.01 with no significant difference between genotypes. As expected, TAC significantly reduced left ventricular fractional shortening in WT (sham: 38.81±6.53%, TAC: 23.14±11.99%; p<0.01 but to a comparable degree also in KO mice (sham: 37.01±4.19%, TAC: 25.98±9.75%; p<0.05. Histological hallmarks of myocardial remodeling, such as cardiomyocyte hypertrophy, increased interstitial fibrosis, reduced capillary density, and immune cell infiltration, did not differ significantly between WT and KO mice after TAC. In line, the absence of Malat-1 did not significantly affect angiotensin II-induced cardiac hypertrophy, dysfunction, and overall remodeling. Above that, pressure overload by TAC significantly induced mRNA levels of the hypertrophy marker genes Nppa, Nppb and Acta1, to a similar extend in both genotypes. Alternative splicing of Ndrg2 after TAC was apparent in WT (isoform ratio

Adeno-associated Virus Serotype 9 - Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction.

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Knezevic, Tijana; Myers, Valerie D; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K; Gordon, Jennifer; Weiner, Kristen N; Rabinowitz, Joseph; Ramsey, Frederick V; Tilley, Douglas G; Khalili, Kamel; Cheung, Joseph Y; Feldman, Arthur M

2016-12-01

The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. MI-BAG3 mice demonstrated a significantly (p BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (pBAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

Adeno-associated Virus Serotype 9 – Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction

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Knezevic, Tijana; Myers, Valerie D.; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K.; Gordon, Jennifer; Weiner, Kristen N.; Rabinowitz, Joseph; Ramsey, Frederick V.; Tilley, Douglas G.; Khalili, Kamel; Cheung, Joseph Y.; Feldman, Arthur M.

2016-01-01

Objectives The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. Background BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Methods Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. Results MI-BAG3 mice demonstrated a significantly (p BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (pBAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure. PMID:28164169

A multilevel correction adaptive finite element method for Kohn-Sham equation

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Hu, Guanghui; Xie, Hehu; Xu, Fei

2018-02-01

In this paper, an adaptive finite element method is proposed for solving Kohn-Sham equation with the multilevel correction technique. In the method, the Kohn-Sham equation is solved on a fixed and appropriately coarse mesh with the finite element method in which the finite element space is kept improving by solving the derived boundary value problems on a series of adaptively and successively refined meshes. A main feature of the method is that solving large scale Kohn-Sham system is avoided effectively, and solving the derived boundary value problems can be handled efficiently by classical methods such as the multigrid method. Hence, the significant acceleration can be obtained on solving Kohn-Sham equation with the proposed multilevel correction technique. The performance of the method is examined by a variety of numerical experiments.

Splenectomy Versus Sham Splenectomy in a Swine Model of Controlled Hemorrhagic Shock.

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Boysen, Søren R; Caulkett, Nigel A; Brookfield, Caroline E; Warren, Amy; Pang, Jessica M

2016-10-01

Splenectomy is controversial in acute hemorrhagic shock models. To compare splenectomized (SP) versus sham-splenectomized (SSP) swine during acute controlled hemorrhage. Twenty-six male Landrace White swine (mean body weight ± standard deviation, 33.8 ± 2.9 kg) were used. Ethics approval was obtained. Landrace swine underwent splenectomy (n = 13) or sham-splenectomy (n = 13), were bled to mean arterial blood pressure (MAP) of 40 mm Hg, which was held for 60 min, given 125 mL IV RescueFlow, held for a further 60 min, given whole blood, and held for a final 60 min. Tissue oxygen saturation, thromboelastography, oncotic pressure, urine volume and specific gravity, complete blood count, serum chemistry, body temperature, hematocrit, total solids, arterial and mixed venous blood gas, bispectral index, SAP, MAP, DAP, cardiac index, total blood volume (TBV) removed and returned, rate of hemorrhage and transfusion, spleen weight, heart rate (HR), arterial pH, lactate, PaO2, PaCO2, respiratory rate, cranial mesenteric and renal artery blood flow were recorded. Groups were compared using two-way ANOVA with post hoc Bonferroni (P splenectomy for the duration of the experiment (P splenectomy (P Splenectomy likely accounts for the transient increase in hematocrit and the higher HR in SP swine prior to hemorrhage, and the differences in TBV removed between the two groups during hemorrhage. With a fixed end point model using a moderate rate of acute hemorrhage and an MAP of 40 mm Hg, splenectomy is not necessary and may confound results.

Miso (Japanese soybean paste) soup attenuates salt-induced sympathoexcitation and left ventricular dysfunction in mice with chronic pressure overload.

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Ito, Koji; Hirooka, Yoshitaka; Sunagawa, Kenji

2014-02-01

The hypothalamic mineralocorticoid receptor (MR)-angiotensin II type 1 receptor (AT1R) pathway is activated in mice with chronic pressure overload (CPO). When this activation is combined with high salt intake, it leads to sympathoexcitation, hypertension, and left ventricular (LV) dysfunction. Salt intake is thus an important factor that contributes to heart failure. Miso, a traditional Japanese food made from fermented soybeans, rice, wheat, or oats, can attenuate salt-induced hypertension in rats. However, its effects on CPO mice with salt-induced sympathoexcitation and LV dysfunction are unclear. Here, we investigated whether miso has protective effects in these mice. We also evaluated mechanisms associated with the hypothalamic MR-AT1R pathway. Aortic banding was used to produce CPO, and a sham operation was performed for controls. At 2 weeks after surgery, the mice were given water containing high NaCl levels (0.5%, 1.0%, and 1.5%) for 4 weeks. The high salt loading in CPO mice increased excretion of urinary norepinephrine (uNE), a marker of sympathetic activity, in an NaCl concentration-dependent manner; however, this was not observed in Sham mice. Subsequently, CPO mice were administered 1.0% NaCl water (CPO-H) or miso soup (1.0% NaCl equivalent, CPO-miso). The expression of hypothalamic MR, serum glucocorticoid-induced kinase-1 (SGK-1), and AT1R was higher in the CPO-H mice than in the Sham mice; however, the expression of these proteins was attenuated in the CPO-miso group. Although the CPO-miso mice had higher sodium intake, salt-induced sympathoexcitation was lower in these mice than in the CPO-H group. Our findings indicate that regular intake of miso soup attenuates salt-induced sympathoexcitation in CPO mice via inhibition of the hypothalamic MR-AT1R pathway.

Physical interpretation and evaluation of the Kohn-Sham and Dyson components of the epsilon-I relations between the Kohn-Sham orbital energies and the ionization potentials

NARCIS (Netherlands)

Gritsenko, O.V.; Braida, B.; Baerends, E.J.

2003-01-01

Theoretical and numerical insight was gained into the relations between the Kohn-Sham orbital energies and relaxed vertical ionization potentials. A connection was made between the Kohn-Sham and Dyson one-electron theories. It was established that the energies of the occupied KS orbitals are

Effect of semiconductor GaAs laser irradiation on pain perception in mice

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Zarkovic, N.; Manev, H.; Pericic, D.; Skala, K.; Jurin, M.; Persin, A.; Kubovic, M.

1989-01-01

The influence of subacute exposure (11 exposures within 16 days) of mice to the low power (GaAs) semiconductive laser-stimulated irradiation on pain perception was investigated. The pain perception was determined by the latency of foot-licking or jumping from the surface of a 53 degrees C hot plate. Repeated hot-plate testing resulted in shortening of latencies in both sham- and laser-irradiated mice. Laser treatment (wavelength, 905 nm; frequency, 256 Hz; irradiation time, 50 sec; pulse duration, 100 nsec; distance, 3 cm; peak irradiance, 50 W/cm2 in irradiated area; and total exposure, 0.41 mJ/cm2) induced further shortening of latencies, suggesting its stimulatory influence on pain perception. Administration of morphine (20 mg/kg) prolonged the latency of response to the hot plate in both sham- and laser-irradiated mice. This prolongation tended to be lesser in laser-irradiated animals. Further investigations are required to elucidate the mechanism of the observed effect of laser.

Effect of Mobile Phone Microwaves on Fetal Period of Balb-C Mice in Histological Characteristics of Hippocampus and Learning Behaviors

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Ali Moghimi

2009-09-01

Full Text Available Objective(sThe possible risks of radio-frequency electromagnetic fields (EMF for the living organisms and human body are a growing concern for our society. In this study, we examined the possibility of changes in working memory and hippocampal histological characteristics effects in mice brain following whole body exposure to microwave radiation.Materials and MethodsDuring gestation period, we exposed mice for 4 hr to Global system for mobile communications (GSM, Specific Absorption Rate (SAR of 200 mW/kg. Pregnant control mice were sham-exposed or free in a cage without further restraining. Three month after exposure animals were prepared for behavioral (Radial Arm Maze (RAM and Morris Water Maze (MWM and histological studies.ResultsThe results showed that microwave exposed mice were slower than sham, and control in finding the platform. Analyses of error rates in RAM and MWM performance revealed significant differences which emphasize the effect of acute exposure to pulsed microwaves in deficit of spatial reference memory in the mice. However in this study exposed group didn’t show any statistically significant loss of hippocampal CA1, CA3 neurons versus controls or sham. ConclusionWe conclude that there is evidence from the current study that exposure to MW radiation under parameters examined caused decrements in the ability of mice to learn the spatial memory task.

Genistein Protects Against Biomarkers of Delayed Lung Sequelae in Mice Surviving High-Dose Total Body Irradiation

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DAY, Regina M.; BARSHISHAT-KUPPER, Michal; MOG, Steven R.; MCCART, Elizabeth A.; PRASANNA, P. G. S.; DAVIS, Thomas A.; LANDAUER, Michael R.

2008-01-01

The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60Co, 0.6 Gy/min). Experimental groups were: No treatment + Sham (NC), Vehicle + Sham (VC), Genistein + Sham (GC), Radiation only (NR), Vehicle + Radiation (VR), Genistein + Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13–28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries. PMID:18434686

Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation

International Nuclear Information System (INIS)

Day, R.M.; Barshishat-Kupper, M.; Mog, S.R.; Mccart, E.A.; Prasanna, P.G.S.; Landauer, M.R.; Davis, T.A.

2008-01-01

The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60 Co, 0.6 Gy/min). Experimental groups were: No treatment+Sham (NC), Vehicle+Sham (VC), Genistein+Sham (GC), Radiation only (NR), Vehicle+Radiation (VR), Genistein+Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13-28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries. (author)

Effects of Kerack used in addict Iranian people on fertility of adult mice

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Mehdi Amini

2013-08-01

Full Text Available Background: Infertility is one of the most serious social problems. Illicit drug use can be an important cause of male factor infertility. Kerack which its use is rising up in Iran refers to a high purity street-level heroin (heroin Kerack. Heroin Kerack used in Iran is an opioid and has harmful effects on body organs. The aim of this study is to investigate the effects of Kerack used in Iran on fertility adult mice.Methods: In this study, 25 male mice were divided into five groups (control, sham and three experimental. Experimental groups of Kerack-dependent mice (received ascend-ing dose of Kerack for seven days were divided into three categories, experimental I, II and III. Experimental I was given Kerack at a dose of 5 mg/kg, experimental II 35 mg/kg and experimental III 70 mg/kg, intraperitoneally twice a day for a period of 35 days. The sham group received normal saline and lemon juice (2.6 µl/ml whilst the control group just received water and food. Mice were then scarified and sperm removed from cauda epididymis were analyzed for sperm count, motility, morphology (normal/abnormal and viability. Testes were also removed, weighed and processed for light microscopic studies.Results: The results showed that fertility were significantly decreased in addicted mice compared with control groups (P≤0.05. Epididymal sperm parameters and thickness of seminiferous epithelium were significantly decreased in experimental groups (dose-dependent compared with sham and control groups (P≤0.05. Gonadosomatic index was significantly reduced with high dose Kerack injected (70 mg/kg in comparison with control testes (P≤0.05.Conclusion: This study has shown the deleterious effects of Kerack used in addicted Iranian people on fertility for the first time. This effect is especially on epididymal sperm parameters in adult mice.

Albumin infusion after reperfusion prevents gut ischemia-reperfusion-induced gut-associated lymphoid tissue atrophy.

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Ikezawa, Fumie; Fukatsu, Kazuhiko; Moriya, Tomoyuki; Maeshima, Yoshinori; Okamoto, Koichi; Hara, Etsuko; Hiraide, Hoshio; Compher, Charlene W

2006-01-01

Our recent study clarified that gut ischemia-reperfusion (I/R) causes gut-associated lymphoid tissue (GALT) mass atrophy, a possible mechanism for increased morbidity of infectious complications after severe surgical insults. Because albumin administration reportedly reduces hemorrhagic shock-induced lung injury, we hypothesized that albumin treatment prevents GALT atrophy due to gut I/R. Male mice (n = 37) were randomized to albumin, normal saline, and sham groups. All groups underwent jugular vein catheter insertion. The albumin and normal saline groups underwent 75-minute occlusion of the superior mesenteric artery. During gut ischemia, all mice received normal saline infusions at 1.0 mL/h. The albumin group was given 5% bovine serum albumin in normal saline at 1.0 mL/h for 60 minutes after reperfusion, whereas the normal saline group received 0.9% sodium chloride at 1.0 mL/h. The sham group underwent laparotomy only. Mice were killed on day 1 or 7, and the entire small intestine was harvested. GALT lymphocytes were isolated and counted. Their phenotypes (alphabetaTCR, gammadeltaTCR, CD4, CD8, B220) were determined by flow cytometry. On day 1, the gut I/R groups showed significantly lower total lymphocyte and B cell numbers in Peyer's patches and the lamina propria than the sham group. However, the albumin infusion partially but significantly restored these cell numbers. On day 7, there were no significant differences in any of the parameters measured among the 3 groups. Albumin infusion after a gut ischemic insult may maintain gut immunity by preventing GALT atrophy.

Cardiovascular phenotype in Smad3 deficient mice with renovascular hypertension.

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Kashyap, Sonu; Warner, Gina; Hu, Zeng; Gao, Feng; Osman, Mazen; Al Saiegh, Yousif; Lien, Karen R; Nath, Karl; Grande, Joseph P

2017-01-01

Renovascular hypertension (RVH) has deleterious effects on both the kidney and the heart. TGF-β signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C) model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO) protects the stenotic kidney (STK) from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice. Renal artery stenosis (RAS) was established in Wild-type (WT) and Smad3 KO mice (129 genetic background) by placement of a polytetrafluoroethylene cuff on the right renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice, 1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice studied at 3 days following surgery showed extensive myocyte necrosis in KO but not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2 expression, macrophage influx, and increased MMP-9 activity. At later time points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or dissections were observed at any time point. Smad3 KO mice were backcrossed to the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days following surgery in 62.5% of mice; necropsy revealed aortic dissections as the cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the C57BL/6J background did not develop significant chronic renal damage. We conclude that the cardiovascular manifestations of Smad3 deficient mice are strain-specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice. Future studies will define mechanisms underlying this strain-specific effect on the cardiovascular system.

Cardiovascular phenotype in Smad3 deficient mice with renovascular hypertension.

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Sonu Kashyap

Full Text Available Renovascular hypertension (RVH has deleterious effects on both the kidney and the heart. TGF-β signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO protects the stenotic kidney (STK from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice. Renal artery stenosis (RAS was established in Wild-type (WT and Smad3 KO mice (129 genetic background by placement of a polytetrafluoroethylene cuff on the right renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice, 1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice studied at 3 days following surgery showed extensive myocyte necrosis in KO but not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2 expression, macrophage influx, and increased MMP-9 activity. At later time points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or dissections were observed at any time point. Smad3 KO mice were backcrossed to the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days following surgery in 62.5% of mice; necropsy revealed aortic dissections as the cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the C57BL/6J background did not develop significant chronic renal damage. We conclude that the cardiovascular manifestations of Smad3 deficient mice are strain-specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice. Future studies will define mechanisms underlying this strain-specific effect on the cardiovascular system.

Effectiveness of Traditional Chinese Acupuncture versus Sham Acupuncture: a Systematic Review

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Luís Carlos Lopes-Júnior

Full Text Available ABSTRACT Objective: to identify and synthesize the evidence from randomized clinical trials that tested the effectiveness of traditional Chinese acupuncture in relation to sham acupuncture for the treatment of hot flashes in menopausal women with breast cancer. Method: systematic review guided by the recommendations of the Cochrane Collaboration. Citations were searched in the following databases: MEDLINE via PubMed, Web of Science, CENTRAL, CINAHL, and LILACS. A combination of the following keywords was used: breast neoplasm, acupuncture, acupuncture therapy, acupuncture points, placebos, sham treatment, hot flashes, hot flushes, menopause, climacteric, and vasomotor symptoms. Results: a total of 272 studies were identified, five of which were selected and analyzed. Slight superiority of traditional acupuncture compared with sham acupuncture was observed; however, there were no strong statistical associations. Conclusions: the evidence gathered was not sufficient to affirm the effectiveness of traditional acupuncture compared with sham acupuncture.

Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice

DEFF Research Database (Denmark)

Bang, Christian A; Bro, Susanne; Bartels, Emil D

2007-01-01

Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild...... in cholic acid-fed sham mice. The results suggest that moderate uremia neither induces aortic inflammation nor atherosclerosis in C57BL/6J mice despite increased LDL/HDL cholesterol ratio and altered HDL composition....

On the physical nature and chemical utility of Kohn-Sham orbitals

International Nuclear Information System (INIS)

Baerends, E.J.

1996-01-01

Density functional calculations almost invariably use the one-electron Kohn-Sham orbitals to calculate the electron density. It is sometimes stated that these KS orbitals have no special physical meaning, but are constructs, arising in the KS formulation of DFT, that are only useful to obtain the density. We will argue that on the contrary the KS orbitals are often very similar to the molecular orbitals that arise in the Hartree-Fock model. When they differ the Kohn-Sham orbitals have certain advantageous properties and correspond in fact more closely to the orbitals used explicitly or implicitly in qualitative MO theory. The arguments of QMO theory, with their emphasis on bonding and antibonding nature of MOs, do hold perfectly for KS orbitals. The reason that Kohn-Sham orbitals are meaningful objects is related to the fact that the effective one-electron Kohn-Sham potential embodies the effects of electron correlation. It has recently become possible to calculate accurate Kohn-Sham potentials from accurate electron densities. This offers the possibility to study the structure of KS potentials (steps, peaks) and to relate this structure to electron correlation. More importantly, given exact Kohn-Sham potentials and orbitals it is possible to construct an exchange-correlation energy density that will, after integration over space, yield the exact exchange-correlation energy. It is possible to relate the local features of the exact energy density to aspects of electron correlation. The exact energy density may be used to judge existing model exchange-correlation energy densities and hopefully it will be helpful to devise improvements

Velocity form of the Kohn-Sham frequency-dependent polarizability equations

International Nuclear Information System (INIS)

Bartolotti, L.J.

1987-01-01

A single equation is derived for the determination of the first-order correction to the frequency-dependent density, due to the perturbation of a time-varying electric field. This new expression for the first-order correction to the frequency-dependent Kohn-Sham amplitudes depends explicitly upon the velocity form of the dipole-moment operator and the square of the Kohn-Sham Hamiltonian

Is sham cTBS real cTBS? The effect on EEG dynamics

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Alexander eOpitz

2015-01-01

Full Text Available Increasing sensitivity of modern evaluation tools allows for the study of weaker electric stimulation effects on neural populations. In the current study we examined the effects of sham continuous theta burst (cTBS transcranial magnetic stimulation to the left dorsolateral prefrontal cortex (DLPFC upon somatosensory evoked potentials (SEP and frontal-parietal phase coupling of alpha and beta bands. Sham TMS results in an induced electric field amplitude roughly 5% that of real TMS with a similar spatial extent in cortex. Both real and sham cTBS reduced the amplitude of the frontal P14-N30 SEP and increased local phase coupling in the alpha-beta frequency bands of left frontal cortex. In addition, both sham and real cTBS increased frontal-parietal phase coupling in the alpha-beta bands concomitant with an increase in amplitude of parietal P50-N70 complex. These data suggest that weak electric fields from sham cTBS can affect both local and downstream neuronal circuits, though in a different manner than high strength TMS.

Is sham cTBS real cTBS? The effect on EEG dynamics.

Science.gov (United States)

Opitz, Alexander; Legon, Wynn; Mueller, Jerel; Barbour, Aaron; Paulus, Walter; Tyler, William J

2014-01-01

Increasing sensitivity of modern evaluation tools allows for the study of weaker electric stimulation effects on neural populations. In the current study we examined the effects of sham continuous theta burst (cTBS) transcranial magnetic stimulation to the left dorsolateral prefrontal cortex (DLPFC) upon somatosensory evoked potentials (SEP) and frontal-parietal phase coupling of alpha and beta bands. Sham TMS results in an induced electric field amplitude roughly 5% that of real TMS with a similar spatial extent in cortex. Both real and sham cTBS reduced the amplitude of the frontal P14-N30 SEP and increased local phase coupling in the alpha-beta frequency bands of left frontal cortex. In addition, both sham and real cTBS increased frontal-parietal phase coupling in the alpha-beta bands concomitant with an increase in amplitude of parietal P50-N70 complex. These data suggest that weak electric fields from sham cTBS can affect both local and downstream neuronal circuits, though in a different manner than high strength TMS.

Co-inhibition of Angiotensin II Receptor and Endothelin-1 Attenuates Renal Injury in Unilateral Ureteral Obstructed Mice

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Yoon-Kyung Chang

2016-07-01

Full Text Available Background/Aims: Both endothelin-1 (ET-1 and the renin-angiotensin system (RAS may play important roles in renal fibrosis in the obstructed kidney. However, there have been few clear demonstrations of a relationship between their activation and additive or synergistic roles in renal fibrosis. We investigated the protective roles and relationship between renal RAS and ET-1 in unilateral ureteral obstruction (UUO mice. Methods: 8-week-old male C57BL/6 mice were divided into seven groups: sham, bosentan+sham, valsartan+sham, vehicle+UUO, bosentan+UUO, valsartan+UUO, and valsartan+bosentan+UUO. Valsartan and bosentan were administered orally using an NG tube (valsartan 10 mg/kg/day, bosentan 100 mg/kg/day for 8 days, after which the molecular and structural kidney parameters were evaluated. Bosentan treatment elevated plasma renin activity, renal renin, and AT1R expression in UUO mice. Results: Although valsartan decreased plasma ET-1 in these mice, it did not affect ET(A or ET(B in their kidneys. Co-treatment with valsartan and bosentan decreased ET-1 in these mice compared to the single treatments. Bosentan, but not valsartan, elevated eNOS expression in their kidneys. Co-treatment with valsartan and bosentan reduced TGF-β, α-SMA, and collagen IV expression, and the Masson's trichrome stained area in their kidneys. Conclusions: Bosentan and valsartan acted complementarily, and co-treatment with both drugs had an additive protective effect against renal fibrosis.

Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice.

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Junye Zhang

Full Text Available One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO to restore the secretory function of radiation-damaged salivary glands in mice.DFO (50 mg/kg/d was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy of submandibular glands. The total 55 mice were randomly divided into: (1 Normal group: mice received no treatment (n = 5; (2 Irradiation group (IR: mice only received irradiation (n = 5; (3 Pre-DFO group (D+IR (n = 10; (4 Pre+Post DFO group (D+IR+D (n = 10; (5 Post-DFO group (IR+D (n = 10; (6 For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5; sham2: Pre+Post sterilized water group (n = 5; sham3: Post-sterilized water group (n = 5. The salivary flow rate (SFR was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations.The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR.Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and more preserved stem cells.

Bypassing the Kohn-Sham equations with machine learning.

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Brockherde, Felix; Vogt, Leslie; Li, Li; Tuckerman, Mark E; Burke, Kieron; Müller, Klaus-Robert

2017-10-11

Last year, at least 30,000 scientific papers used the Kohn-Sham scheme of density functional theory to solve electronic structure problems in a wide variety of scientific fields. Machine learning holds the promise of learning the energy functional via examples, bypassing the need to solve the Kohn-Sham equations. This should yield substantial savings in computer time, allowing larger systems and/or longer time-scales to be tackled, but attempts to machine-learn this functional have been limited by the need to find its derivative. The present work overcomes this difficulty by directly learning the density-potential and energy-density maps for test systems and various molecules. We perform the first molecular dynamics simulation with a machine-learned density functional on malonaldehyde and are able to capture the intramolecular proton transfer process. Learning density models now allows the construction of accurate density functionals for realistic molecular systems.Machine learning allows electronic structure calculations to access larger system sizes and, in dynamical simulations, longer time scales. Here, the authors perform such a simulation using a machine-learned density functional that avoids direct solution of the Kohn-Sham equations.

Effect of electron radiation on aggressive behavior, activity, and hemopoiesis in mice

International Nuclear Information System (INIS)

Maier, D.M.; Landauer, M.R.; Davis, H.D.; Walden, T.L.

1989-01-01

The behavioral and physiological effects of 10 Gray (Gy) LINAC electrons in male Swiss-Webster mice were followed for 12 days postirradiation (PR). In Experiment 1, aggressive behavior was assessed in irradiated or sham-irradiated resident mice using a resident-intruder paradigm. Aggressive offensive behavior in the irradiated residents was significantly decreased beginning 2 to 5 days PR, and remained suppressed. Defensive behavior in the nonirradiated intruders was decreased significantly by day 5 PR. In Experiment 2, spontaneous locomotor activity was monitored. Ambulation of irradiated mice was significantly depressed from day 5 PR on, while rearing was affected as early as day 2 PR and remained suppressed. Body weights of irradiated animals were significantly decreased by 5 days PR. In Experiment 3, blood parameters were examined. Compared to sham-irradiated controls, leukocytes, erythrocytes, and hematocrit of irradiated mice were reduced significantly beginning on day 1 PR and remained suppressed, while platelets and hemoglobin were decreased beginning day 2 PR. These results demonstrate that 10 Gy of high-energy electrons results in earlier behavioral deficits than has been observed previously with the same dose of gamma photons. (author)

Sex-specific phenotypes of hyperthyroidism and hypothyroidism in mice.

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Rakov, Helena; Engels, Kathrin; Hönes, Georg Sebastian; Strucksberg, Karl-Heinz; Moeller, Lars Christian; Köhrle, Josef; Zwanziger, Denise; Führer, Dagmar

2016-01-01

Thyroid dysfunction is more common in the female population, however, the impact of sex on disease characteristics has rarely been addressed. Using a murine model, we asked whether sex has an influence on phenotypes, thyroid hormone status, and thyroid hormone tissue response in hyper- and hypothyroidism. Hypo- and hyperthyroidism were induced in 5-month-old female and male wildtype C57BL/6N mice, by LoI/MMI/ClO4 (-) or T4 i.p. treatment over 7 weeks, and control animals underwent sham treatment (N = 8 animals/sex/treatment). Animals were investigated for impact of sex on body weight, food and water intake, body temperature, heart rate, behaviour (locomotor activity, motor coordination, and strength), liver function, serum thyroid hormone status, and cellular TH effects on gene expression in brown adipose tissue, heart, and liver. Male and female mice showed significant differences in behavioural, functional, metabolic, biochemical, and molecular traits of hyper- and hypothyroidism. Hyperthyroidism resulted in increased locomotor activity in female mice but decreased muscle strength and motor coordination preferably in male animals. Hypothyroidism led to increased water intake in male but not female mice and significantly higher serum cholesterol in male mice. Natural sex differences in body temperature, body weight gain, food and water intake were preserved under hyperthyroid conditions. In contrast, natural sex differences in heart rate disappeared with TH excess and deprivation. The variations of hyper- or hypothyroid traits of male and female mice were not explained by classical T3/T4 serum state. TH serum concentrations were significantly increased in female mice under hyperthyroidism, but no sex differences were found under eu- or hypothyroid conditions. Interestingly, analysis of expression of TH target genes and TH transporters revealed little sex dependency in heart, while sex differences in target genes were present in liver and brown adipose tissue

17β-Estradiol administration promotes delayed cutaneous wound healing in 40-week ovariectomised female mice.

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Mukai, Kanae; Nakajima, Yukari; Urai, Tamae; Komatsu, Emi; Nasruddin; Sugama, Junko; Nakatani, Toshio

2016-10-01

This study investigated the effect of 17β-estradiol on wound healing in 40-week ovariectomised female mice. Thirty-six-week-old female mice were divided into three groups: medication with 17β-estradiol after ovariectomy (OVX + 17β-estradiol), ovariectomy (OVX) and sham (SHAM). The mice received two full-thickness wounds, and the OVX + 17β-estradiol group was administered 17β-estradiol at 0·01 g/day until healing. In the OVX + 17β-estradiol group, the ratio of wound area was significantly smaller than those of the OVX and SHAM groups on days 1-3, 5, 6, 8-12 and 9-12, respectively, the numbers of neutrophils and macrophages were significantly smaller than those on days 3 and 7, the ratio of re-epithelialisation was significantly higher than those on days 3 and 11, the ratio of myofibroblasts was significantly higher than those on day 11 and smaller on day 14, and the ratio of collagen fibres was significantly larger than that of the OVX group on days 7-14. We found that 17β-estradiol administration promotes cutaneous wound healing in 40-week female mice by reducing wound area, shortening inflammatory response, and promoting re-epithelialisation, collagen deposition and wound contraction. Our results suggest that cutaneous wound healing that is delayed because of ageing is promoted by exogenous and continuous 17β-estradiol administration. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Efficient construction of exchange and correlation potentials by inverting the Kohn-Sham equations.

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Kananenka, Alexei A; Kohut, Sviataslau V; Gaiduk, Alex P; Ryabinkin, Ilya G; Staroverov, Viktor N

2013-08-21

Given a set of canonical Kohn-Sham orbitals, orbital energies, and an external potential for a many-electron system, one can invert the Kohn-Sham equations in a single step to obtain the corresponding exchange-correlation potential, vXC(r). For orbitals and orbital energies that are solutions of the Kohn-Sham equations with a multiplicative vXC(r) this procedure recovers vXC(r) (in the basis set limit), but for eigenfunctions of a non-multiplicative one-electron operator it produces an orbital-averaged potential. In particular, substitution of Hartree-Fock orbitals and eigenvalues into the Kohn-Sham inversion formula is a fast way to compute the Slater potential. In the same way, we efficiently construct orbital-averaged exchange and correlation potentials for hybrid and kinetic-energy-density-dependent functionals. We also show how the Kohn-Sham inversion approach can be used to compute functional derivatives of explicit density functionals and to approximate functional derivatives of orbital-dependent functionals.

Restricted open-shell Kohn-Sham theory: N unpaired electrons

International Nuclear Information System (INIS)

Schulte, Marius; Frank, Irmgard

2010-01-01

Graphical abstract: High-spin or low-spin? The lowest-lying states for different multiplicities of iron complexes are described with a combination of restricted open-shell Kohn-Sham theory and Car-Parrinello molecular dynamics. - Abstract: We present an energy expression for restricted open-shell Kohn-Sham theory for N unpaired electrons. It is shown that it is possible to derive an explicit energy expression for all low-spin multiplets of systems that exhibit neither radial nor cylindrical symmetry. The approach was implemented in the CPMD code and tested for iron complexes.

Time-dependent density functional theory beyond Kohn-Sham Slater determinants.

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Fuks, Johanna I; Nielsen, Søren E B; Ruggenthaler, Michael; Maitra, Neepa T

2016-08-03

When running time-dependent density functional theory (TDDFT) calculations for real-time simulations of non-equilibrium dynamics, the user has a choice of initial Kohn-Sham state, and typically a Slater determinant is used. We explore the impact of this choice on the exchange-correlation potential when the physical system begins in a 50 : 50 superposition of the ground and first-excited state of the system. We investigate the possibility of judiciously choosing a Kohn-Sham initial state that minimizes errors when adiabatic functionals are used. We find that if the Kohn-Sham state is chosen to have a configuration matching the one that dominates the interacting state, this can be achieved for a finite time duration for some but not all such choices. When the Kohn-Sham system does not begin in a Slater determinant, we further argue that the conventional splitting of the exchange-correlation potential into exchange and correlation parts has limited value, and instead propose a decomposition into a "single-particle" contribution that we denote v, and a remainder. The single-particle contribution can be readily computed as an explicit orbital-functional, reduces to exchange in the Slater determinant case, and offers an alternative to the adiabatic approximation as a starting point for TDDFT approximations.

Analisis Kecenderungan Manhaj Akidah Shaykh Shams al-Din al-Sumatera’i

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MOHD HAIDHAR KAMARZAMAN

2016-12-01

Full Text Available Shaykh Shams al-Din al-Sumatera'i is a very great and respected scholar during 16th and 17th century of Acheh. His knowledge in various fields recognized by local and international scholars. He had been a Qadi Malik al-’Adil, a religious leader, who became a referred by communities and country during the reign of the three Sultans of Aceh. He has authored nearly 40 pieces of books related to the theology and sufism. This study focuses on the methods used by Shaykh Shams al-Din al-Sumatera'i in his theological writings. This study found that Shaykh Shams al-Din al-Sumatera'i had used six methods in the such writings.

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE-/- Mice With Unilateral Renal Artery Stenosis.

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Pathak, Alokkumar S; Huang, Jianhua; Rojas, Mauricio; Bazemore, Taylor C; Zhou, Ruihai; Stouffer, George A

2016-04-03

Chronic unilateral renal artery stenosis (RAS) causes accelerated atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice, but effects of restoration of renal blood flow on aortic atherosclerosis are unknown. Male ApoE(-/-) mice underwent sham surgery (n=16) or had partial ligation of the right renal artery (n=41) with the ligature being removed 4 days later (D4LR; n=6), 8 days later (D8LR; n=11), or left in place for 90 days (chronic RAS; n=24). Ligature removal at 4 or 8 days resulted in improved renal blood flow, decreased plasma angiotensin II levels, a return of systolic blood pressure to baseline, and increased plasma levels of neutrophil gelatinase associated lipocalin. Chronic RAS resulted in increased lipid staining in the aortic arch (33.2% [24.4, 47.5] vs 11.6% [6.1, 14.2]; Prenal blood flow at either 4 or 8 days after unilateral RAS had a beneficial effect on systolic blood pressure, aortic lipid deposition, and atheroma inflammation. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Idiopathic paraproteinemia. III. Increased frequency of paraproteinemia in thymectomized aging C57BL/KaLwRij and CBA/BrARij mice

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Radl, J.; Glopper, E. de; Berg, P. van den; Zwieten, M.J. van

1980-01-01

The influence of thymectomy on the appearance of idiopathic paraproteinemia (IP) during aging was investigated in mice of the C57BL/KaLwRij and CBA/BrARij strains, which under normal conditions develop IP in high and low frequency, respectively. Compared with sham-thymectomized mice, C57BL mice

Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation.

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Sakai, Mari; Suzuki, Tokiko; Tomita, Kengo; Yamashita, Shigeyuki; Palikhe, Sailesh; Hattori, Kohshi; Yoshimura, Naoki; Matsuda, Naoyuki; Hattori, Yuichi

2017-06-01

Dobutamine has been used in septic shock for many years as an only inotrope, but its benefit has been questioned. We weighed the effects of dobutamine and milrinone as inotropes in mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis. CLP-induced septic mice exhibited significant cardiac inflammation, as indicated by greatly increased mRNAs of proinflammatory cytokines and robust infiltration of inflammatory cells in the ventricular myocardium. Elevations of plasma cardiac troponin-I showed cardiac injury in CLP mice. Noninvasive echocardiographic assessment of cardiac function revealed that despite preserved left ventricular function in the presence of fluid replacement, the dobutamine inotropic response was significantly impaired in CLP mice compared with sham-operated controls. By contrast, milrinone exerted inotropic effects in sham-operated and CLP mice in an equally effective manner. Surface expression levels of β 1 -adrenoceptors and α-subunits of three main G protein families in the myocardium were unaffected by CLP-induced sepsis. Plasma cAMP levels were significantly elevated in both sham-operated and CLP mice in response to milrinone but only in sham-operated controls in response to dobutamine. Of phosphodiesterase (PDE) isoforms, PDE4D, but not PDE3A, both of which are responsible for cardiac cAMP hydrolysis, was significantly upregulated in CLP mouse myocardium. We define a novel mechanism for the impaired responsiveness to dobutamine as an inotrope in sepsis, and understanding the role of PDE4D in modulating cardiac functional responsiveness in sepsis may open the potential of a PDE4D-targeted therapeutic option in septic patients with low cardiac output who have a need for inotropic support. NEW & NOTEWORTHY Advisability of the usefulness of dobutamine in septic shock management is limited. Here, we reveal that the effect of dobutamine as a positive inotrope is impaired in mice with cecal ligation and puncture-induced sepsis

Magnetic Resonance Imaging Study Using True versus Sham Acupuncture

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Chunxiao Wu

2014-01-01

Full Text Available Functional magnetic resonance imaging (fMRI has been shown to detect the specificity of acupuncture points, as proved by numerous studies. In this study, resting-state fMRI was used to observe brain areas activated by acupuncture at the Taichong (LR3 acupoint. A total of 15 healthy subjects received brain resting-state fMRI before acupuncture and after sham and true acupuncture, respectively, at LR3. Image data processing was performed using Data Processing Assistant for Resting-State fMRI and REST software. The combination of amplitude of low-frequency fluctuation (ALFF and regional homogeneity (ReHo was used to analyze the changes in brain function during sham and true acupuncture. Acupuncture at LR3 can specifically activate or deactivate brain areas related to vision, movement, sensation, emotion, and analgesia. The specific alterations in the anterior cingulate gyrus, thalamus, and cerebellar posterior lobe have a crucial effect and provide a valuable reference. Sham acupuncture has a certain effect on psychological processes and does not affect brain areas related to function.

Histone Acetylation in Microglia Contributes to Exercise-Induced Hypoalgesia in Neuropathic Pain Model Mice.

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Kami, Katsuya; Taguchi, Satoru; Tajima, Fumihiro; Senba, Emiko

2016-05-01

Physical exercise can attenuate neuropathic pain (NPP), but the exact mechanism underlying exercise-induced hypoalgesia (EIH) remains unclear. Recent studies have shown that histone hyperacetylation via pharmacological inhibition of histone deacetylases in the spinal cord attenuates NPP, and that histone acetylation may lead to the production of analgesic factors including interleukin 10. We intended to clarify whether histone acetylation in microglia in the spinal dorsal horn contributes to EIH in NPP model mice. C57BL/6J mice underwent partial sciatic nerve ligation (PSL) and PSL- and sham-runner mice ran on a treadmill at a speed of 7 m/min for 60 min/d, 5 days per week, from 2 days after the surgery. PSL-sedentary mice developed mechanical allodynia and heat hyperalgesia, but such behaviors were significantly attenuated in PSL-runner mice. In immunofluorescence analysis, PSL surgery markedly increased the number of histone deacetylase 1-positive/CD11b-positive microglia in the ipsilateral superficial dorsal horn, and they were significantly decreased by treadmill-running. Moreover, the number of microglia with nuclear expression of acetylated H3K9 in the ipsilateral superficial dorsal horn was maintained at low levels in PSL-sedentary mice, but running exercise significantly increased them. Therefore, we conclude that the epigenetic modification that causes hyperacetylation of H3K9 in activated microglia may play a role in producing EIH. This article presents the importance of epigenetic modification in microglia in producing EIH. The current research is not only helpful for developing novel nonpharmacological therapy for NPP, but will also enhance our understanding of the mechanisms and availability of exercise in our daily life. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

The effectiveness of foot reflexology in inducing ovulation: a sham-controlled randomized trial.

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Holt, Jane; Lord, Jonathan; Acharya, Umesh; White, Adrian; O'Neill, Nyree; Shaw, Steve; Barton, Andy

2009-06-01

To determine whether foot reflexology, a complementary therapy, has an effect greater than sham reflexology on induction of ovulation. Sham-controlled randomized trial with patients and statistician blinded. Infertility clinic in Plymouth, United Kingdom. Forty-eight women attending the clinic with anovulation. Women were randomized to receive eight sessions of either genuine foot reflexology or sham reflexology with gentle massage over 10 weeks. The primary outcome was ovulation detected by serum progesterone level of >30 nmol/L during the study period. Twenty-six patients were randomized to genuine reflexology and 22 to sham (one randomized patient was withdrawn). Patients remained blinded throughout the trial. The rate of ovulation during true reflexology was 11 out of 26 (42%), and during sham reflexology it was 10 out of 22 (46%). Pregnancy rates were 4 out of 26 in the true group and 2 out of 22 in the control group. Because of recruitment difficulties, the required sample size of 104 women was not achieved. Patient blinding of reflexology studies is feasible. Although this study was too small to reach a definitive conclusion on the specific effect of foot reflexology, the results suggest that any effect on ovulation would not be clinically relevant. Sham reflexology may have a beneficial general effect, which this study was not designed to detect.

Excessive Vitamin E Intake Does Not Cause Bone Loss in Male or Ovariectomized Female Mice Fed Normal or High-Fat Diets.

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Ikegami, Hiroko; Kawawa, Rie; Ichi, Ikuyo; Ishikawa, Tomoko; Koike, Taisuke; Aoki, Yoshinori; Fujiwara, Yoko

2017-10-01

Background: Animal studies on the effects of vitamin E on bone health have yielded conflicting and inconclusive results, and to our knowledge, no studies have addressed the effect of vitamin E on bone in animals consuming a high-fat diet (HFD). Objective: This study aimed to evaluate the effect of excessive vitamin E on bone metabolism in normal male mice and ovariectomized female mice fed a normal diet (ND) or HFD. Methods: In the first 2 experiments, 7-wk-old male mice were fed an ND (16% energy from fat) containing 75 (control), 0 (vitamin E-free), or 1000 (high vitamin E) mg vitamin E/kg (experiment 1) or an HFD (46% energy from fat) containing 0, 200, 500, or 1000 mg vitamin E/kg (experiment 2) for 18 wk. In the third experiment, 7-wk-old sham-operated or ovariectomized female mice were fed the ND (75 mg vitamin E/kg) or HFD containing 0 or 1000 mg vitamin E/kg for 8 wk. At the end of the feeding period, blood and femurs were collected to measure bone turnover markers and analyze histology and microcomputed tomography. Results: In experiments 1 and 2, vitamin E intake had no effect on plasma alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activity, or bone formation, resorption, or volume in femurs in mice fed the ND or HFDs. In experiment 3, bone volume was significantly reduced (85%) in ovariectomized mice compared with that in sham-operated mice ( P vitamin E/kg. Conclusions: The results suggest that excess vitamin E intake does not cause bone loss in normal male mice or in ovariectomized or sham-operated female mice, regardless of dietary fat content. © 2017 American Society for Nutrition.

Methanol Extract of Euchelus asper Prevents Bone Resorption in Ovariectomised Mice Model

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Babita Balakrishnan

2014-01-01

Full Text Available Marine molluscs are widely distributed throughout the world and many bioactive compounds exhibiting antiviral, antitumor, antileukemic, and antibacterial activity have been reported worldwide. The present study was designed to investigate the beneficial effect of methanol extract of Euchelus asper (EAME on estrogen deficiency induced osteoporosis in ovariectomised mice model. Forty-two female Swiss albino mice were randomly assigned into Sham operated (Sham group and six ovariectomised (OVX subgroups such as OVX with vehicle (OVX; OVX with estradiol (2 mg/kg/day; OVX with EAME of graded doses (25, 50, 100, and 200 mg/kg/day. Bone turnover markers like serum alkaline phosphatase (ALP, serum acid phosphatase (ACP, serum calcium, and histological investigations of tibia and uterus were analysed. Metaphyseal DNA content of the femur bone was also studied. Antiosteoclastogenic activity of EAME was examined. Administration of EAME was able to reduce the increased bone turnover markers in the ovariectomised mice. Histomorphometric analysis revealed an increase in bone trabeculation and restoration of trabecular separation by EAME treatment. Metaphyseal DNA content of the femur of the OVX mice was increased by EAME administration. EAME also showed a potent antiosteoclastogenic behaviour. Thus, the present study reveals that EAME was able to successfully reduce the estrogen deficiency induced bone loss.

Cerebellar transcranial direct current stimulation in patients with ataxia: A double-blind, randomized, sham-controlled study.

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Benussi, Alberto; Koch, Giacomo; Cotelli, Maria; Padovani, Alessandro; Borroni, Barbara

2015-10-01

Numerous studies have highlighted the possibility of modulating the excitability of cerebellar circuits using transcranial direct current stimulation. The present study investigated whether a single session of cerebellar anodal transcranial direct current stimulation could improve symptoms in patients with ataxia. Nineteen patients with ataxia underwent a clinical and functional evaluation pre- and post-double-blind, randomized, sham, or anodal transcranial direct current stimulation. There was a significant interaction between treatment and time on the Scale for the Assessment and Rating of Ataxia, on the International Cooperative Ataxia Rating Scale, on the 9-Hole Peg Test, and on the 8-Meter Walking Time (P transcranial direct current stimulation can transiently improve symptoms in patients with ataxia and might represent a promising tool for future rehabilitative approaches. © 2015 International Parkinson and Movement Disorder Society.

Properties of Augmented Kohn-Sham Potential for Energy as Simple Sum of Orbital Energies.

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Zahariev, Federico; Levy, Mel

2017-01-12

A recent modification to the traditional Kohn-Sham method ( Levy , M. ; Zahariev , F. Phys. Rev. Lett. 2014 , 113 , 113002 ; Levy , M. ; Zahariev , F. Mol. Phys. 2016 , 114 , 1162 - 1164 ), which gives the ground-state energy as a direct sum of the occupied orbital energies, is discussed and its properties are numerically illustrated on representative atoms and ions. It is observed that current approximate density functionals tend to give surprisingly small errors for the highest occupied orbital energies that are obtained with the augmented potential. The appropriately shifted Kohn-Sham potential is the basic object within this direct-energy Kohn-Sham method and needs to be approximated. To facilitate approximations, several constraints to the augmented Kohn-Sham potential are presented.

[Application of locomotor activity test to evaluate functional injury after global cerebral ischemia in C57BL/6 mice].

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Zhang, Li-quan; Xu, Jia-ni; Wang, Zhen-zhen; Zeng, Li-jun; Ye, Yi-lu; Zhang, Wei-ping; Wei, Er-qing; Zhang, Qi

2014-05-01

To evaluate the application of locomotor activity test in functional injury after global cerebral ischemia (GCI) in C57BL/6 mice. GCI was induced by bilateral carotid arteries occlusion for 30 min in C57BL/6 mice. Mice were divided into sham group, GCI group and minocycline group. Saline or minocycline (45 mg/kg) was i.p. injected once daily for 6 d after ischemia. At Day 6 after ischemia, locomotor activity was recorded for 1 h in open field test. Total distance, central distance, central distance ratio, periphery distance, periphery distance ratio, central time and periphery time were used to evaluate the behavior characteristics of locomotor activity in C57BL/6 mice after ischemia. The survival neuron density was detected by Nissl staining in hippocampus, cortex and striatum. Compared with sham group, total distance, central distance and central time increased and periphery time decreased in C57BL/6 mice after GCI (PsLocomotor activity in open field test can objectively evaluate the behavior injury after GCI in mice. Central distance and central time can be used as indexes of quantitative assessment.

Effects of thyroid hormone analogue and a leukotrienes pathway-blocker on renal ischemia/reperfusion injury in mice

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Hadi Najah R

2011-12-01

Full Text Available Abstract Background Acute renal failure (ARF is an important clinical problem with a high mortality and morbidity. One of the primary causes of ARF is ischemia/reperfusion (I/R. Inflammatory process and oxidative stress are thought to be the major mechanisms causing I/R. MK-886 is a potent inhibitor of leukotrienes biosynthesis which may have anti-inflammatory and antioxidant effects through inhibition of polymorphonuclear leukocytes (PMNs infiltration into renal tissues. 3, 5-diiodothyropropionic acid (DITPA have evidences of improving effects on I/R in heart through modulation of cellular signaling in response to ischemic stress. The objective of present study was to assess the effects of MK-886 and DITPA on renal I/R injury. Methods A total of 24 Adult males of Swiss albino mice were randomized to four groups: I/R group (n = 6, mice underwent 30 minute bilateral renal ischemia and 48 hr reperfusion. Sham group (n = 6, mice underwent same anesthetic and surgical procedures except for ischemia induction. MK-886-treated group: (n = 6, I/R + MK-886 (6 mg/kg by intraperitoneal injection. DITPA-treated group: (n = 6, I/R + DITPA (3.75 mg/kg by intraperitoneal injection. After the end of reperfusion phase mice were sacrificed, blood samples were collected directly from the heart for determination of serum TNF-a, IL-6, urea and Creatinine. Both kidney were excised, the right one homogenized for oxidative stress parameters (MDA and GSH measurements and the left kidney fixed in formalin for histological examination. Results Serum TNF-α, IL-6, urea and Creatinine, kidney MDA levels and scores of histopathological changes were significantly (P 0.05 changes in levels of all study parameters as compared with that of I/R group. Conclusion The results of the present study show that MK-886 significantly ameliorated kidney damage that resulted from I/R. For DITPA, as its administration might not be successful, administration using a different protocol may

Configurational forces in electronic structure calculations using Kohn-Sham density functional theory

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Motamarri, Phani; Gavini, Vikram

2018-04-01

We derive the expressions for configurational forces in Kohn-Sham density functional theory, which correspond to the generalized variational force computed as the derivative of the Kohn-Sham energy functional with respect to the position of a material point x . These configurational forces that result from the inner variations of the Kohn-Sham energy functional provide a unified framework to compute atomic forces as well as stress tensor for geometry optimization. Importantly, owing to the variational nature of the formulation, these configurational forces inherently account for the Pulay corrections. The formulation presented in this work treats both pseudopotential and all-electron calculations in a single framework, and employs a local variational real-space formulation of Kohn-Sham density functional theory (DFT) expressed in terms of the nonorthogonal wave functions that is amenable to reduced-order scaling techniques. We demonstrate the accuracy and performance of the proposed configurational force approach on benchmark all-electron and pseudopotential calculations conducted using higher-order finite-element discretization. To this end, we examine the rates of convergence of the finite-element discretization in the computed forces and stresses for various materials systems, and, further, verify the accuracy from finite differencing the energy. Wherever applicable, we also compare the forces and stresses with those obtained from Kohn-Sham DFT calculations employing plane-wave basis (pseudopotential calculations) and Gaussian basis (all-electron calculations). Finally, we verify the accuracy of the forces on large materials systems involving a metallic aluminum nanocluster containing 666 atoms and an alkane chain containing 902 atoms, where the Kohn-Sham electronic ground state is computed using a reduced-order scaling subspace projection technique [P. Motamarri and V. Gavini, Phys. Rev. B 90, 115127 (2014), 10.1103/PhysRevB.90.115127].

Increase in cortical pyramidal cell excitability accompanies depression-like behavior in mice: a transcranial magnetic stimulation study.

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Sun, Peng; Wang, Furong; Wang, Li; Zhang, Yu; Yamamoto, Ryo; Sugai, Tokio; Zhang, Qing; Wang, Zhengda; Kato, Nobuo

2011-11-09

Clinical evidence suggests that cortical excitability is increased in depressives. We investigated its cellular basis in a mouse model of depression. In a modified version of forced swimming (FS), mice were initially forced to swim for 5 consecutive days and then were treated daily with repetitive transcranial magnetic stimulation (rTMS) or sham treatment for the following 4 weeks without swimming. On day 2 through day 5, the mice manifested depression-like behaviors. The next and last FS was performed 4 weeks later, which revealed a 4 week maintenance of depression-like behavior in the sham mice. In slices from the sham controls, excitability in cingulate cortex pyramidal cells was elevated in terms of membrane potential and frequencies of spikes evoked by current injection. Depolarized resting potential was shown to depend on suppression of large conductance calcium-activated potassium (BK) channels. This BK channel suppression was confirmed by measuring spike width, which depends on BK channels. Chronic rTMS treatment during the 4 week period significantly reduced the depression-like behavior. In slices obtained from the rTMS mice, normal excitability and BK channel activity were recovered. Expression of a scaffold protein Homer1a was reduced by the FS and reversed by rTMS in the cingulate cortex. Similar recovery in the same behavioral, electrophysiological, and biochemical features was observed after chronic imipramine treatment. The present study demonstrated that manifestation and disappearance of depression-like behavior are in parallel with increase and decrease in cortical neuronal excitability in mice and suggested that regulation of BK channels by Homer1a is involved in this parallelism.

Kaempferol attenuates acute lung injury in caecal ligation and puncture model of sepsis in mice.

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Rabha, Dipankar Jyoti; Singh, Thakur Uttam; Rungsung, Soya; Kumar, Tarun; Parida, Subhashree; Lingaraju, Madhu Cholenahalli; Paul, Avishek; Sahoo, Monalisa; Kumar, Dinesh

2018-03-01

Kaempferol is a flavonoid and important part of the diet. Kaempferol has shown antioxidant, antiinflammatory and antidiabetic activities in various studies. However, protective potential of kaempferol in acute lung injury induced by sepsis and its mechanism remains unclear. The present study was undertaken to evaluate the effect of kaempferol in sepsis-induced acute lung injury in mice and its possible mechanism of action. Acute lung injury was induced by CLP surgery in mice. Kaempferol (100 mg/kg bw) was administered orally one hour before caecal ligation and puncture surgery in mice. Mice were divided into four groups sham, KEM+sham, sepsis (CLP), and KEM+sepsis. Assessment of lung injury was done by estimation of protein content in lung tissue, lung edema, proinflammatory cytokines in plasma and lung tissue, oxidative stress, antioxidant enzymes, nitrite production, and histopathology. Kaempferol pretreated mice showed significant (P Kaempferol pretreatment showed reduction in cytokines IL-6, IL-1β, and TNF-α in plasma as well as in lung tissue in comparison with septic mice without pretreatment. Pretreatment with kaempferol did not show any reduction in MDA level in comparison with septic mice. Antioxidant enzymes SOD and catalase and nonenzymatic antioxidant GSH activities were also increased with kaempferol pretreatment in septic mice. Further, kaempferol pretreatment reduced the lung tissue nitrite level (P Kaempferol pretreatment did not decrease bacterial load in septic mice. Mice pretreated with kaempferol followed by sepsis showed lesser infiltration of cells and more arranged alveolar structure in histopathological analysis. The study suggests that kaempferol showed attenuation in sepsis-induced acute lung injury in mice through suppression of oxidative stress, iNOS, and ICAM-1 pathways.

High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice.

Science.gov (United States)

Bowen, T Scott; Eisenkolb, Sophia; Drobner, Juliane; Fischer, Tina; Werner, Sarah; Linke, Axel; Mangner, Norman; Schuler, Gerhard; Adams, Volker

2017-01-01

Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)-salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high-intensity interval training (HIIT). Sham-treated (n = 11), DOCA-salt-treated (n = 11), and DOCA-salt+HIIT-treated (n = 15) mice were studied over 4 wk. Diaphragm contractile function, protein expression, enzyme activity, and fiber cross-sectional area and type were subsequently determined. Elevated blood pressure confirmed hypertension in DOCA-salt mice independent of HIIT (P HIIT. Myosin heavy chain (MyHC) protein expression tended to decrease (∼30%; P = 0.06) in DOCA-salt vs. sham- and DOCA-salt+HIIT mice, whereas oxidative stress increased (P HIIT further prevented direct oxidant-mediated diaphragm contractile dysfunction (P hypertension induces diaphragm contractile dysfunction via an oxidant-mediated mechanism that is prevented by HIIT.-Bowen, T. S., Eisenkolb, S., Drobner, J., Fischer, T., Werner, S., Linke, A., Mangner, N., Schuler, G., Adams, V. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice. © FASEB.

Effect of low dose radiation on thymocyte cytosol and nuclei protein synthesis in mice

International Nuclear Information System (INIS)

Meng Qingyong; Chen Shali; Liu Shuzheng

2003-01-01

Objective: To the effect of low dose radiation on thymocyte cytosol and nuclei protein synthesis in mice. Methods: The expression of proteins was analyzed by gel filtration with Sephadex G-100 and HPLC based on separation of proteins on thymocyte cytosol and nuclei after whole-body irradiation with 75 mGy X-rays and sham-irradiation, and their biological activity was examined by mouse splenocyte proliferation and chromosome aberration of human peripheral blood lymphocytes. Results: HPLC analysis showed that there was a marked increase in expression of 61.4 kD protein in the extract of thymocyte cytosol and 30.4 kD protein in the extract of thymocyte nuclei in comparison with the corresponding fractions from the sham-irradiated control mice. These protein fractions from the thymocyte cytosol and nuclei of the irradiated mice showed both stimulating effect on normal T cell proliferation and protective effect on chromosome damage induced by high dose radiation. Conclusion: These findings might have implications in study of mechanism of immunoenhancement and cytogenetic adaptive response induced by low dose radiation

THE ETHICS OF SHAM SURGERY IN PARKINSON'S DISEASE: BACK TO THE FUTURE?

Science.gov (United States)

Swift, Teresa; Huxtable, Richard

2013-01-01

Despite intense academic debate in the recent past over the use of ‘sham surgery’ control groups in research, there has been a recent resurgence in their use in the field of neurodegenerative disease. Yet the primacy of ethical arguments in favour of sham surgery controls is not yet established. Preliminary empirical research shows an asymmetry between the views of neurosurgical researchers and patients on the subject, while different ethical guidelines and regulations support conflicting interpretations. Research ethics committees faced with a proposal involving sham surgery should be aware of its ethical complexities. An overview of recent and current placebo-controlled surgical trials in the field of Parkinson's Disease is provided here, followed by an analysis of the key ethical issues which such trials raise. PMID:22150772

Approximating the Shifted Hartree-Exchange-Correlation Potential in Direct Energy Kohn-Sham Theory.

Science.gov (United States)

Sharpe, Daniel J; Levy, Mel; Tozer, David J

2018-02-13

Levy and Zahariev [Phys. Rev. Lett. 113 113002 (2014)] have proposed a new approach for performing density functional theory calculations, termed direct energy Kohn-Sham (DEKS) theory. In this approach, the electronic energy equals the sum of orbital energies, obtained from Kohn-Sham-like orbital equations involving a shifted Hartree-exchange-correlation potential, which must be approximated. In the present study, density scaling homogeneity considerations are used to facilitate DEKS calculations on a series of atoms and molecules, leading to three nonlocal approximations to the shifted potential. The first two rely on preliminary Kohn-Sham calculations using a standard generalized gradient approximation (GGA) exchange-correlation functional and the results illustrate the benefit of describing the dominant Hartree component of the shift exactly. A uniform electron gas analysis is used to eliminate the need for these preliminary Kohn-Sham calculations, leading to a potential with an unconventional form that yields encouraging results, providing strong motivation for further research in DEKS theory.

Effects of 1.8 GHz radiofrequency field on microstructure and bone metabolism of femur in mice.

Science.gov (United States)

Guo, Ling; Zhang, Jun-Ping; Zhang, Ke-Ying; Wang, Huan-Bo; Wang, Huan; An, Guang-Zhou; Zhou, Yan; Meng, Guo-Lin; Ding, Gui-Rong

2018-04-30

To investigate the effects of 1.8 GHz radiofrequency (RF) field on bone microstructure and metabolism of femur in mice, C57BL/6 mice (male, age 4 weeks) were whole-body exposed or sham exposed to 1.8 GHz RF field. Specific absorption rates of whole body and bone were approximately 2.70 and 1.14 W/kg (6 h/day for 28 days). After exposure, microstructure and morphology of femur were observed by microcomputed tomography (micro-CT), Hematoxylin and Eosin (HE) and Masson staining. Subsequently, bone parameters were calculated directly from the reconstructed images, including structure model index, bone mineral density, trabecular bone volume/total volume, connectivity density, trabecular number, trabecular thickness, and trabecular separation. Biomarkers that reflect bone metabolism, such as serum total alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase 5b (TRACP-5b), were determined by biochemical assay methods. Micro-CT and histology results showed that there was no significant change in bone microstructure and the above parameters in RF group, compared with sham group. The activity of serum ALP and BALP increased 29.47% and 16.82%, respectively, in RF group, compared with sham group (P microstructure; however, it might promote metabolic function of osteoblasts in mice. Bioelectromagnetics. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

A Kohn-Sham system at zero temperature

DEFF Research Database (Denmark)

Cornean, Horia; Hoke, K.; Neidhardt, H.

2008-01-01

A one-dimensional Kohn-Sham system for spin particles is considered which effectively describes semiconductor nanostructures, and which is investigated at zero temperature. We prove the existence of solutions and derive a priori estimates. For this purpose we find estimates for eigenvalues...... by monotonicity arguments. Finally, we investigate the behavior of the system if the temperature approaches zero....

Strong Correlation in Kohn-Sham Density Functional Theory

NARCIS (Netherlands)

Malet, F.; Gori Giorgi, P.

2012-01-01

We use the exact strong-interaction limit of the Hohenberg-Kohn energy density functional to approximate the exchange-correlation energy of the restricted Kohn-Sham scheme. Our approximation corresponds to a highly nonlocal density functional whose functional derivative can be easily constructed,

Kohn-Sham potentials for fullerenes and spherical molecules

International Nuclear Information System (INIS)

Pavlyukh, Y.; Berakdar, J.

2010-01-01

We present a procedure for the construction of accurate Kohn-Sham potentials of quasispherical molecules starting from the first-principles valence densities. The method is demonstrated for the case of icosahedral C 20 2+ and C 60 molecules. Provided the density is N representable the Hohenberg-Kohn theorem guarantees the uniqueness of the obtained potentials. The potential is iteratively built following the suggestion of R. van Leeuwen and E. J. Baerends [Phys. Rev. A 49, 2421 (1994)]. The high symmetry of the molecules allows a parametrization of the angular dependence of the densities and the potentials using a small number of symmetry-adapted spherical harmonics. The radial behavior of these quantities is represented on a grid and the density is reconstructed from the approximate potential by numerically solving the coupled-channel Kohn-Sham equations. Subsequently, the potential is updated and the procedure is continued until convergence is achieved.

Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice.

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Mohamad Mokadem

Full Text Available Leptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastric bypass (RYGB induces weight loss that is substantial and sustained despite reducing plasma leptin levels. In addition, patients who fail to undergo diabetes remission after RYGB are hypoletinemic compared to those who do and to lean controls. We have previously demonstrated that the beneficial effects of RYGB in mice require the melanocortin-4 receptor, a downstream effector of leptin action. Based on these observations, we hypothesized that leptin is required for sustained weight reduction and improved glucose homeostasis observed after RYGB.To investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet.RYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance.

A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice.

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Motyl, Katherine J; Beauchemin, Megan; Barlow, Deborah; Le, Phuong T; Nagano, Kenichi; Treyball, Annika; Contractor, Anisha; Baron, Roland; Rosen, Clifford J; Houseknecht, Karen L

2017-10-01

Atypical antipsychotic (AA) drugs, including risperidone (RIS), are used to treat schizophrenia, bipolar disorder, and autism, and are prescribed off-label for other mental health issues. AA drugs are associated with severe metabolic side effects of obesity and type 2 diabetes. Cross-sectional and longitudinal data also show that risperidone causes bone loss and increases fracture risk in both men and women. There are several potential mechanisms of bone loss from RIS. One is hypogonadism due to hyperprolactinemia from dopamine receptor antagonism. However, many patients have normal prolactin levels; moreover we demonstrated that bone loss from RIS in mice can be blocked by inhibition of β-adrenergic receptor activation with propranolol, suggesting the sympathetic nervous system (SNS) plays a pathological role. Further, when, we treated ovariectomized (OVX) and sham operated mice daily for 8weeks with RIS or vehicle we demonstrated that RIS causes significant trabecular bone loss in both sham operated and OVX mice. RIS directly suppressed osteoblast number in both sham and OVX mice, but increased osteoclast number and surface in OVX mice alone, potentially accounting for the augmented bone loss. Thus, hypogonadism alone cannot explain RIS induced bone loss. In the current study, we show that dopamine and RIS are present in the bone marrow compartment and that RIS can exert its effects directly on bone cells via dopamine receptors. Our findings of both direct and indirect effects of AA drugs on bone are relevant for current and future clinical and translational studies investigating the mechanism of skeletal changes from AA drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

"I assumed that one was a placebo": exploring the consent process in a sham controlled acupressure trial.

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Hughes, John Gareth; Russell, Wanda; Breckons, Matthew; Richardson, Janet; Lloyd-Williams, Mari; Molassiotis, Alex

2014-10-01

In clinical trials where participants are likely to be able to distinguish between true and sham interventions, informing participants that they may receive a sham intervention increases the likelihood of participants 'breaking the blind' and invalidating trial findings. The present study explored participants' perceptions of the consent process in a sham controlled acupressure trial which did not explicitly indicate participants may receive a sham intervention. Nested qualitative study within a randomised sham controlled trial of acupressure wristbands for chemotherapy-related nausea. Convenience sample of 26 patients participated in semi-structured interviews. Interviews were audio-recorded and transcribed verbatim. Transcripts analysed thematically using framework analysis. Study conducted within three geographical sites in the UK: Manchester, Liverpool, and Plymouth. All participants indicated that they believed they were fully informed when providing written consent to participate in the trial. Participants' perceived it was acceptable to employ a sham intervention within the trial of acupressure wristbands without informing potential participants that they may receive a sham treatment. Despite the fact that participants were not informed that one of the treatment arms was a sham intervention the majority indicated they assumed one of the treatment arms would be placebo. Many trials of acupuncture and acupressure do not inform participants they may receive a sham intervention. The current study indicates patients' perceive this approach to the consent process as acceptable. However, the fact participants assume one treatment may be placebo threatens the methodological basis for utilising this approach to the consent process. Copyright © 2014 Elsevier Ltd. All rights reserved.

A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS).

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Rossi, Simone; Ferro, Marisa; Cincotta, Massimo; Ulivelli, Monica; Bartalini, Sabina; Miniussi, Carlo; Giovannelli, Fabio; Passero, Stefano

2007-03-01

There is growing interest in neuropsychiatry for repetitive transcranial magnetic stimulation (rTMS) as a neuromodulatory treatment. However, there are limitations in interpreting rTMS effects as a real consequence of physiological brain changes or as placebo-mediated unspecific effects, which may be particularly strong in psychiatric patients. This is due to the fact that existing sham rTMS procedures are less than optimal. A new placebo tool is introduced here, called real electro-magnetic placebo (REMP) device, which can simulate the scalp sensation induced by the real TMS, while leaving both the visual impact and acoustic sensation of real TMS unaltered. Physical, neurophysiological and behavioural variables of monophasic and biphasic single-pulse TMS and biphasic 1Hz and 20Hz rTMS procedures (at different intensities) were tested in subjects who were expert or naïve of TMS. Results of the real TMS were compared with those induced by the REMP device and with two other currently used sham procedures, namely the commercially available Magstim sham coil and tilting the real coil by 90 degrees . The REMP device, besides producing scalp sensations similar to the real TMS, attenuated the TMS-induced electric field (as measured by a dipole probe) to a biologically inactive level. Behaviourally, neither expert nor naïve TMS subjects identified the "coil at 90 degrees " or the "Magstim sham coil" as a real TMS intervention, whilst naïve subjects were significantly more likely to identify the REMP-attenuated TMS as real. The "goodness of sham" of the REMP device is demonstrated by physical, neurophysiological, and behavioural results. Such placebo TMS is superior to the available sham procedures when applied on subjects naïve to TMS, as in case of patients undergoing a clinical rTMS trial.

Poisson equation in the Kohn-Sham Coulomb problem

OpenAIRE

Manby, F. R.; Knowles, Peter James

2001-01-01

We apply the Poisson equation to the quantum mechanical Coulomb problem for many-particle systems. By introducing a suitable basis set, the two-electron Coulomb integrals become simple overlaps. This offers the possibility of very rapid linear-scaling treatment of the Coulomb contribution to Kohn-Sham theory.

Junk science for sale Sham journals proliferating online.

Science.gov (United States)

Klyce, Walter; Feller, Edward

2017-07-05

A new danger threatens the integrity of scholarly publishing: predatory journals. Internet-only, "open-access" publishing is a valid way for researchers to reach the public without a paywall separating them. But, of thousands of open-access scientific journals today, as many as twenty-five percent are believed to be fake, existing only to make money by charging authors high processing fees. In sham journals, peer review is cursory or absent: as many as eighty to ninety percent of submitted manuscripts are accepted, many within days, without any editorial comment. Predatory journalism can be remarkably good at mimicking reputable publishers. Sham journals use names and logos that closely resemble those of legitimate journals, intentionally confusing site visitors. Untrustworthy publications have not received the widespread, damning publicity they deserve. If junk science is not confronted and eliminated, it will continue to tarnish and undermine ethical, open-access scholarly publishing. [Full article available at http://rimed.org/rimedicaljournal-2017-07.asp].

High-intensity interval training beneficial effects on body mass, blood pressure, and oxidative stress in diet-induced obesity in ovariectomized mice.

Science.gov (United States)

Pimenta, Marcel; Bringhenti, Isabele; Souza-Mello, Vanessa; Dos Santos Mendes, Iara Karise; Aguila, Marcia B; Mandarim-de-Lacerda, Carlos A

2015-10-15

To investigate the possible beneficial effect of high-intensity interval training (HIIT) on skeletal muscle oxidative stress, body mass (BM) and systolic blood pressure (SBP) in ovariectomized mice fed or not fed a high-fat diet. Three-month-old female C57BL/6 mice were bilaterally ovariectomized (OVX group) or submitted to surgical stress without ovariectomy (SHAM group) and separated into standard chow (SHAM-SC; OVX-SC) and high-fat diet (SHAM-HF; OVX-HF) groups. After 13 weeks, an HIIT program (swimming) was carried out for 8 weeks in non-trained (NT) and trained (T) groups. The significant reduction of uterine mass and the cytological examination of vaginal smears in the OVX group confirmed that ovariectomy was successful. Before the HIIT protocol, the ovariectomized groups showed a greater BM than the SHAM group, irrespective of the diet they received. The HIIT minimized BM gain in animals fed an HF diet and/or ovariectomized. SBP and total cholesterol were increased in the OVX and HF animals compared to their counterparts, and the HIIT efficiently reduced these factors. In the HF and OVX mice, the muscular superoxide dismutase and catalase levels were low while their glutathione peroxidase and glutathione reductase levels were high and the HIIT normalized these parameters. Diet-induced obesity maximizes the deleterious effects of an ovariectomy. The HIIT protocol significantly reduced BM, SBP and oxidative stress in the skeletal muscle indicating that HIIT diminishes the cardiovascular and metabolic risk that is inherent to obesity and menopause. Copyright © 2015 Elsevier Inc. All rights reserved.

Kohn–Sham exchange-correlation potentials from second-order reduced density matrices

Energy Technology Data Exchange (ETDEWEB)

Cuevas-Saavedra, Rogelio; Staroverov, Viktor N., E-mail: vstarove@uwo.ca [Department of Chemistry, The University of Western Ontario, London, Ontario N6A 5B7 (Canada); Ayers, Paul W. [Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario L8S 4M1 (Canada)

2015-12-28

We describe a practical algorithm for constructing the Kohn–Sham exchange-correlation potential corresponding to a given second-order reduced density matrix. Unlike conventional Kohn–Sham inversion methods in which such potentials are extracted from ground-state electron densities, the proposed technique delivers unambiguous results in finite basis sets. The approach can also be used to separate approximately the exchange and correlation potentials for a many-electron system for which the reduced density matrix is known. The algorithm is implemented for configuration-interaction wave functions and its performance is illustrated with numerical examples.

Effects of nitric oxide inhibitors in mice with bladder outlet obstruction

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Marcy Lancia Pereira

Full Text Available ABSTRACT Purpose To investigate the lower urinary tract changes in mice treated with L-NAME, a non-selective competitive inhibitor of nitric oxide synthase (NOS, or aminoguanidine, a competitive inhibitor of inducible nitric oxide synthase (iNOS, after 5 weeks of partial bladder outlet obstruction (BOO, in order to evaluate the role of constitutive and non-constitutive NOS in the pathogenesis of this experimental condition. Materials and Methods C57BL6 male mice were partially obstructed and randomly allocated into 6 groups: Sham, Sham + L-NAME, Sham + aminoguanidine, BOO, BOO + L-NAME and BOO + aminoguanidine. After 5 weeks, bladder weight was obtained and cystometry and tissue bath contractile studies were performed. Results BOO animals showed increase of non-voiding contractions (NVC and bladder capacity, and also less contractile response to Carbachol and Electric Field Stimulation. Inhibition of NOS isoforms improved bladder capacity and compliance in BOO animals. L-NAME caused more NVC, prevented bladder weight gain and leaded to augmented contractile responses at muscarinic and electric stimulation. Aminoguanidine diminished NVC, but did not avoid bladder weight gain in BOO animals and did not improve contractile responses. Conclusion It can be hypothesized that chronic inhibition of three NOS isoforms in BOO animals leaded to worsening of bladder function, while selective inhibition of iNOS did not improve responses, what suggests that, in BOO animals, alterations are related to constitutive NOS.

Chronic nicotine differentially alters spontaneous recovery of contextual fear in male and female mice.

Science.gov (United States)

Tumolo, Jessica M; Kutlu, Munir Gunes; Gould, Thomas J

2018-04-02

Post-traumatic stress disorder (PTSD) is a devastating disorder with symptoms such as flashbacks, hyperarousal, and avoidance of reminders of the traumatic event. Exposure therapy, which attempts to extinguish fear responses, is a commonly used treatment for PTSD but relapse following successful exposure therapy is a frequent problem. In rodents, spontaneous recovery (SR), where extinguished fear responses resurface following extinction treatment, is used as a model of fear relapse. Previous studies from our lab showed that chronic nicotine impaired fear extinction and acute nicotine enhanced SR of contextual fear in adult male mice. In addition, we showed that acute nicotine's effects were specific to SR as acute nicotine did not affect recall of contextual fear conditioning in the absence of extinction. However, effects of chronic nicotine administration on SR are not known. Therefore, in the present study, we investigated if chronic nicotine administration altered SR or recall of contextual fear in adult male and female C57BL/6J mice. Our results showed that chronic nicotine significantly enhanced SR in female mice and significantly decreased SR in males. Chronic nicotine had no effect on recall of contextual fear in males or females. Female sham mice also had significantly less baseline SR than male sham mice. Overall, these results demonstrate sex differences in SR of fear memories and that chronic nicotine modulates these effects on SR but nicotine does not alter recall of contextual fear. Copyright © 2018 Elsevier B.V. All rights reserved.

Delayed radiation injury of gut-exposed and gut-shielded mice. II. The decrement in life span

International Nuclear Information System (INIS)

Spalding, J.F.; Archuleta, R.F.; Prine, J.R.

1978-01-01

Two mouse strains (RF/J and C57B1/6J) were exposed to x-ray doses totaling 400, 800, and 1200 rad. Total doses were given in 200-rad fractions at 7-day intervals to the whole body, gut only, or bone tissue with the gut shielded. Animals were anesthetized during exposure. Two control groups were used. A sham control group was anesthetized but not exposed to x rays, and another control group received neither anesthesia nor x-radiation. All mice were retained in a standard laboratory environment for observations on life span and histopathology at death. Life shortening was observed in all irradiated groups of strain RF/J mice and was attributed primarily to an increase in incidence and/or earlier onset of neoplasia. Life shortening was observed in the C57B1/6J whole-body exposed mice, but the effect appeared to be noncarcinogenic. Shielding of the bone or gut tissue proved to have a 100% sparing effect in strain C57 mice and none in strain RF mice. In both mouse strains, the sham control groups (anesthetized but not irradiated) showed approximately 8% life shortening below the non-anesthetized control groups and increased incidences of neoplasia of approximately 40%, suggesting that sodium pentabarbital may be as carcinogenic as x-radiation

Mechanism of suppressive effect of low dose radiation on cancer cell dissemination in mice

International Nuclear Information System (INIS)

Fu Haiqing; Li Xiuyi; Chen Yubing; Zhang Yingchun; Liu Shuzheng

1997-01-01

Influence of low dose radiation on immunity in C57 BL/6 mice injected with cancer cells was studied. In mice given 75 mGy WBI 24 h before injection of Lewis lung carcinoma cells or B 16 melanoma cells, the percentage of S-phase thymocytes and CD 3+ thymocytes, the splenic NK cell activity, IL-2 secretion and γIFN secretion were found to be potentiated 2∼8 day after irradiation in comparison with the sham-irradiation mice. The results suggest that low dose radiation might suppress cancer cell dissemination via the enhancement of immune reactivity

Local-scaling transformations and the direct determination of Kohn--Sham orbitals and potentials for beryllium

International Nuclear Information System (INIS)

Ludena, E.V.; Maldonado, J.; Lopez-Boada, R.; Koga, T.; Kryachko, E.S.

1995-01-01

Local-scaling transformations are used in the present work to obtain accurate Kohn--Sham 1s and 2s orbitals for the beryllium atom by means of a density-constrained variation of the single-determinant kinetic energy functional. An analytic representation of these Kohn--Sham orbitals is given and the quality of the different types of orbitals generated is discussed with particular reference to their kinetic energy and momenta mean values. In addition, we determine the effective Kohn--Sham potential and analyze it in terms of its exchange-only and correlation contributions

Imaging the functional connectivity of the Periaqueductal Gray during genuine and sham electroacupuncture treatment

Directory of Open Access Journals (Sweden)

Tu Peichi

2010-11-01

Full Text Available Abstract Background Electroacupuncture (EA is currently one of the most popular acupuncture modalities. However, the continuous stimulation characteristic of EA treatment presents challenges to the use of conventional functional Magnetic Resonance Imaging (fMRI approaches for the investigation of neural mechanisms mediating treatment response because of the requirement for brief and intermittent stimuli in event related or block designed task paradigms. A relatively new analysis method, functional connectivity fMRI (fcMRI, has great potential for studying continuous treatment modalities such as EA. In a previous study, we found that, compared with sham acupuncture, EA can significantly reduce Periaqueductal Gray (PAG activity when subsequently evoked by experimental pain. Given the PAG's important role in mediating acupuncture analgesia, in this study we investigated functional connectivity with the area of the PAG we previously identified and how that connectivity was affected by genuine and sham EA. Results Forty-eight subjects, who were randomly assigned to receive either genuine or sham EA paired with either a high or low expectancy manipulation, completed the study. Direct comparison of each treatment mode's functional connectivity revealed: significantly greater connectivity between the PAG, left posterior cingulate cortex (PCC, and precuneus for the contrast of genuine minus sham; significantly greater connectivity between the PAG and right anterior insula for the contrast of sham minus genuine; no significant differences in connectivity between different contrasts of the two expectancy levels. Conclusions Our findings indicate the intrinsic functional connectivity changes among key brain regions in the pain matrix and default mode network during genuine EA compared with sham EA. We speculate that continuous genuine EA stimulation can modify the coupling of spontaneous activity in brain regions that play a role in modulating pain

Interplay between Endometriosis and Pregnancy in a Mouse Model.

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Mariela Andrea Bilotas

Full Text Available To evaluate the effect of endometriosis on fertility and the levels of the IL-2 and IFN-γ in the peritoneal fluid in a mouse model; to evaluate the effect of pregnancy on endometriotic lesion growth, apoptosis and cell proliferation.Two month old C57BL/6 female mice underwent either a surgical procedure to induce endometriosis or a sham surgery. Four weeks after surgery mice were mated and sacrificed at day 18 of pregnancy. Number of implantation sites, fetuses and fetal weight were recorded. Endometriotic lesions were counted, measured, excised and fixed. Apoptosis and cell proliferation were evaluated in lesions by TUNEL and immunohistochemistry for PCNA respectively. Levels of IL-2 and IFN-γ were assessed by ELISA in the peritoneal fluid.Pregnancy rate (i.e. pregnant mice/N decreased in mice with endometriosis. However there were no significant differences in resorption rate, litter size and pup weight between groups. IFN-γ augmented in endometriosis mice independently of pregnancy outcome. Additionally IFN-γ increased in pregnant endometriosis mice compared to pregnant sham animals. While IFN-γ increased in non pregnant versus pregnant mice in the sham group, IL-2 was increased in non pregnant mice in the endometriosis group. The size of endometriotic lesions increased in pregnant mice while apoptosis increased in the stroma and cell proliferation decreased in the epithelium of these lesions. Additionally, leukocyte infiltration, necrosis and decidualization were increased in the same lesions.Pregnancy rate is reduced in this mouse model of endometriosis. Levels of IL-2 are increased in the peritoneal fluid of mice with endometriosis suggesting a role of this cytokine in infertility related to this disease. The size of endometriotic lesions is increased in pregnant mice; however pregnancy has a beneficial effect on lesions by decreasing cell proliferation and by increasing apoptosis, decidualization and necrosis.

Interplay between Endometriosis and Pregnancy in a Mouse Model.

Science.gov (United States)

Bilotas, Mariela Andrea; Olivares, Carla Noemí; Ricci, Analía Gabriela; Baston, Juan Ignacio; Bengochea, Tatiana Soledad; Meresman, Gabriela Fabiana; Barañao, Rosa Inés

2015-01-01

To evaluate the effect of endometriosis on fertility and the levels of the IL-2 and IFN-γ in the peritoneal fluid in a mouse model; to evaluate the effect of pregnancy on endometriotic lesion growth, apoptosis and cell proliferation. Two month old C57BL/6 female mice underwent either a surgical procedure to induce endometriosis or a sham surgery. Four weeks after surgery mice were mated and sacrificed at day 18 of pregnancy. Number of implantation sites, fetuses and fetal weight were recorded. Endometriotic lesions were counted, measured, excised and fixed. Apoptosis and cell proliferation were evaluated in lesions by TUNEL and immunohistochemistry for PCNA respectively. Levels of IL-2 and IFN-γ were assessed by ELISA in the peritoneal fluid. Pregnancy rate (i.e. pregnant mice/N) decreased in mice with endometriosis. However there were no significant differences in resorption rate, litter size and pup weight between groups. IFN-γ augmented in endometriosis mice independently of pregnancy outcome. Additionally IFN-γ increased in pregnant endometriosis mice compared to pregnant sham animals. While IFN-γ increased in non pregnant versus pregnant mice in the sham group, IL-2 was increased in non pregnant mice in the endometriosis group. The size of endometriotic lesions increased in pregnant mice while apoptosis increased in the stroma and cell proliferation decreased in the epithelium of these lesions. Additionally, leukocyte infiltration, necrosis and decidualization were increased in the same lesions. Pregnancy rate is reduced in this mouse model of endometriosis. Levels of IL-2 are increased in the peritoneal fluid of mice with endometriosis suggesting a role of this cytokine in infertility related to this disease. The size of endometriotic lesions is increased in pregnant mice; however pregnancy has a beneficial effect on lesions by decreasing cell proliferation and by increasing apoptosis, decidualization and necrosis.

EZH2 Inhibition Ameliorates Transverse Aortic Constriction-Induced Pulmonary Arterial Hypertension in Mice

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Zhan-Li Shi

2018-01-01

Full Text Available Background. EPZ005687 is a selective inhibiter of methyltransferase EZH2. In this article, we investigated the protective role and mechanism of EPZ005687 in transverse aortic constriction-induced pulmonary arterial hypertension in mice. Methods. We assigned 15 (6–8 weeks old male balb/c mice to 3 groups randomly: Sham control + DMSO group, TAC + DMSO group, and TAC + EPZ005687 group (10 mg kg−1, once a week for 4 weeks. On day 28 following TAC operation, the right ventricular systolic blood pressure (RVSBP was measured, and lung tissues were collected for laboratory examinations (DHE, Western blot, real-time PCR, and ChIP. Results. Murine PAH model was successfully created by TAC operation as evidenced by increased RVSBP and hypertrophic right ventricle. Compared with the sham control, TAC-induced PAH markedly upregulated the expression of EZH2 and ROS deposition in lungs in PAH mice. The inhibiter of methyltransferase EZH2, EPZ005687 significantly inhibits the development of TAC-induced PAH in an EZH2-SOD1-ROS dependent manner. Conclusion. Our data identified that EZH2 serves a fundamental role in TAC-induced PAH, and administration of EPZ005687 might represent a novel therapeutic target for the treatment of TAC-induced PAH.

Role of the spleen in cyclophosphamide-induced hematosuppression and extramedullary hematopoiesis in mice.

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Wang, Yuli; Meng, Qinggang; Qiao, Haiquan; Jiang, Hongchi; Sun, Xueying

2009-05-01

Extramedullary hematopoiesis (EMH) is induced in spleens due to various diseases. The aim of this study is to investigate the role of spleen in cyclophosphamide (CTX)-induced hematosuppression and EMH in mice. Balb/c mice were IP injected with 300 mg/kg CTX 2 weeks after splenectomy or sham operation and randomly sacrificed 1, 3, 7, 14, and 21 days after injection. Blood samples were collected, and spleens were weighed, histologically analyzed, and then used for flow cytometry. There were significant differences in white blood count, red blood count, platelet numbers and hemoglobin concentration between the splenectomized and sham-operated mice after CTX injection. The cellularity of the spleen was reduced 3 days following CTX treatment but then rose 7 days after CTX treatment. The numbers of colony-forming units in the spleen reached a peak 7 days after CTX injection, then declined. Flow cytometry demonstrated the percentage of CD34(+) and CD117(+) cells in the spleen increased 7 days after CTX injection, indicating the hematopoietic stem and progenitor cells in the spleen. The study indicates that EMH occurs as a compensatory reaction to CTX-induced hematosuppression in the murine spleen, implying that conservation of the spleen may promote the recovery of cancer patients from chemotherapy-induced hematosuppression.

Effects of leptin treatment and Western diet on wheel running in selectively bred high runner mice.

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Meek, Thomas H; Dlugosz, Elizabeth M; Vu, Kim T; Garland, Theodore

2012-05-15

The role of leptin in regulating physical activity is varied. The behavioral effects of leptin signaling depend on the type of activity and the animal's physiological state. We used mice from lines selectively bred for high voluntary wheel running to further study how leptin regulates volitional exercise. Mice from four replicate high runner (HR) lines typically run ~3-fold more revolutions per day than those from four non-selected control (C) lines. HR mice have altered dopamine function and differences from C in brain regions known to be important in leptin-mediated behavior. Furthermore, male HR mice have been found to dramatically increase running when administered Western diet, an effect possibly mediated through leptin signaling. Male mice from generation 61 (representing three HR lines and one C line) were allowed wheel access at 24 days of age and given either Western diet (high in fat and with added sucrose) or standard chow. After four weeks, Western diet significantly increased circulating leptin, insulin, C-peptide, gastric inhibitory polypeptide, and inflammatory hormone resistin concentrations in HR mice (C mice not measured). Western diet increased running in HR mice, but did not significantly affect running in C mice. During the fifth week, all mice received two days of intra-peritoneal sham injections (physiological saline) followed by three days of murine recombinant leptin injections, and then another six days of sham injections. Leptin treatment significantly decreased caloric intake (adjusted for body mass) and body mass in all groups. Wheel running significantly increased with leptin injections in HR mice (fed Western or standard diet), but was unaffected in C mice. Whether Western diet and leptin treatment stimulate wheel running in HR mice through the same physiological pathways awaits future study. These results have implications for understanding the neural and endocrine systems that control locomotor activity, food consumption, and body

ELSI: A unified software interface for Kohn-Sham electronic structure solvers

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Yu, Victor Wen-zhe; Corsetti, Fabiano; García, Alberto; Huhn, William P.; Jacquelin, Mathias; Jia, Weile; Lange, Björn; Lin, Lin; Lu, Jianfeng; Mi, Wenhui; Seifitokaldani, Ali; Vázquez-Mayagoitia, Álvaro; Yang, Chao; Yang, Haizhao; Blum, Volker

2018-01-01

Solving the electronic structure from a generalized or standard eigenproblem is often the bottleneck in large scale calculations based on Kohn-Sham density-functional theory. This problem must be addressed by essentially all current electronic structure codes, based on similar matrix expressions, and by high-performance computation. We here present a unified software interface, ELSI, to access different strategies that address the Kohn-Sham eigenvalue problem. Currently supported algorithms include the dense generalized eigensolver library ELPA, the orbital minimization method implemented in libOMM, and the pole expansion and selected inversion (PEXSI) approach with lower computational complexity for semilocal density functionals. The ELSI interface aims to simplify the implementation and optimal use of the different strategies, by offering (a) a unified software framework designed for the electronic structure solvers in Kohn-Sham density-functional theory; (b) reasonable default parameters for a chosen solver; (c) automatic conversion between input and internal working matrix formats, and in the future (d) recommendation of the optimal solver depending on the specific problem. Comparative benchmarks are shown for system sizes up to 11,520 atoms (172,800 basis functions) on distributed memory supercomputing architectures.

Time-dependent internal density functional theory formalism and Kohn-Sham scheme for self-bound systems

International Nuclear Information System (INIS)

Messud, Jeremie

2009-01-01

The stationary internal density functional theory (DFT) formalism and Kohn-Sham scheme are generalized to the time-dependent case. It is proven that, in the time-dependent case, the internal properties of a self-bound system (such as an atomic nuclei or a helium droplet) are all defined by the internal one-body density and the initial state. A time-dependent internal Kohn-Sham scheme is set up as a practical way to compute the internal density. The main difference from the traditional DFT formalism and Kohn-Sham scheme is the inclusion of the center-of-mass correlations in the functional.

The ethics of sham surgery on research subjects with cognitive impairments that affect decision-making capacity.

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Resnik, David B; Miller, Frank

2010-09-01

Populations recruited to participate in sham surgery clinical trials sometimes include patients with cognitive impairments that affect decision-making capacity. In this commentary we examine arguments for and against including these patients in sham surgery clinical trials. We argue that patients with cognitive impairments that affect decision-making capacity should not be excluded from a sham surgery clinical trial if there are scientific reasons for including them in the study and basic ethical requirements for clinical research are met. Published by Elsevier Inc.

Effects of short-term swimming exercise on bone mineral density, geometry, and microstructural properties in sham and ovariectomized rats

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Foong Kiew Ooi

2014-12-01

Full Text Available Little information exists about the effects of swimming exercise on bone health in ovariectomized animals with estrogen deficiency, which resembles the postmenopausal state and age-related bone loss in humans. This study investigated the effects of swimming exercise on tibia and femur bone mineral density (BMD, geometry, and microstructure in sham and ovariectomized rats. Forty 3-month-old female rats were divided into four groups: sham operated-sedentary control (Sham-control, sham operated with swimming exercise group (Sham-Swim, ovariectomy-sedentary control (OVx-control, and ovariectomy and swimming exercise (OVx-Swim groups. Swimming sessions were performed by the rats 90 minutes/day for 5 days/week for a total of 8 weeks. At the end of the study, tibial and femoral proximal volumetric total BMD, midshaft cortical volumetric BMD, cross-sectional area, and cross-sectional moment of inertia (MOI, and bone microstructural properties were measured for comparison. Data were analyzed using one-way analysis of variance (ANOVA. The Sham-Swim group exhibited significantly (p < 0.05; one-way ANOVA greater values in bone geometry parameters, that is, tibial midshaft cortical area and MOI compared to the Sham-control group. However, no significant differences were observed in these parameters between the Ovx-Swim and Ovx-control groups. There were no significant differences in femoral BMD between the Sham-Swim and Sham-control groups. Nevertheless, the Ovx-Swim group elicited significantly (p < 0.05; one-way ANOVA higher femoral proximal total BMD and improved bone microstructure compared to the Ovx-Sham group. In conclusion, the positive effects of swimming on bone properties in the ovariectomized rats in the present study may suggest that swimming as a non- or low-weight-bearing exercise may be beneficial for enhancing bone health in the postmenopausal population.

Spinal SIRT1 activation attenuates neuropathic pain in mice.

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Haijun Shao

Full Text Available Abnormal histone acetylation occurs during neuropathic pain through an epigenetic mechanism. Silent information regulator 1 (sir2 or SIRT1, a NAD-dependent deacetylase, plays complex systemic roles in a variety of processes through deacetylating acetylated histone and other specific substrates. But the role of SIRT1 in neuropathic pain is not well established yet. The present study was intended to detect SIRT1 content and activity, nicotinamide (NAM and nicotinamide adenine dinucleotide (NAD in the spinal cord using immunoblotting or mass spectroscopy over time in mice following chronic constriction injury (CCI or sham surgery. In addition, the effect of intrathecal injection of NAD or resveratrol on thermal hyperalgesia and mechanical allodynia was evaluated in CCI mice. Finally, we investigated whether SIRT1 inhibitor EX-527 could reverse the anti-nociceptive effect of NAD or resveratrol. It was found that spinal SIRT1 expression, deacetylase activity and NAD/NAM decreased significantly 1, 3, 7, 14 and 21 days after CCI surgery as compared with sham group. In addition, daily intrathecal injection of 5 µl 800 mM NAD 1 h before and 1 day after CCI surgery or single intrathecal injection of 5 µl 90 mM resveratrol 1 h before CCI surgery produced a transient inhibitory effect on thermal hyperalgesia and mechanical allodynia in CCI mice. Finally, an intrathecal injection of 5 µl 1.2 mM EX-527 1 h before NAD or resveratrol administration reversed the anti-nociceptive effect of NAD or resveratrol. These data indicate that the reduction in SIRT1 deacetylase activity may be a factor contributing to the development of neuropathic pain in CCI mice. Our findings suggest that the enhancement of spinal NAD/NAM and/or SIRT1 activity may be a potentially promising strategy for the prevention or treatment of neuropathic pain.

A selective cannabinoid CB2 agonist attenuates damage and improves memory retention following stroke in mice.

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Ronca, Richard D; Myers, Alyssa M; Ganea, Doina; Tuma, Ronald F; Walker, Ellen A; Ward, Sara Jane

2015-10-01

We have recently demonstrated that treatment with a cannabinoid CB2 agonist was protective in a mouse middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. The present study aimed to determine whether these protective effects of CB2 agonism would extend to a mouse photoinjury model of permanent ischemia and determine associated alterations in cognition and infarct size. Mice received three injections of the CB2 selective agonist O-1966 or vehicle 1h prior to and 2 and 5days following induction of stroke. Infarct size was assessed at 1, 3, or 7days post-injury and learning and memory effects of injury and O-1966 treatment were assessed on days 6 and 7 using a novel object recognition task and an operant acquisition and retention procedure. O-1966 treated mice had significantly smaller infarct volumes compared with vehicle treated mice. Photoinjury was also associated with a significant memory impairment on day 7 post-injury, and this deficit was reversed with O-1966 treatment. Surprisingly, sham-operated mice receiving O-1966 treatment showed a significant learning deficit in both the recognition and operant tasks compared with vehicle treated sham mice. We conclude that CB2 activation is protective against cognitive deficits and tissue damage following permanent ischemia, but may dysregulate glial or neuronal function of learning and memory circuits in the absence of injury and/or inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Mitigating cutaneous sensation differences during tDCS: comparing sham versus low intensity control conditions.

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Brunyé, Tad T; Cantelon, Julie; Holmes, Amanda; Taylor, Holly A; Mahoney, Caroline R

2014-01-01

Cutaneous sensations at electrode sites during the administration of direct current brain stimulation may inadvertently influence participants' subjective experience and task performance. The present study evaluated the utility of a methodological variation that substitutes sham administration with very low intensity (0.5 mA) current delivery. We used a 4 × 1 high-definition ring electrode transcranial direct current (HD-tDCS) system to target the left dorsolateral prefrontal cortex (Brodmann's Area 9). Four stimulation conditions were compared in a repeated-measures design: sham 2.0 mA and 0.5 mA intensity, versus active 2.0 mA and 0.5 mA intensity. During stimulation participants performed a cognitive interference task that activates the cingulo-frontal-parietal network, and periodically provided perceived sensation ratings. We demonstrate that a relatively low intensity control condition attenuates otherwise large differences in perceived sensation between active and sham conditions. Critically, behavioral task differences maintained between the two active conditions. A low intensity control stimulation condition may prove a viable methodological alternative to conventional sham techniques used in repeated-measures designs, though important limitations are discussed. Published by Elsevier Inc.

Effects of ovariectomy and exercise training intensity on energy substrate and hepatic lipid metabolism, and spontaneous physical activity in mice.

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Tuazon, Marc A; Campbell, Sara C; Klein, Dylan J; Shapses, Sue A; Anacker, Keith R; Anthony, Tracy G; Uzumcu, Mehmet; Henderson, Gregory C

2018-06-01

Menopause is associated with fatty liver, glucose dysregulation, increased body fat, and impaired bone quality. Previously, it was demonstrated that single sessions of high-intensity interval exercise (HIIE) are more effective than distance- and duration-matched continuous exercise (CE) on altering hepatic triglyceride (TG) metabolism and very-low density lipoprotein-TG (VLDL-TG) secretion. Six weeks training using these modalities was examined for effects on hepatic TG metabolism/secretion, glucose tolerance, body composition, and bone mineral density (BMD) in ovariectomized (OVX) and sham-operated (SHAM) mice. OVX and SHAM were assigned to distance- and duration-matched CE and HIIE, or sedentary control. Energy expenditure during exercise was confirmed to be identical between CE and HIIE and both similarly reduced post-exercise absolute carbohydrate oxidation and spontaneous physical activity (SPA). OVX vs. SHAM displayed impaired glucose tolerance and greater body fat despite lower hepatic TG, and these outcomes were not affected by training. Only HIIE increased hepatic AMPK in OVX and SHAM, but neither training type impacted VLDL-TG secretion. As expected, BMD was lower in OVX, and training did not affect long bones. The results reveal intensity-dependent effects on hepatic AMPK expression and general exercise effects on subsequent SPA and substrate oxidation that is independent of estrogen status. These findings support the notion that HIIE can impact aspects of liver physiology in females while the effects of exercise on whole body substrate selection appear to be independent of training intensity. However, neither exercise approach mitigated the impairment in glucose tolerance and elevated body fat occurring in OVX mice. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of adiponectin deficiency on intestinal damage and hematopoietic responses of mice exposed to gamma radiation

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Ponemone, Venkatesh; Fayad, Raja; Gove, Melissa E.; Pini, Maria [Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612 (United States); Fantuzzi, Giamila, E-mail: giamila@uic.edu [Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612 (United States)

2010-08-07

Adiponectin (APN) is an adipose tissue-derived cytokine that regulates insulin sensitivity and inflammation. It is also involved in modulation of cell proliferation by binding to various growth factors. Based on its known effects in modulating cell proliferation and oxidative stress, APN may potentially be involved in regulating tissue damage and repair following irradiation. Adiponectin KO mice and their WT littermates were exposed to a single whole-body dose of 3 or 6 Gy gamma radiation. Radiation-induced alterations were studied in jejunum, blood, bone marrow and thymus at days 1 and 5 post-irradiation and compared with sham-irradiated groups. In WT mice, irradiation did not significantly alter serum APN levels while inducing a significant decrease in serum leptin. Irradiation caused a significant reduction in thymocyte cellularity, with concomitant decrease in CD4{sup +}, CD8{sup +} and CD4{sup +}CD8{sup +} T cell populations, with no significant differences between WT and APN KO mice. Irradiation resulted in a significantly higher increase in the frequency of micronucleated reticulocytes in the blood of APN KO compared with WT mice, whereas frequency of micronucleated normochromatic erythrocytes in the bone marrow at day 5 was significantly higher in WT compared with APN KO mice. Finally, irradiation induced similar alterations in villus height and crypt cell proliferation in the jejunum of WT and APN KO mice. Jejunum explants from sham-irradiated APN KO mice produced higher levels of IL-6 compared with tissue from WT animals, but the difference was no longer apparent following irradiation. Our data indicate that APN deficiency does not play a significant role in modulating radiation-induced gastrointestinal injury in mice, while it may participate in regulation of damage to the hematopoietic system.

Effect of adiponectin deficiency on intestinal damage and hematopoietic responses of mice exposed to gamma radiation

International Nuclear Information System (INIS)

Ponemone, Venkatesh; Fayad, Raja; Gove, Melissa E.; Pini, Maria; Fantuzzi, Giamila

2010-01-01

Adiponectin (APN) is an adipose tissue-derived cytokine that regulates insulin sensitivity and inflammation. It is also involved in modulation of cell proliferation by binding to various growth factors. Based on its known effects in modulating cell proliferation and oxidative stress, APN may potentially be involved in regulating tissue damage and repair following irradiation. Adiponectin KO mice and their WT littermates were exposed to a single whole-body dose of 3 or 6 Gy gamma radiation. Radiation-induced alterations were studied in jejunum, blood, bone marrow and thymus at days 1 and 5 post-irradiation and compared with sham-irradiated groups. In WT mice, irradiation did not significantly alter serum APN levels while inducing a significant decrease in serum leptin. Irradiation caused a significant reduction in thymocyte cellularity, with concomitant decrease in CD4 + , CD8 + and CD4 + CD8 + T cell populations, with no significant differences between WT and APN KO mice. Irradiation resulted in a significantly higher increase in the frequency of micronucleated reticulocytes in the blood of APN KO compared with WT mice, whereas frequency of micronucleated normochromatic erythrocytes in the bone marrow at day 5 was significantly higher in WT compared with APN KO mice. Finally, irradiation induced similar alterations in villus height and crypt cell proliferation in the jejunum of WT and APN KO mice. Jejunum explants from sham-irradiated APN KO mice produced higher levels of IL-6 compared with tissue from WT animals, but the difference was no longer apparent following irradiation. Our data indicate that APN deficiency does not play a significant role in modulating radiation-induced gastrointestinal injury in mice, while it may participate in regulation of damage to the hematopoietic system.

Different effects of scopolamine on learning, memory, and nitric oxide metabolite levels in hippocampal tissues of ovariectomized and Sham-operated rats

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Hamid Azizi-Malekabadi

2012-06-01

Full Text Available Different effects of scopolamine on learning, memory, and nitric oxide (NO metabolites in hippocampal tissues of ovariectomized (OVX and sham-operated rats were investigated. The animals in the Sham-Scopolamine (Sham-Sco and OVX-Scopolamine (OVX-Sco Groups were treated with 2 mg/kg scopolamine before undergoing the Morris water maze, while the animals in the Sham and OVX Groups received saline. The time latency and path length were significantly higher in both the Sham-Sco and the OVX-Sco Groups, in comparison with the Sham and OVX Groups, respectively (p<0.001. Significantly lower NO metabolite levels in the hippocampi of the Sham-Sco Group were observed, compared with the Sham Group (p<0.001, while there was no significant difference between the OVX-Sco and OVX Groups. The decreased NO level in the hippocampus may play a role in the learning and memory deficits induced by scopolamine. However, it seems that the effect of scopolamine on hippocampal NO differs between situations of presence and absence of ovarian hormones.

Temperature-Controlled Delivery of Radiofrequency Energy in Fecal Incontinence: A Randomized Sham-Controlled Clinical Trial.

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Visscher, Arjan P; Lam, Tze J; Meurs-Szojda, Maria M; Felt-Bersma, Richelle J F

2017-08-01

Controlled delivery of radiofrequency energy has been suggested as treatment for fecal incontinence. The aim of this study was to determine whether the clinical response to the radiofrequency energy procedure is superior to sham in patients with fecal incontinence. This was a randomized sham-controlled clinical trial from 2008 to 2015. This study was conducted in an outpatient clinic. Forty patients with fecal incontinence in whom maximal conservative management had failed were randomly assigned to receiving either radiofrequency energy or sham procedure. Fecal incontinence was measured using the Vaizey incontinence score (range, 0-24). The impact of fecal incontinence on quality of life was measured by using the fecal incontinence quality-of-life score (range, 1-4). Measurements were performed at baseline and at 6 months. Anorectal function was evaluated using anal manometry and anorectal endosonography at baseline and at 3 months. At baseline, Vaizey incontinence score was 16.8 (SD 2.9). At t = 6 months, the radiofrequency energy group improved by 2.5 points on the Vaizey incontinence score compared with the sham group (13.2 (SD 3.1), 15.6 (SD 3.3), p = 0.02). The fecal incontinence quality-of-life score at t = 6 months was not statistically different. Anorectal function did not show any alteration. Patients with severe fecal incontinence were included in the study, thus making it difficult to generalize the results. Both radiofrequency energy and sham procedure improved the fecal incontinence score, the radiofrequency energy procedure more than sham. Although statistically significant, the clinical impact for most of the patients was negligible. Therefore, the radiofrequency energy procedure should not be recommended for patients with fecal incontinence until patient-related factors associated with treatment success are known. See Video Abstract at http://links.lww.com/DCR/A373.

Radon inhalation suppresses nephropathy in streptozotocin-induced type-1 diabetic mice

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Nishiyama, Yuichi; Kataoka, Takahiro; Yamato, Keiko; Etani, Reo; Taguchi, Takehito; Yamaoka, Kiyonori

2016-01-01

In this study, we investigated the suppressive effects of radon inhalation against nephropathy in C57BL/6J mice with type-1 diabetes induced by intraperitoneal injection of streptozotocin (50 mg/kg weight, given five times). Four weeks after diabetes induction, the diabetic mice were continuously treated with inhaled radon-222 of 2000 Bq/m3 or air only (sham) for four weeks. The results showed that radon inhalation did not affect type-1 diabetic symptoms such as body weight loss, hyperglycemia, and hypoinsulinemia. However, diabetic mice treated with radon showed lower urinary albumin excretion and fibrotic change in renal glomeruli compared with diabetic mice not treated with radon. Furthermore, renal superoxide dismutase activity and glutathione content were significantly higher in diabetic mice treated with radon than in diabetic mice not treated with radon. These findings suggested that radon inhalation enhanced renal antioxidants activities, resulting in the suppression of diabetic nephropathy. This study may contribute to the development of a novel approach in the treatment of nephropathy for diabetic patients. (author)

Protective effects of ulinastatin on cardiac dysfunction in mice with heat stroke and its mechanism

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Jing-jing JI

2017-06-01

Full Text Available Objective To examine the effects of ulinastatin (UTI on cardiac dysfunction in mice with heat stroke and its possible mechanism. Methods 20 mice were divided into four groups randomly: room temperature plus normal saline (Sham+NS, room temperature plus UTI (Sham+UTI, heat stress plus normal saline (HS+NS, heat stress plus UTI (HS+UTI, 5 each. 105U/kg UTI was delivered by intraperitoneal injection before the onset of the heat stress. Room temperature groups were housed at room temperature (23.0±0.5℃, while heat stress groups were kept in an incubator at 36.5±0.5℃ and humidity of 65.0%±2.0%. The rectal temperature (Tr reaching 42℃ was taken as severe heat stroke, and the time in two heat stress groups was recorded. The mice were transferred to the room temperature (23.0±0.5℃ for natural cooling after the heat stroke onset. 6 hours after the treatment, cardiac output (CO was ultrasonographically detected, the myocardium was separated for histopathological examination and the expression of total p38 and phosphorylated p38 (p-p38 was determined by Western blotting. Results The time to reach 42℃ in HS+UTI group was significantly prolonged (P=0.044. Compared with the Sham+NS group, the CO in HS+NS and HS+UTI group decreased significantly (P=0.017, and the score of myocardial inflammation (P<0.001 and p-p38/p38 ratio (P<0.001 increased. The CO was significantly higher in HS+UTI group than in HS+NS group (P=0.030, and the score of myocardial inflammation (P<0.001 and p-p38/p38 ratio (P=0.001 were significantly lower. Conclusion Ulinastatin might improve the cardiac function in mice with heat stroke by decreasing the p-p38 and alleviating the inflammation response. DOI: 10.11855/j.issn.0577-7402.2017.04.04

The effects of green tea extract on teratogenicity induced by low frequency electromagnetic field on bone marrow Balb/C mice embryo

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Baharara Javad

2014-01-01

Full Text Available Introduction: Electromagnetic fields produce free radicals which might be teratogen. Camellia sinensis is rich in natural antioxidants and antioxidants can neutralize free radicals effects. In present research the effect of C. sinensis extract in reduction of teratogenicity induced by electromagnetic field with 50 gauss intensity was studied on bone marrow of Balb/C mice fetuses. Methods: In this experimental study, 24 Balb/C pregnant mice were randomly divided into four groups: control, sham exposed (off position, experimental 1 (electromagnetic field with 50-gauss intensity and experimental 2 (treatment by C. sinensis extract + electromagnetic field with 50-gauss intensity. After treatment period, the bone marrow aspirates of Balb/C mice embryos were prepared and studied by Giemsa. The quantitative data were analyzed by Kruskal-Wallis and Kolmogorov- Smirnov using SPSS16 software at the level of p<0.05. Results: The mean number of promyelocytes, myelocytes, erythrocytes, necrotic and apoptotic cells in experimental group1 compared with sham exposed embryos showed significant increase but the mean number of eosinophils in experimental group 1 compared with sham exposed embryos showed significant decrease. The mean number of promyelocyte and erythrocyte in experimental group 2 compared with experimental group 1 showed significant decrease. The mean of necrotic and apoptotic cells, in experimental group 2 compared with experimental group 1 showed significant increase. Conclusion: Usage of C. sinensis can decrease the damage due to teratogenicity induced by low frequency electromagnetic field in some cells.

Effect of Cell Phone Radiation (940 MHz on the Learning and Memory of Balb/c mice

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J Baharara

2009-07-01

After behavioral studies, fetal heads were collected, fixed in 10% paraformaldehyde and paraffine embedded. Results: Microwave-exposed mice were slower than sham-exposed, and cage control in swim speed (WM. Error Analyses rates reveal significant exposure effect in RAM and MWM. However, in this study the exposed group had not significantly lost their hippocampal CA3 neurons comparing to controls or sham exposed group. Conclusion: Increased time to locate a submerged in water maze, reference memory (entries into unbaited arms, working memory (repeated entries into baited arms, show that acute exposure to pulsed microwaves caused a deficit in spatial reference memory in the mouse. Keywords: Mobile phone, learning, memory, hippocampus

Sham-controlled, randomized, feasibility trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma

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Meng, Zhiqiang; Garcia, M. Kay; Hu, Chaosu; Chiang, Joseph; Chambers, Mark; Rosenthal, David I.; Peng, Huiting; Wu, Caijun; Zhao, Qi; Zhao, Genming; Liu, Luming; Spelman, Amy; Palmer, J. Lynn; Wei, Qi; Cohen, Lorenzo

2013-01-01

Background Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients. Quality of life (QOL) is impaired, and available treatments are of little benefit. This trial determined the feasibility of conducting a sham-controlled trial of acupuncture and whether acupuncture could prevent xerostomia among head/neck patients undergoing radiotherapy. Methods A sham controlled, feasibility trial was conducted at Fudan University Shanghai Cancer Center, Shanghai, China among patients with nasopharyngeal carcinoma undergoing radiotherapy. To determine feasibility of a sham procedure, 23 patients were randomized to real acupuncture (N = 11) or to sham acupuncture (N = 12). Patients were treated 3 times/week during their course of radiotherapy. Subjective measures were the Xerostomia Questionnaire (XQ) and MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN). Objective measures were unstimulated whole salivary flow rates (UWSFR) and stimulated salivary flow rates (SSFR). Patients were followed for 1 month after radiotherapy. Results XQ scores for acupuncture were significantly lower than sham controls starting in week 3 and lasted through the 1-month follow-up (all P’s xerostomia symptoms and improved QOL when compared with sham acupuncture. Large-scale, multi-center, randomized, placebo-controlled trials are now needed. PMID:22285177

In vivo preclinical low field MRI monitoring of tumor growth following a suicide gene therapy in an ortho-topic mice model of human glioblastoma

International Nuclear Information System (INIS)

Breton, E.; Goetz, Ch.; Aubertin, G.; Constantinesco, A.; Choquet, Ph.; Kintz, J.; Accart, N.; Grellier, B.; Erbs, Ph.; Rooke, R.

2010-01-01

Purpose The aim of this study was to monitor in vivo with low field MRI growth of a murine ortho-topic glioma model following a suicide gene therapy. Methods The gene therapy consisted in the stereotactic injection in the mice brain of a modified vaccinia virus Ankara (M.V.A.) vector encoding for a suicide gene (FCU1) that transforms a non toxic pro-drug 5-fluoro-cytosine (5-F.C.) to its highly cytotoxic derivatives 5-fluorouracil (5-F.U.) and 5-fluoro-uridine-5 monophosphate (5-F.U.M.P.). Using a warmed-up imaging cell, sequential 3D T1 and T2 0.1T MRI brain examinations were performed on 16 Swiss female nu/nu mice bearing ortho-topic human glioblastoma (U 87-MG cells). The 6-week in vivo MRI follow-up consisted in a weekly measurement of the intracerebral tumor volume leading to a total of 65 examinations. Mice were divided in four groups: sham group (n = 4), sham group treated with 5-F.C. only (n = 4), sham group with injection of M.V.A.-FCU1 vector only (n = 4), therapy group administered with M.V.A.-FCU1 vector and 5-F.C. (n = 4). Measurements of tumor volumes were obtained after manual segmentation of T1- and T2-weighted images. Results Intra-observer and inter-observer tumor volume measurements show no significant differences. No differences were found between T1 and T2 volume tumor doubling times between the three sham groups. A significant statistical difference (p < 0.05) in T1 and T2 volume tumor doubling times between the three sham groups and the animals treated with the intratumoral injection of M.V.A.-FCU1 vector in combination with 2 weeks per os 5-F.C. administration was demonstrated. Conclusion Preclinical low field MRI was able to monitor efficacy of suicide gene therapy in delaying the tumor growth in an in vivo mouse model of ortho-topic glioblastoma. (authors)

Impacts of Bone Marrow Stem Cells on Caspase-3 Levels after Spinal Cord Injury in Mice

Directory of Open Access Journals (Sweden)

Noushin Gashmardi

2017-11-01

Full Text Available Spinal cord injury (SCI is a drastic disability that leads to spinal cord impairment. This study sought to determine the effects of bone marrow stem cells (BMSCs on caspase-3 levels after acute SCI in mice. Forty-two mice were randomly divided into 3 groups: control (2 subcategories, subjected to no intervention; sham (3 subcategories, subjected to acute SCI; and experimental (2 subcategories, subjected to SCI and cell transplantation. In the experimental group, 2×105 BMSCs were injected intravenously 1 day after SCI. The mesenchymal property of the cells was assessed. The animals in the 3 groups were sacrificed 1, 21, and 35 days after the induction of injury and caspase-3 levels were evaluated using a caspase-3 assay kit. The obtained values were analyzed with ANOVA and Tukey tests using GraphPad and SPSS. Based on the assessments, the transplanted cells were spindle-shaped and were negative for the hematopoietic markers of CD34 and CD45 and positive for the expression of the mesenchymal marker of CD90 and osteogenic induction. The caspase-3 levels showed a significant increase in the sham and experimental groups in comparison to the control group. One day after SCI, the caspase-3 level was significantly higher in the sham group (1.157±0.117 than in the other groups (P<0.000. Twenty-one days after SCI, the caspase-3 level was significantly lower in the experimental group than in the sham group (0.4±0.095 vs. 0.793±0.076; P˂0.000. Thirty-five days following SCI, the caspase-3 level was lower in the experimental group than in the sham group (0.223±0.027 vs. 0.643±0.058; P˂0.000. We conclude that BMSC transplantation was able to downregulate the caspase-3 level after acute SCI, underscoring the role of caspase-3 as a marker for the assessment of treatment efficacy in acute SCI.

Statistical electron angular correlation coefficients for atoms within the Hohenberg-Kohn-Sham theory

International Nuclear Information System (INIS)

Pathak, R.K.

1985-01-01

Statistical electron angular correlation coefficients tau = 2 2 He through 14 Si, within the Hohenberg-Kohn-Sham density-functional formalism. These are computed with use of the spectral sum rules obtained from the pseudoexcitation spectrum employing the recent formulation of the time-dependent Kohn-Sham theory due to Bartolotti. Various approximations to the exchange-correlation energy functional are used and for first-row atoms, a comparison is made with the highly accurate correlation coefficients recently obtained by Thakkar. The present tau values show closer agreement with those of Thakkar with increasing number of electrons

A spectral scheme for Kohn-Sham density functional theory of clusters

Science.gov (United States)

Banerjee, Amartya S.; Elliott, Ryan S.; James, Richard D.

2015-04-01

Starting from the observation that one of the most successful methods for solving the Kohn-Sham equations for periodic systems - the plane-wave method - is a spectral method based on eigenfunction expansion, we formulate a spectral method designed towards solving the Kohn-Sham equations for clusters. This allows for efficient calculation of the electronic structure of clusters (and molecules) with high accuracy and systematic convergence properties without the need for any artificial periodicity. The basis functions in this method form a complete orthonormal set and are expressible in terms of spherical harmonics and spherical Bessel functions. Computation of the occupied eigenstates of the discretized Kohn-Sham Hamiltonian is carried out using a combination of preconditioned block eigensolvers and Chebyshev polynomial filter accelerated subspace iterations. Several algorithmic and computational aspects of the method, including computation of the electrostatics terms and parallelization are discussed. We have implemented these methods and algorithms into an efficient and reliable package called ClusterES (Cluster Electronic Structure). A variety of benchmark calculations employing local and non-local pseudopotentials are carried out using our package and the results are compared to the literature. Convergence properties of the basis set are discussed through numerical examples. Computations involving large systems that contain thousands of electrons are demonstrated to highlight the efficacy of our methodology. The use of our method to study clusters with arbitrary point group symmetries is briefly discussed.

Sortilin 1 Loss-of-Function Protects Against Cholestatic Liver Injury by Attenuating Hepatic Bile Acid Accumulation in Bile Duct Ligated Mice.

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Li, Jibiao; Woolbright, Benjamin L; Zhao, Wen; Wang, Yifeng; Matye, David; Hagenbuch, Bruno; Jaeschke, Hartmut; Li, Tiangang

2018-01-01

Sortilin 1 (Sort1) is an intracellular trafficking receptor that mediates protein sorting in the endocytic or secretory pathways. Recent studies revealed a role of Sort1 in the regulation of cholesterol and bile acid (BA) metabolism. This study further investigated the role of Sort1 in modulating BA detoxification and cholestatic liver injury in bile duct ligated mice. We found that Sort1 knockout (KO) mice had attenuated liver injury 24 h after bile duct ligation (BDL), which was mainly attributed to less bile infarct formation. Sham-operated Sort1 KO mice had about 20% larger BA pool size than sham-operated wildtype (WT) mice, but 24 h after BDL Sort1 KO mice had significantly attenuated hepatic BA accumulation and smaller BA pool size. After 14 days BDL, Sort1 KO mice showed significantly lower hepatic BA concentration and reduced expression of inflammatory and fibrotic marker genes, but similar degree of liver fibrosis compared with WT mice. Unbiased quantitative proteomics revealed that Sort1 KO mice had increased hepatic BA sulfotransferase 2A1, but unaltered phase-I BA metabolizing cytochrome P450s or phase-III BA efflux transporters. Consistently, Sort1 KO mice showed elevated plasma sulfated taurocholate after BDL. Finally, we found that liver Sort1 was repressed after BDL, which may be due to BA activation of farnesoid x receptor. In conclusion, we report a role of Sort1 in the regulation of hepatic BA detoxification and cholestatic liver injury in mice. The mechanisms underlying increased hepatic BA elimination in Sort1 KO mice after BDL require further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Retention and egg production of Microphallus pygmaeus in mice: the influence of the adrenal cortex.

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Ahmad, R A; James, B L; Kamis, A B

1986-01-01

Fewer adult Microphallus pygmaeus are recovered from the small intestine of adrenalectomized male mice than from sham-operated counterparts. Preinfection intraperitoneal injection of 2 IU or 4 IU ACTH daily for 7 days increases the initial primary worm burden in male mice. Preinfection intramuscular injection of 325 micrograms corticosterone daily for 7 days increases the initial worm burden and alters the subsequent rate of decline and duration of the primary infection. However, egg production is unaffected. The changes in parasite numbers are attributed to the immunosuppressive action of corticosterone.

Oral lactoferrin protects against experimental candidiasis in mice.

Science.gov (United States)

Velliyagounder, K; Alsaedi, W; Alabdulmohsen, W; Markowitz, K; Fine, D H

2015-01-01

To determine the role of human lactoferrin (hLF) in protecting the oral cavities of mice against Candida albicans infection in lactoferrin knockout (LFKO(-/-)) mice was compared to wild-type (WT) mice. We also aim to determine the protective role of hLF in LFKO(-/-) mice. Antibiotic-treated immunosuppressed mice were inoculated with C. albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7 days of infection. To determine the protective role of hLF, we added 0·3% solution of hLF to the drinking water given to some of the mice. CFU count, scoring of lesions and microscopic observations were carried out to determine the severity of infection. LFKO(-/-) I mice showed a 2 log (P = 0·001) higher CFUs of C. albicans in the oral cavity compared to the WT mice infected with C. albicans (WTI). LFKO(-/-) I mice given hLF had a 3 log (P = 0·001) reduction in CFUs in the oral cavity compared to untreated LFKO(-/-) I mice. The severity of infection, observed by light microscopy, revealed that the tongue of the LFKO(-/-) I mice showed more white patches compared to WTI and LFKO(-/-) I + hLF mice. Scanning electron microscopic observations revealed that more filiform papillae were destroyed in LFKO(-/-) I mice when compared to WTI or LFKO(-/-) I + hLF mice. Human LF is important in protecting mice from oral C. albicans infection. Administered hLF may be used to prevent C. albicans infection. Human LF, a multifunctional iron-binding glycoprotein can be used as a therapeutic active ingredient in oral healthcare products against C. albicans. © 2014 The Society for Applied Microbiology.

Effect of Continuous Positive Airway Pressure on Stroke Rehabilitation: A Pilot Randomized Sham-Controlled Trial

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Khot, Sandeep P.; Davis, Arielle P.; Crane, Deborah A.; Tanzi, Patricia M.; Li Lue, Denise; Claflin, Edward S.; Becker, Kyra J.; Longstreth, W.T.; Watson, Nathaniel F.; Billings, Martha E.

2016-01-01

Study Objectives: Obstructive sleep apnea (OSA) predicts poor functional outcome after stroke and increases the risk for recurrent stroke. Less is known about continuous positive airway pressure (CPAP) treatment on stroke recovery. Methods: In a pilot randomized, double-blind, sham-controlled trial, adult stroke rehabilitation patients were assigned to auto-titrating or sham CPAP without diagnostic testing for OSA. Change in Functional Independence Measure (FIM), a measure of disability, was assessed between rehabilitation admission and discharge. Results: Over 18 months, 40 patients were enrolled and 10 withdrew from the study: 7 from active and 3 from sham CPAP (p > 0.10). For the remaining 30 patients, median duration of CPAP use was 14 days. Average CPAP use was 3.7 h/night, with at least 4 h nightly use among 15 patients. Adherence was not influenced by treatment assignment or stroke severity. In intention-to-treat analyses (n = 40), the median change in FIM favored active CPAP over sham but did not reach statistical significance (34 versus 26, p = 0.25), except for the cognitive component (6 versus 2.5, p = 0.04). The on-treatment analyses (n = 30) yielded similar results (total FIM: 32 versus 26, p = 0.11; cognitive FIM: 6 versus 2, p = 0.06). Conclusions: A sham-controlled CPAP trial among stroke rehabilitation patients was feasible in terms of recruitment, treatment without diagnostic testing and adequate blinding—though was limited by study retention and CPAP adherence. Despite these limitations, a trend towards a benefit of CPAP on recovery was evident. Tolerance and adherence must be improved before the full benefits of CPAP on recovery can be assessed in larger trials. Citation: Khot SP, Davis AP, Crane DA, Tanzi PM, Li Lue D, Claflin ES, Becker KJ, Longstreth WT, Watson NF, Billings ME. Effect of continuous positive airway pressure on stroke rehabilitation: a pilot randomized sham-controlled trial. J Clin Sleep Med 2016;12(7):1019–1026. PMID

Combination of Radiation and Burn Injury Alters FDG Uptake in Mice

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Carter, Edward A.; Winter, David; Tolman, Crystal; Paul, Kasie; Hamrahi, Victoria; Tompkins, Ronald; Fischman, Alan J.

2012-01-01

Radiation exposure and burn injury have both been shown to alter glucose utilization in vivo. The present study was designed to study the effect of burn injury combined with radiation exposure, on glucose metabolism in mice using [18F] Fluorodeoxyglucose (18FDG). Groups of male mice weighing approximately 30g were studied. Group 1 was irradiated with a 137Cs source (9 Gy). Group 2 received full thickness burn injury on 25% total body surface area followed by resuscitated with saline (2mL, IP). Group 3 received radiation followed 10 minutes later by burn injury. Group 4 were sham treated controls. After treatment, the mice were fasted for 23 hours and then injected (IV) with 50 µCi of 18FDG. One hour post injection, the mice were sacrificed and biodistribution was measured. Positive blood cultures were observed in all groups of animals compared to the shams. Increased mortality was observed after 6 days in the burn plus radiated group as compared to the other groups. Radiation and burn treatments separately or in combination produced major changes in 18FDG uptake by many tissues. In the heart, brown adipose tissue (BAT) and spleen, radiation plus burn produced a much greater increase (p<0.0001) in 18FDG accumulation than either treatment separately. All three treatments produced moderate decreases in 18FDG accumulation (p<0.01) in the brain and gonads. Burn injury, but not irradiation, increased 18FDG accumulation in skeletal muscle; however the combination of burn plus radiation decreased 18FDG accumulation in skeletal muscle. This model may be useful for understanding the effects of burns + irradiation injury on glucose metabolism and in developing treatments for victims of injuries produced by the combination of burn plus irradiation. PMID:23143615

Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial.

Science.gov (United States)

Mathiassen, Ole N; Vase, Henrik; Bech, Jesper N; Christensen, Kent L; Buus, Niels H; Schroeder, Anne P; Lederballe, Ole; Rickers, Hans; Kampmann, Ulla; Poulsen, Per L; Hansen, Klavs W; Btker, Hans E; Peters, Christian D; Engholm, Morten; Bertelsen, Jannik B; Lassen, Jens F; Langfeldt, Sten; Andersen, Gratien; Pedersen, Erling B; Kaltoft, Anne

2016-08-01

Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP. We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA). We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ± 12 mmHg (RDN) and 159 ± 14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ± 18.8 mmHg (RDN) vs. -6.0 ± 13.5 mmHg (SHAM)] and at 6 months [-6.1 ± 18.9 mmHg (RDN) vs. -4.3 ± 15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ± 2.7 (RDN) vs. 7.0 ± 2.5 (SHAM)].RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial. Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

Cellular and humoral immuno-stimulatory effects of diagnostic doses of X-rays in BALB/c mice

International Nuclear Information System (INIS)

Mortazavi, S.M.J.; Jafar-Zadeh, A.; Khosravi, M.H.; Mehdipour, L.A.; Behnejad, B.B.

2006-01-01

Objective: The immunosuppressive effects of high doses of ionizing radiation have long been known, while researchers know less about the effects of low dose radiation on the immune system. Recently, in human and experimental animal models it has been reported that low dose radiation may have immuno-stimulatory effects. The aim of this study was to evaluate the effects of low doses of diagnostic doses of X-rays on cell mediated and humoral immune responses in a Balb/c animal model. Materials and Methods: Using a conventional Villa radiography machine, three groups of male Balb/c mice were exposed one, two and three times to 30 mGy of X-rays. The measured surface dose was equal to the dose of a single view lateral lumbar radiography. Two to four hours after irradiation, the delayed type hypersensitivity (DTH) and humoral responses to sheep red blood cell (SRBC) were measured and compared to the responses of sham and control groups. Results: The mean titer of anti-SRBC antibodies in two-times irradiated (74.66± 26.12 ) and three-times irradiated (128 ± 70.1) groups were significantly higher than those of non-irradiated (26.66 ± 8.26) or sham irradiated (28.8 ± 20.86) group (p<0.001). However, no significant differences were observed between the mean titer of anti-SRBC antibodies in one-time irradiated (22.4 ± 8.76) and either non-irradiated or sham irradiated groups. Similarly, comparing DTH responses showed that the differences between either two-times irradiated (12.2 ± 3.9 ) or three times-irradiated (6.9 ± 3.7) and non-irradiated (4 ± 0.2) or sham irradiated (4.3 ± 3) groups was statistically significant (p<0.001). Conclusion: Theses results show that two-times and three-times irradiated mice demonstrate significant stimulatory effects on both DTH and antibody responses. However, one-time irradiated animals did not exhibit any bio- positive effect on DTH and humoral responses. Moreover, no statistically significant difference was observed between the DTH

Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice.

Science.gov (United States)

van der Geest, Rick; Ouweneel, Amber B; van der Sluis, Ronald J; Groen, Albert K; Van Eck, Miranda; Hoekstra, Menno

2016-09-01

Cholestatic liver disease is characterized by a disruption of bile flow, bile acid toxicity, liver injury, and hypercholesterolemia. Relatively high secretion of glucocorticoids by the adrenals has been observed under cholestatic conditions. Here we investigated a contribution of the rise in endogenous glucocorticoids to initial stage cholestasis pathology. Adrenalectomized or sham-operated control C57BL/6 mice were given an oral dose of alpha-naphthylisothiocyanate to induce cholestasis. Adrenalectomy effectively lowered plasma corticosterone levels (18±5ng/ml vs 472±58ng/ml; Phypercholesterolemia. In conclusion, we have shown that endogenous glucocorticoids exacerbate the liver injury and hypercholesterolemia associated with acute cholestasis in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

A spectral scheme for Kohn–Sham density functional theory of clusters

Energy Technology Data Exchange (ETDEWEB)

Banerjee, Amartya S., E-mail: baner041@umn.edu; Elliott, Ryan S., E-mail: relliott@umn.edu; James, Richard D., E-mail: james@umn.edu

2015-04-15

Starting from the observation that one of the most successful methods for solving the Kohn–Sham equations for periodic systems – the plane-wave method – is a spectral method based on eigenfunction expansion, we formulate a spectral method designed towards solving the Kohn–Sham equations for clusters. This allows for efficient calculation of the electronic structure of clusters (and molecules) with high accuracy and systematic convergence properties without the need for any artificial periodicity. The basis functions in this method form a complete orthonormal set and are expressible in terms of spherical harmonics and spherical Bessel functions. Computation of the occupied eigenstates of the discretized Kohn–Sham Hamiltonian is carried out using a combination of preconditioned block eigensolvers and Chebyshev polynomial filter accelerated subspace iterations. Several algorithmic and computational aspects of the method, including computation of the electrostatics terms and parallelization are discussed. We have implemented these methods and algorithms into an efficient and reliable package called ClusterES (Cluster Electronic Structure). A variety of benchmark calculations employing local and non-local pseudopotentials are carried out using our package and the results are compared to the literature. Convergence properties of the basis set are discussed through numerical examples. Computations involving large systems that contain thousands of electrons are demonstrated to highlight the efficacy of our methodology. The use of our method to study clusters with arbitrary point group symmetries is briefly discussed.

A spectral scheme for Kohn–Sham density functional theory of clusters

International Nuclear Information System (INIS)

Banerjee, Amartya S.; Elliott, Ryan S.; James, Richard D.

2015-01-01

Starting from the observation that one of the most successful methods for solving the Kohn–Sham equations for periodic systems – the plane-wave method – is a spectral method based on eigenfunction expansion, we formulate a spectral method designed towards solving the Kohn–Sham equations for clusters. This allows for efficient calculation of the electronic structure of clusters (and molecules) with high accuracy and systematic convergence properties without the need for any artificial periodicity. The basis functions in this method form a complete orthonormal set and are expressible in terms of spherical harmonics and spherical Bessel functions. Computation of the occupied eigenstates of the discretized Kohn–Sham Hamiltonian is carried out using a combination of preconditioned block eigensolvers and Chebyshev polynomial filter accelerated subspace iterations. Several algorithmic and computational aspects of the method, including computation of the electrostatics terms and parallelization are discussed. We have implemented these methods and algorithms into an efficient and reliable package called ClusterES (Cluster Electronic Structure). A variety of benchmark calculations employing local and non-local pseudopotentials are carried out using our package and the results are compared to the literature. Convergence properties of the basis set are discussed through numerical examples. Computations involving large systems that contain thousands of electrons are demonstrated to highlight the efficacy of our methodology. The use of our method to study clusters with arbitrary point group symmetries is briefly discussed

Validation Study of Kim's Sham Needle by Measuring Facial Temperature: An N-of-1 Randomized Double-Blind Placebo-Controlled Clinical Trial

Directory of Open Access Journals (Sweden)

Sanghun Lee

2012-01-01

Full Text Available Introduction. In 2008, Kim's sham needle was developed to improve the quality of double-blinded studies. The aim of this study is to validate Kim's sham needle by measuring facial temperature. Methods. We designed “N-of-1” trials involving 7 smokers. One session was composed of 2 stimulations separated by a 2 h washout period. Six sessions were applied daily for all subjects. Infrared thermal imaging was used to examine the effects of acupuncture (HT8, KI2 on facial temperature following smoking-induced decrease. Results. All subjects demonstrated decreased temperatures after sham needle treatment, but 5 of the 7 subjects showed increased temperatures after real needle treatment. 6 of the 7 subjects showed a significant difference (P<0.05 between treatments with real and sham needles. Thus, the physiological stimulation of Kim's sham needle is different from that of a real needle, suggesting that Kim's sham needle is a potential inactive control intervention.

MDMA reinstates cocaine-seeking behaviour in mice.

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Trigo, José Manuel; Orejarena, Maria Juliana; Maldonado, Rafael; Robledo, Patricia

2009-06-01

MDMA effects are mediated by monoaminergic systems, which seem to play a central role in cocaine craving and relapse. CD1 mice trained to self-administer cocaine (1 mg/kg/infusion) underwent an extinction procedure in which the cues contingent with drug self-administration remained present. Mice achieving extinction were injected with MDMA (10 mg/kg), d-amphetamine (1 and 2 mg/kg) or saline and tested for reinstatement. Acute MDMA, but not d-amphetamine or saline reinstated cocaine-seeking behaviour in mice in which cocaine self-administration and contingent cues were previously extinguished. Acute MDMA can reinstate cocaine-seeking behaviour in mice.

[Role of immune-related GTPase M1 in cortical neurons autophagy of mice with sepsis-induced brain injury].

Science.gov (United States)

Huang, Qun; Chen, Bin; Li, Yafei; Li, Xihong

2017-12-28

To investigate the role of immune-related GTPase M1 (IRGM1) in cortical neurons autophagy in mice with sepsis induced brain injury (SIBI).
 Methods: Sixty wild-type C57BL/6 mice and sixty IRGM1 gene knockout C57BL/6 mice were randomly divided into 4 groups: a sham-operated wild-type (SWT) group, a cecal ligation and puncture (CLP) model wild-type (MWT) group, a sham-operated knockout (SKO) group, and a CLP model knockout (MKO) group. Models of mice with sepsis were established by CLP. Six hours of after CLP, the neurobehavioral scores for mice were recorded. The mice were diagnosed with SIBI and enrolled for the studies in next step if the neurobehavioral score was less than 6 in the MWT and MKO groups. The sham operation group only opened the abdominal cavity without CLP. Pathological changes in mouse cerebral cortex were observed by HE staining. Electron microscope was used to observe the ultrastructure of autophagy in cortical neurons. The expression of IRGM1 and INF-γ mRNA in the cerebral cortex of mice were detected by Real time quantitative PCR. The protein expression of microtubule-associated protein 1 light chain 3 (LC3)-II, LC3-I, sequestosome-1 (SQSTM1) and IRGM1 were measured by Western blot. Immunofluorescence staining was used to examine the expression of IRGM1 in mouse cortical neurons.
 Results: In the MWT group, the cortical neurons showed dilated endoplasmic reticulum, swelling mitochondria, and increased number of autophagosomes after 6 or 24 h of CLP in contrast to the SWT group. At 6 h after CLP, the expression of LC3-II in the cerebral cortex began to up-regulate, and the up-regulation was maintained till 96 h after CLP; on the contrary, SQSTM1 began to decline after 6 h of CLP. Compared with SWT group, IRGM1 was strongly up-regulated in the cerebral cortex of mice at both mRNA and protein levels in the MWT group after 12 h of CLP, and the mRNA expression of IFN-γ was also increased significantly (PSIBI was 90% (27/30) in the MWT group

Kohn-Sham Theory for Ground-State Ensembles

International Nuclear Information System (INIS)

Ullrich, C. A.; Kohn, W.

2001-01-01

An electron density distribution n(r) which can be represented by that of a single-determinant ground state of noninteracting electrons in an external potential v(r) is called pure-state v -representable (P-VR). Most physical electronic systems are P-VR. Systems which require a weighted sum of several such determinants to represent their density are called ensemble v -representable (E-VR). This paper develops formal Kohn-Sham equations for E-VR physical systems, using the appropriate coupling constant integration. It also derives local density- and generalized gradient approximations, and conditions and corrections specific to ensembles

Concentration of metallothionein in mice livers after a small dose of irradiation

Energy Technology Data Exchange (ETDEWEB)

Saitou, Mikio; Yanai, Takanori; Hasegawa, Hidenao; Otsu, Hiroshi; Sato, Fumiaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan); Akata, Naofumi; Kanaiwa-Kudo, Shouko; Matsumoto, Tsuneya; Noda, Yuko

1998-12-01

This study was made to determine whether metallothionein (MT) is induced by a small dose (0.5 Gy) irradiation. One hundred B6C3F1/Nrs mice of each sex, 8-10 weeks old, were used in the sham study (unirradiated controls) and experimental (irradiated) groups. Eighty mice of each sex were given acute whole body irradiation with {sup 197}Cs{gamma}-rays under SPF conditions; two doses of 0.5 and 5.0 Gy at 30 cm distance from the source at the rate of 0.563 Gy/min. Twenty mice of each sex were used in the sham study. Every ten male and female mouse was killed by cervical dislocation on days 1, 7, 14 and 21 after irradiation. The same numbers of male and female control mice were killed on days 0 and 21. Livers were removed immediately after death, and concentration of MT was examined. In both the males and females, the MT concentration of the 5 Gy-group peaked on the first day after irradiation, and there was no difference in comparison with the control values between the 7th and 21st days. In contrast, on no day did the MT concentration for the 0.5 Gy-group showed a significant difference from the control group. The time dependency patterns of the female and male mice also showed no significant differences for 5 Gy- and 0.5 Gy-groups, but the mean values of the MT concentration was lower in the males than in the females on the 1st day. Results of the direct quantitation of MT by the enzyme-linked immunoabsorbent assay (ELISA) also showed peak MT accumulation on the 1st day for both male and female mice. These were also shown by the atomic absorption spectrometry (AAS) and the inductively coupled plasma mass spectrometry (ICP-MS) analyses. But peak heights for the males and females showed a tendency inverse to that of the AAS and ICP-MS analyses. This discrepancy is attributable to the technical problem encountered in the experiment. On the basis of our findings, MT does not seem to be related to acquired radioresistance in mice. (K.H.)

Propagators for the time-dependent Kohn-Sham equations

International Nuclear Information System (INIS)

Castro, Alberto; Marques, Miguel A. L.; Rubio, Angel

2004-01-01

In this paper we address the problem of the numerical integration of the time-dependent Schroedinger equation i∂ t φ=Hφ. In particular, we are concerned with the important case where H is the self-consistent Kohn-Sham Hamiltonian that stems from time-dependent functional theory. As the Kohn-Sham potential depends parametrically on the time-dependent density, H is in general time dependent, even in the absence of an external time-dependent field. The present analysis also holds for the description of the excited state dynamics of a many-electron system under the influence of arbitrary external time-dependent electromagnetic fields. Our discussion is separated in two parts: (i) First, we look at several algorithms to approximate exp(A), where A is a time-independent operator [e.g., A=-iΔtH(τ) for some given time τ]. In particular, polynomial expansions, projection in Krylov subspaces, and split-operator methods are investigated. (ii) We then discuss different approximations for the time-evolution operator, such as the midpoint and implicit rules, and Magnus expansions. Split-operator techniques can also be modified to approximate the full time-dependent propagator. As the Hamiltonian is time dependent, problem (ii) is not equivalent to (i). All these techniques have been implemented and tested in our computer code OCTOPUS, but can be of general use in other frameworks and implementations

Influence of electromagnetic pulse on the offspring sex ratio of male BALB/c mice.

Science.gov (United States)

Li, Jin-Hui; Jiang, Da-Peng; Wang, Ya-Feng; Yan, Jia-Jia; Guo, Qi-Yan; Miao, Xia; Lang, Hai-Yang; Xu, Sheng-Long; Liu, Jun-Ye; Guo, Guo-Zhen

2017-09-01

Public concern is growing about the exposure to electromagnetic fields (EMF) and its effect on male reproductive health. Detrimental effect of EMF exposure on sex hormones, reproductive performance and sex-ratio was reported. The present study was designed to clarify whether paternal exposure to electromagnetic pulse (EMP) affects offspring sex ratio in mice. 50 male BALB/c mice aged 5-6 weeks were exposed to EMP daily for 2 weeks before mated with non-exposed females at 0d, 7d, 14d, 21d and 28d after exposure. Sex hormones including total testosterone, LH, FSH, and GnRH were detected using radioimmunoassay. The sex ratio was examined by PCR and agarose gel electrophoresis. The results of D0, D21 and D28 showed significant increases compared with sham-exposed groups. The serum testosterone increased significantly in D0, D14, D21, and D28 compared with sham-exposed groups (p<0.05). Overall, this study suggested that EMP exposure may lead to the disturbance of reproductive hormone levels and affect the offspring sex ratio. Copyright © 2017. Published by Elsevier B.V.

Dysregulated cytokine expression by CD4+ T cells from post-septic mice modulates both Th1 and Th2-mediated granulomatous lung inflammation.

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William F Carson

Full Text Available Previous epidemiological studies in humans and experimental studies in animals indicate that survivors of severe sepsis exhibit deficiencies in the activation and effector function of immune cells. In particular, CD4+ T lymphocytes can exhibit reduced proliferative capacity and improper cytokine responses following sepsis. To further investigate the cell-intrinsic defects of CD4+ T cells following sepsis, splenic CD4+ T cells from sham surgery and post-septic mice were transferred into lymphopenic mice. These recipient mice were then subjected to both TH1-(purified protein derivative and TH2-(Schistosoma mansoni egg antigen driven models of granulomatous lung inflammation. Post-septic CD4+ T cells mediated smaller TH1 and larger TH2 lung granulomas as compared to mice receiving CD4+ T cells from sham surgery donors. However, cytokine production by lymph node cells in antigen restimulation assays indicated increased pan-specific cytokine expression by post-septic CD4+ T cell recipient mice in both TH1 and TH2 granuloma models. These include increased production of T(H2 cytokines in TH1 inflammation, and increased production of T(H1 cytokines in TH2 inflammation. These results suggest that cell-intrinsic defects in CD4+ T cell effector function can have deleterious effects on inflammatory processes post-sepsis, due to a defect in the proper regulation of TH-specific cytokine expression.

Accurate Valence Ionization Energies from Kohn-Sham Eigenvalues with the Help of Potential Adjustors.

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Thierbach, Adrian; Neiss, Christian; Gallandi, Lukas; Marom, Noa; Körzdörfer, Thomas; Görling, Andreas

2017-10-10

An accurate yet computationally very efficient and formally well justified approach to calculate molecular ionization potentials is presented and tested. The first as well as higher ionization potentials are obtained as the negatives of the Kohn-Sham eigenvalues of the neutral molecule after adjusting the eigenvalues by a recently [ Görling Phys. Rev. B 2015 , 91 , 245120 ] introduced potential adjustor for exchange-correlation potentials. Technically the method is very simple. Besides a Kohn-Sham calculation of the neutral molecule, only a second Kohn-Sham calculation of the cation is required. The eigenvalue spectrum of the neutral molecule is shifted such that the negative of the eigenvalue of the highest occupied molecular orbital equals the energy difference of the total electronic energies of the cation minus the neutral molecule. For the first ionization potential this simply amounts to a ΔSCF calculation. Then, the higher ionization potentials are obtained as the negatives of the correspondingly shifted Kohn-Sham eigenvalues. Importantly, this shift of the Kohn-Sham eigenvalue spectrum is not just ad hoc. In fact, it is formally necessary for the physically correct energetic adjustment of the eigenvalue spectrum as it results from ensemble density-functional theory. An analogous approach for electron affinities is equally well obtained and justified. To illustrate the practical benefits of the approach, we calculate the valence ionization energies of test sets of small- and medium-sized molecules and photoelectron spectra of medium-sized electron acceptor molecules using a typical semilocal (PBE) and two typical global hybrid functionals (B3LYP and PBE0). The potential adjusted B3LYP and PBE0 eigenvalues yield valence ionization potentials that are in very good agreement with experimental values, reaching an accuracy that is as good as the best G 0 W 0 methods, however, at much lower computational costs. The potential adjusted PBE eigenvalues result in

Comparing Phlebotomy by Tail Tip Amputation, Facial Vein Puncture, and Tail Vein Incision in C57BL/6 Mice by Using Physiologic and Behavioral Metrics of Pain and Distress.

Science.gov (United States)

Moore, Elizabeth S; Cleland, Thomas A; Williams, Wendy O; Peterson, Christine M; Singh, Bhupinder; Southard, Teresa L; Pasch, Bret; Labitt, Rachael N; Daugherity, Erin K

2017-05-01

Tail tip amputation with minimal restraint is not widely used for mouse phlebotomy. In part, this infrequency may reflect policies influenced by tail tip amputation procedures for genotyping, which involve greater handling and tissue removal. To assess tail tip amputation with minimal restraint as a phlebotomy technique, we compared it with 2 more common methods: scruffing with facial vein puncture and lateral tail vein incision with minimal restraint. Blood glucose levels, audible and ultrasonic vocalizations, postphlebotomy activity and grooming behavior, open field and elevated plus maze behaviors, nest-building scores, and histologic changes at the phlebotomy site were evaluated. Mice in the facial vein phlebotomy group produced more audible vocalizations, exhibited lower postphlebotomy activity in the open field, and had more severe histologic changes than did mice in the tail incision and tail tip amputation groups. Facial vein phlebotomy did not affect grooming behavior relative to sham groups, whereas tail vein incision-but not tail tip amputation-increased tail grooming compared with that in control mice. Blood glucose levels, nest-building scores, and elevated plus maze behavior did not differ between groups, and no mice in any group produced ultrasonic vocalizations. Tail tip amputation mice did not perform differently than sham mice in any metric analyzed, indicating that this technique is a potentially superior method of blood collection in mice in terms of animal wellbeing.

1-Hz rTMS in the treatment of tinnitus: A sham-controlled, randomized multicenter trial.

Science.gov (United States)

Landgrebe, Michael; Hajak, Göran; Wolf, Stefan; Padberg, Frank; Klupp, Philipp; Fallgatter, Andreas J; Polak, Thomas; Höppner, Jacqueline; Haker, Rene; Cordes, Joachim; Klenzner, Thomas; Schönfeldt-Lecuona, Carlos; Kammer, Thomas; Graf, Erika; Koller, Michael; Kleinjung, Tobias; Lehner, Astrid; Schecklmann, Martin; Pöppl, Timm B; Kreuzer, Peter; Frank, Elmar; Langguth, Berthold

Chronic tinnitus is a frequent, difficult to treat disease with high morbidity. This multicenter randomized, sham-controlled trial investigated the efficacy and safety of 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal cortex in patients with chronic tinnitus. Tinnitus patients were randomized to receive 10 sessions of either real or sham 1-Hz-rTMS (2000 stimuli, 110% motor threshold) to the left temporal cortex. The primary outcome was the change in the sum score of the tinnitus questionnaire (TQ) of Goebel and Hiller from baseline to end of treatment. A total of 163 patients were enrolled in the study (real rTMS: 75; sham rTMS: 78). At day 12, the baseline mean of 43.1 TQ points in 71 patients assigned to real rTMS changed by -0.5 points; it changed by 0.5 points from a baseline of 42.1 in 75 patients randomized to sham rTMS (adjusted mean difference between groups: -1.0; 95.19% confidence interval: -3.2 to 1.2; p = 0.36). All secondary outcome measures including measures of depression and quality of life showed no significant differences either (p > 0.11). The number of participants with side-effects or adverse events did not differ between groups. Real 1-Hz-rTMS over the left temporal cortex was well tolerated but not superior compared with sham rTMS in improving tinnitus severity. These findings are in contrast to results from studies with smaller sample sizes and put the efficacy of this rTMS protocol for treatment of chronic tinnitus into question. Controlled Trials: http://www.isrctn.com/ISRCTN89848288. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired bone healing at tooth extraction sites in CD24-deficient mice: A pilot study.

Science.gov (United States)

Avivi-Arber, Limor; Avivi, Doran; Perez, Marilena; Arber, Nadir; Shapira, Shiran

2018-01-01

To use a micro-computed tomography (micro-CT) to quantify bone healing at maxillary first molar extraction sites, and test the hypothesis that bone healing is impaired in CD24-knockout mice as compared with wild-type C57BL/6J mice. Under ketamine-xylazine general anaesthesia, mice had either extraction of the right maxillary first molar tooth or sham operation. Mice were sacrificed 1 (n = 12/group), 2 (n = 6/group) or 4 (n = 6/group) weeks postoperatively. The right maxillae was disected. Micro-CT was used to quantify differences in bone microstructural features at extrction sites, between CD24-knockout mice and wild-type mice. CD24-Knockout mice displayed impaired bone healing at extraction sites that was manifested as decreased trabecular bone density, and decreased number and thickness of trabeculae. This pilot study suggests that CD24 plays an important role in extraction socket bone healing and may be used as a novel biomarker of bone quality and potential therapeutic target to improve bone healing and density following alveolar bone injury.

A urodynamic study of surface neuromodulation versus sham in detrusor instability and sensory urgency.

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Bower, W F; Moore, K H; Adams, R D; Shepherd, R

1998-12-01

We studied the effect of surface neuromodulation on cystometric pressure and volume parameters in women with detrusor instability or sensory urgency. Electrical current was delivered to the suprapubic region and third sacral foramina via a transcutaneous electrical nerve stimulator with sham neuromodulation control. A consecutive series of women with proved detrusor instability or sensory urgency were randomized to 3 surface neuromodulation groups. Volume and pressure parameters were the main outcomes of transcutaneous electrical nerve stimulation applied during second cystometric fill. Sham transcutaneous electrical nerve stimulation did not alter the outcome measures. However, neuromodulation delivered across the suprapubic and sacral skin effected a reduction in mean maximum height of detrusor contraction. A current which inhibits motor activity was not superior to that which inhibits sensory perception in reducing detrusor pressure. Response in sensory urgency was poor. Results from our sham controlled study suggest that short-term surface neuromodulation via transcutaneous electrical nerve stimulation may have a role in the treatment of detrusor instability. Future studies must examine the clinical effect of long-term surface neuromodulation.

Gentlest ascent dynamics for calculating first excited state and exploring energy landscape of Kohn-Sham density functionals.

Science.gov (United States)

Li, Chen; Lu, Jianfeng; Yang, Weitao

2015-12-14

We develop the gentlest ascent dynamics for Kohn-Sham density functional theory to search for the index-1 saddle points on the energy landscape of the Kohn-Sham density functionals. These stationary solutions correspond to excited states in the ground state functionals. As shown by various examples, the first excited states of many chemical systems are given by these index-1 saddle points. Our novel approach provides an alternative, more robust way to obtain these excited states, compared with the widely used ΔSCF approach. The method can be easily generalized to target higher index saddle points. Our results also reveal the physical interest and relevance of studying the Kohn-Sham energy landscape.

The Healing of Bone Marrow-Derived Stem Cells on Motor Functions in Acute Spinal Cord Injury of Mice

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N Gashmardi

2016-10-01

Full Text Available Background & aim: Spinal cord injury is a devastating damage that can cause motor and sensory deficits reducing quality of life and life expectancy of patients. Stem cell transplantation can be one of the promising therapeutic strategies. Bone marrow is a rich source of stem cells that is able to differentiate into various cell types. In this study, bone marrow stem cells were transplanted into mice spinal cord injury model to evaluate the motor function test. Methods: Bone marrow stem cells were isolated from 3 mice. Thirty six mice were randomly divided into 3 groups: the control, sham and experimental. In sham group, mice were subjected to spinal cord compression. In experimental group, one day after lesion, isolated stem cells (200,000 were injected intravenously. Assessment of locomotor function was done by Toyama Mouse Score (TMS after 1, 2, 3, 4, 5 week post-injury. The data were analyzed using one-way Analysis of Variance and Tukey tests and statistical software Graph Pad and SPSS.P > 0/05 was considered as significant difference.  Results: The score of TMS after cell transplantation was higher in cell transplantation group (experimental, while it was significantly higher after fifth week when compared to other groups. Conclusion: The increase in TMS score in cell transplantation group showed that injection of stem cells in acute spinal cord injury can have a therapeutic effect and promote locomotor function.

The combined effects of soya isoflavones and resistant starch on equol production and trabecular bone loss in ovariectomised mice.

Science.gov (United States)

Tousen, Yuko; Matsumoto, Yu; Matsumoto, Chiho; Nishide, Yoriko; Nagahata, Yuya; Kobayashi, Isao; Ishimi, Yoshiko

2016-07-01

Equol is a metabolite of the soya isoflavone (ISO) daidzein that is produced by intestinal microbiota. Equol has greater oestrogenic activity compared with other ISO, and it prevents bone loss in postmenopausal women. Resistant starch (RS), which has a prebiotic activity and is a dietary fibre, was reported to promote equol production. Conversely, the intestinal microbiota is reported to directly regulate bone health by reducing inflammatory cytokine levels and T-lymphocytes in bone. The present study evaluated the combined effects of diet supplemented with ISO and RS on intestinal microbiota, equol production, bone mineral density (BMD) and inflammatory gene expression in the bone marrow of ovariectomised (OVX) mice. Female ddY strain mice, aged 8 weeks, were either sham-operated (Sham, n 7) or OVX. OVX mice were randomly divided into the following four groups (seven per group): OVX control (OVX); OVX fed 0·05 % ISO diet (OVX+ISO); OVX fed 9 % RS diet (OVX+RS); and OVX fed 0·05 % ISO- and 9 % RS diet (OVX+ISO+RS). After 6 weeks, treatment with the combination of ISO and RS increased equol production, prevented the OVX-induced decline in trabecular BMD in the distal femur by modulating the enteric environment and altered OVX-induced inflammation-related gene expression in the bone marrow. However, there were no significant differences in bone parameters between the ISO+RS and ISO-alone groups in OVX mice. Our findings suggest that the combination of ISO and RS might alter intestinal microbiota and immune status in the bone marrow, resulting in attenuated bone resorption in OVX mice.

Assessing Anticonvulsant Effect of Aqueous Extract of Datura Stramonium Seed on PTZ-Induced Seizures in the Male Mice

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S Namvar Aghdash

2015-11-01

Full Text Available Background: Epilepsy is one of the most common neurological disorders that affect social, economic and biological aspects of the human life. Many epileptic patients have uncontrolled seizures and medication-related side effects despite adequate pharmacological treatment. The use of plant extracts is proposed as a therapeutic modality in order to treat different diseases. Datura plant has long been used in the traditional medicine in regard with some nervous disorders like epilepsy. Thus, this study aimed to provide a scientific basis investigating the effect of Datura aqueous extract on PTZ-induced seizures in the male mice. Methods: In this experimental study, 40 male mice were randomly allocated into 5 equal groups including: one control group, one sham group and three experimental groups. The experimental groups received 50, 100 and 150 mg/kg of aqueous extract of Datura Stramonium seed via gavage for 30 days, and the sham group received stilled water via gavage. Pentylenetetrazol (PTZ 35 mg/kg, i.p were injected into control, sham and experimental groups 30 minutes after gavage in order to induce the seizure. Then latency time of seizure onset, seizure duration and seizure phases were measured and recorded in the experimental, sham and control groups. The data analysis was carried out via one way ANOVA and Tukey post-hoc tests.  Moreover, difference less than 0.05 (P<0.05 was considered significant. Results: The study findings revealed that the aqueous extract of Datura Stramonium seed produced a significant effect on PTZ-induced seizure. In addition, Datura increases latency time of seizure onset (P˂0.01, inhibits progress of seizure stages (P˂0.05 and decreases seizure duration (P˂0.001. Conclusion: The results obtained from the present study indicated that extract of this plant has anticonvulsant effects on PTZ-induced seizure. As a result, it seems to be beneficial to the epilepsy treatment.

Pharmacokinetic Analysis of 64Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice

DEFF Research Database (Denmark)

Li, Fan; Jørgensen, Jesper Tranekjær; Madsen, Jacob

2015-01-01

The aim of this study was to evaluate the feasibility to perform voxel-wise kinetic modeling on datasets obtained from tumor-bearing mice that underwent dynamic PET scans with 64Cu-ATSM and extract useful physiological parameters.METHODS: Tumor-bearing mice underwent 90-min dynamic PET scans...... relevant parameters from voxel-wise pharmacokinetic analysis to be used for preclinical validation of 64Cu-ATSM as a hypoxia-specific PET tracer....

Bioassay in BALB/c mice exposed to low dose rate radiation

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Km, Sung Dae; Gong, Eun Ji; Bae, Min Ji; Yang, Kwang Mo; Kim, Joong Sun [Dongnam Institute of Radiological and Medical Sciences, Suwon (Korea, Republic of)

2012-09-15

The present study was performed to investigate the toxicity of low-dose-rate irradiation in BALB/c mice. Twenty mice of each sex were randomly assigned to four groups of five mice each and were exposed to 0 (sham), 0.02, 0.2, or 2 Gy, equivalents to low-dose-rate irradiation to 3.49 mGy{center_dot}h{sup -1}. Urine, blood, and blood biochemistry were analyzed, and organ weight was measured. The low-dose-rate irradiation did not induce any toxicologically significant changes in mortality, clinical signs, body weight, food and water consumption, urinalysis, and serum biochemistry. However, the weights of reproductive organs including the testis, ovary, and uterus decreased in a dose-dependent manner. Irradiation at 2 Gy significantly decreased the testis, ovary, and uterus weights, but did not change the weights of other organs. There were no adverse effects on hematology in any irradiated group and only the number of neutrophils increased dose dependently. The low-dose-rate irradiation exposure did not cause adverse effects in mice at dose levels of 2 Gy or less, but the reproductive systems of male and female mice showed toxic effects.

Intermittent fasting attenuates increases in neurogenesis after ischemia and reperfusion and improves recovery.

Science.gov (United States)

Manzanero, Silvia; Erion, Joanna R; Santro, Tomislav; Steyn, Frederik J; Chen, Chen; Arumugam, Thiruma V; Stranahan, Alexis M

2014-05-01

Intermittent fasting (IF) is neuroprotective across a range of insults, but the question of whether extending the interval between meals alters neurogenesis after ischemia remains unexplored. We therefore measured cell proliferation, cell death, and neurogenesis after transient middle cerebral artery occlusion (MCAO) or sham surgery (SHAM) in mice fed ad libitum (AL) or maintained on IF for 3 months. IF was associated with twofold reductions in circulating levels of the adipocyte cytokine leptin in intact mice, but also prevented further reductions in leptin after MCAO. IF/MCAO mice also exhibit infarct volumes that were less than half those of AL/MCAO mice. We observed a 30% increase in basal cell proliferation in the hippocampus and subventricular zone (SVZ) in IF/SHAM, relative to AL/SHAM mice. However, cell proliferation after MCAO was limited in IF mice, which showed twofold increases in cell proliferation relative to IF/SHAM, whereas AL/MCAO mice exhibit fivefold increases relative to AL/SHAM. Attenuation of stroke-induced neurogenesis was correlated with reductions in cell death, with AL/MCAO mice exhibiting twice the number of dying cells relative to IF/MCAO mice. These observations indicate that IF protects against neurological damage in ischemic stroke, with circulating leptin as one possible mediator.

Acute myeloid leukemia induction in CBA/H mice by irradiation with fission neutrons as a function of exposure rate

International Nuclear Information System (INIS)

Huiskamp, R.

1991-01-01

Radiation-induced acute myeloid leukemia (AML) in male CBA/H mice was used as a model for investigation of the effect of reduced fast fission neutron exposure rates on radiation-induced carcinogenesis. Groups of about 90 male CBA/H mice were irradiated or sham-irradiated at the age of 15-20 weeks. The animals were exposed to 400 mGy fast fission neutrons at exposure rates of 2, 10 or 100 mGy/min. The investigation clearly showed that reducing the exposure rate of high-LET fast fission neutrons had no influence on the incidence of AML or on the survival of the irradiated mice. In contrast, a higher incidence of lymphosarcomas was observed in mice irradiated with higher exposure rates. (orig./MG)

Acute myeloid leukemia induction in CBA/H mice by irradiation with fission neutrons as a function of exposure rate

Energy Technology Data Exchange (ETDEWEB)

Huiskamp, R [Stichting Energieonderzoek Centrum Nederland, Petten (Netherlands). Radiobiology and Radio-Ecology Unit

1991-06-01

Radiation-induced acute myeloid leukemia (AML) in male CBA/H mice was used as a model for investigation of the effect of reduced fast fission neutron exposure rates on radiation-induced carcinogenesis. Groups of about 90 male CBA/H mice were irradiated or sham-irradiated at the age of 15-20 weeks. The animals were exposed to 400 mGy fast fission neutrons at exposure rates of 2, 10 or 100 mGy/min. The investigation clearly showed that reducing the exposure rate of high-LET fast fission neutrons had no influence on the incidence of AML or on the survival of the irradiated mice. In contrast, a higher incidence of lymphosarcomas was observed in mice irradiated with higher exposure rates. (orig./MG).

Kohn-Sham orbitals and potentials from quantum Monte Carlo molecular densities

International Nuclear Information System (INIS)

Varsano, Daniele; Barborini, Matteo; Guidoni, Leonardo

2014-01-01

In this work we show the possibility to extract Kohn-Sham orbitals, orbital energies, and exchange correlation potentials from accurate Quantum Monte Carlo (QMC) densities for atoms (He, Be, Ne) and molecules (H 2 , Be 2 , H 2 O, and C 2 H 4 ). The Variational Monte Carlo (VMC) densities based on accurate Jastrow Antisymmetrised Geminal Power wave functions are calculated through different estimators. Using these reference densities, we extract the Kohn-Sham quantities with the method developed by Zhao, Morrison, and Parr (ZMP) [Phys. Rev. A 50, 2138 (1994)]. We compare these extracted quantities with those obtained form CISD densities and with other data reported in the literature, finding a good agreement between VMC and other high-level quantum chemistry methods. Our results demonstrate the applicability of the ZMP procedure to QMC molecular densities, that can be used for the testing and development of improved functionals and for the implementation of embedding schemes based on QMC and Density Functional Theory

Effects of continuous positive airway pressure on energy intake in obstructive sleep apnea: A pilot sham-controlled study

Science.gov (United States)

Shechter, Ari; Kovtun, Kyle; St-Onge, Marie-Pierre

2016-01-01

Obesity is among the leading risk factors for obstructive sleep apnea (OSA). A reciprocal relationship between obesity and OSA has been proposed, which may be due to excessive food intake. We conducted a pilot study to test the effects of continuous positive airway pressure (CPAP) on energy intake (EI) in OSA patients using a sham-controlled crossover design. In-laboratory total daily EI was assessed after 2 mo of active and sham CPAP. Four men were enrolled (age ± SEM: 51.8 ± 2.1 y; body mass index: 31.5 ± 1.5 kg/m2). All received active treatment first. Meals (breakfast, lunch, dinner, snack) were served in excess portions at fixed times and additional palatable snacks were freely available throughout the day. Total EI was lower after active (3744 ± 511 kcal/d) vs. sham (4030 ± 456 kcal/d) CPAP but this difference was not significant (p = 0.51) due to variability in the free snack intake. When only fixed eating occasions were considered, daily EI was significantly lower in the active (3105 ± 513 kcal/d) vs. sham (3559 ± 420 kcal/d) condition (p = 0.006). This small pilot and feasibility study is the first to utilize a sham-controlled design to investigate the effects of CPAP treatment on objective measures of EI. Findings suggest that CPAP may cause a reduction in fixed meal intake. In demonstrating feasibility of study methodology, our study also suggests a larger randomized sham-controlled trial be conducted to fully characterize the effects of CPAP treatment on EI and energy balance overall. PMID:27769851

Effect of Lepidium meyenii (maca) on testicular function of mice with chemically and physically induced subfertility.

Science.gov (United States)

Valdivia Cuya, M; Yarasca De La Vega, K; Lévano Sánchez, G; Vásquez Cavero, J; Temoche García, H; Torres Torres, L; Cruz Ornetta, V

2016-10-01

The aim of this study was to evaluate the effect of Lepidium meyenii (maca) in chemically and physically subfertile mice. After 35 days, the following groups of mice were evaluated: control, sham, chemical subfertility, chemical subfertility-maca-supplemented, physical subfertility, physical subfertility-maca-supplemented and maca-supplemented only. Motility (32.36% ± 5.34%) and sperm count (44.4 ± 5.37 × 10(6) /ml) in the chemically and physically subfertile mice (11.81% ± 4.06%, 17.34 ± 13.07 × 10(6) /ml) decreased compared to the control (75.53% ± 2.97% and 57.4 ± 19.6 10(6) /ml) and sham (53.5% ± 7.86% and 58.4 ± 14.10 10(6) /ml). Maca was able to reverse the deleterious effect of motility (76.36 ± 1.97) as well as sperm count (53.5 ± 9.18 × 10(6) /ml) on chemical subfertility. In contrast, maca did not reverse the effects of induced physical subfertility nor motility (18.78% ± 14.41%) or sperm count (20.17 ± 11.20 × 10(6) /ml). The percentage of sperm DNA fragmentation in the physically subfertile mice increased (11.1% ± 19.29%) compared to the control (0.84% ± 0.85%). However, in the physically subfertile group, maca decreased sperm DNA fragmentation (2.29% ± 2.30%) closer to the sham (1.04% ± 0.62%) and the control (0.84% ± 0.85%). The group supplemented only with maca showed 0.54% ± 0.50% of spermatozoa with DNA fragmentation. Yet, the differences observed were statistically not significant. In conclusion, it appears that maca activates the cytochrome P450 system after chemically induced subfertility. However, it does not reverse the low mitochondrial membrane potential in spermatozoa compromised in the physical subfertility group. © 2016 Blackwell Verlag GmbH.

The effects of extremely low frequency magnetic fields on mutation induction in mice

Energy Technology Data Exchange (ETDEWEB)

Wilson, James W. [Department of Genetics, University of Leicester, Leicester LE1 7RH (United Kingdom); Haines, Jackie; Sienkiewicz, Zenon [Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 0RQ (United Kingdom); Dubrova, Yuri E., E-mail: yed2@le.ac.uk [Department of Genetics, University of Leicester, Leicester LE1 7RH (United Kingdom)

2015-03-15

Highlights: • The effects of 50 Hz magnetic fields on mutation induction in mice were analyzed. • The frequency of ESTR mutation was established in sperm and blood. • Exposure to 10–300 μT for 2 and 15 h did not result in mutation induction. • Mutagenic effects of 50 Hz magnetic fields are likely to be negligible. - Abstract: The growing human exposure to extremely low frequency (ELF) magnetic fields has raised a considerable concern regarding their genotoxic effects. The aim of this study was to evaluate the in vivo effects of ELF magnetic fields irradiation on mutation induction in the germline and somatic tissues of male mice. Seven week old BALB/c × CBA/Ca F{sub 1} hybrid males were exposed to 10, 100 or 300 μT of 50 Hz magnetic fields for 2 or 15 h. Using single-molecule PCR, the frequency of mutation at the mouse Expanded Simple Tandem Repeat (ESTR) locus Ms6-hm was established in sperm and blood samples of exposed and matched sham-treated males. ESTR mutation frequency was also established in sperm and blood samples taken from male mice exposed to 1 Gy of acute X-rays. The frequency of ESTR mutation in DNA samples extracted from blood of mice exposed to magnetic fields did not significantly differ from that in sham-treated controls. However, there was a marginally significant increase in mutation frequency in sperm but this was not dose-dependent. In contrast, acute exposure X-rays led to significant increases in mutation frequency in sperm and blood of exposed males. The results of our study suggest that, within the range of doses analyzed here, the in vivo mutagenic effects of ELF magnetic fields are likely to be minor if not negligible.

The effects of extremely low frequency magnetic fields on mutation induction in mice

International Nuclear Information System (INIS)

Wilson, James W.; Haines, Jackie; Sienkiewicz, Zenon; Dubrova, Yuri E.

2015-01-01

Highlights: • The effects of 50 Hz magnetic fields on mutation induction in mice were analyzed. • The frequency of ESTR mutation was established in sperm and blood. • Exposure to 10–300 μT for 2 and 15 h did not result in mutation induction. • Mutagenic effects of 50 Hz magnetic fields are likely to be negligible. - Abstract: The growing human exposure to extremely low frequency (ELF) magnetic fields has raised a considerable concern regarding their genotoxic effects. The aim of this study was to evaluate the in vivo effects of ELF magnetic fields irradiation on mutation induction in the germline and somatic tissues of male mice. Seven week old BALB/c × CBA/Ca F 1 hybrid males were exposed to 10, 100 or 300 μT of 50 Hz magnetic fields for 2 or 15 h. Using single-molecule PCR, the frequency of mutation at the mouse Expanded Simple Tandem Repeat (ESTR) locus Ms6-hm was established in sperm and blood samples of exposed and matched sham-treated males. ESTR mutation frequency was also established in sperm and blood samples taken from male mice exposed to 1 Gy of acute X-rays. The frequency of ESTR mutation in DNA samples extracted from blood of mice exposed to magnetic fields did not significantly differ from that in sham-treated controls. However, there was a marginally significant increase in mutation frequency in sperm but this was not dose-dependent. In contrast, acute exposure X-rays led to significant increases in mutation frequency in sperm and blood of exposed males. The results of our study suggest that, within the range of doses analyzed here, the in vivo mutagenic effects of ELF magnetic fields are likely to be minor if not negligible

Elimination of Spurious Fractional Charges in Dissociating Molecules by Correcting the Shape of Approximate Kohn-Sham Potentials.

Science.gov (United States)

Komsa, Darya N; Staroverov, Viktor N

2016-11-08

Standard density-functional approximations often incorrectly predict that heteronuclear diatomic molecules dissociate into fractionally charged atoms. We demonstrate that these spurious charges can be eliminated by adapting the shape-correction method for Kohn-Sham potentials that was originally introduced to improve Rydberg excitation energies [ Phys. Rev. Lett. 2012 , 108 , 253005 ]. Specifically, we show that if a suitably determined fraction of electron charge is added to or removed from a frontier Kohn-Sham orbital level, the approximate Kohn-Sham potential of a stretched molecule self-corrects by developing a semblance of step structure; if this potential is used to obtain the electron density of the neutral molecule, charge delocalization is blocked and spurious fractional charges disappear beyond a certain internuclear distance.

Evaluation of the efficacy of zoledronic acid and amifostine on radiation induced bone loss in mice

Energy Technology Data Exchange (ETDEWEB)

Kim, Jin Wook; Lee, Sueum; Kang, Sohi; Moon, Cahng Jong; Kim, Jong Choon; Kim, Sung Ho [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of); Jung, Uhee; Jo, Sung Kee [Advanced Radiation Technology Institute, Jeungeup (Korea, Republic of); Jang, Jong Sik [College of Ecology and Environmental Science, Kyungpook National University, Sangju (Korea, Republic of)

2016-09-15

This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Treatment of ZA (100 μg·kg{sup -1}·week{sup -1}) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. The results indicate that ZA can prevent radiation-induced bone loss in mice.

Reduced spatial learning in mice infected with the nematode, Heligmosomoides polygyrus.

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Kavaliers, M; Colwell, D D

1995-06-01

Parasite modification of host behaviour influences a number of critical responses, but little is known about the effects on host spatial abilities. This study examined the effects of infection with the intestinal trichostrongylid nematode, Heligmosomoides polygyrus, on spatial water maze learning by male laboratory mice, Mus musculus. In this task individual mice had to learn the spatial location of a submerged hidden platform using extramaze visual cues. Determinations of spatial performance were made on day 19 post-infection with mice that had been administered either 50 or 200 infective larvae of H. polygyrus. The infected mice displayed over 1 day of testing (6 blocks of 4 trials) significantly poorer acquisition and retention of the water maze task than either sham-infected or control mice, with mice that had received 200 infective larvae displaying significantly poorer spatial performance than individuals receiving 50 larvae. The decrease in spatial learning occurred in the absence of either any symptoms of illness and malaise, or any evident motor, visual and motivational impairments. It is suggested that in this single host system the parasitic infection-induced decrease in spatial learning arises as a side-effect of the host's immunological and neuromodulatory responses and represents a fitness cost of response to infection.

Aqueous Extract of Black Maca (Lepidium meyenii) on Memory Impairment Induced by Ovariectomy in Mice.

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Rubio, Julio; Qiong, Wang; Liu, Xinmin; Jiang, Zhen; Dang, Haixia; Chen, Shi-Lin; Gonzales, Gustavo F

2011-01-01

The present study aims to test two different doses of aqueous extract of black maca on learning and memory in ovariectomized (OVX) mice and their relation with malonalehyde (MDA), acetylcholinesterase (Ache) and monoamine oxidase (MAO) brain levels. Female mice were divided into five groups: (i) naive (control), (ii) sham, (iii) OVX mice and OVX mice treated with (iv) 0.50 g kg(-1) and (v) 2.00 g kg(-1) black maca. Mice were orally treated with distilled water or black maca during 35 days starting 7 days after surgery. Memory and learning were assessed using the water Morris maze (from day 23-27) and the step-down avoidance test (days 34 and 35). At the end of each treatment, mice were sacrificed by decapitation and brains were dissected out for MDA, Ache and MAO determinations. Black maca (0.5 and 2.0 g/kg) increased step-down latency when compared to OVX control mice. Black maca decreased MDA and Ache levels in OVX mice; whereas, no differences were observed in MAO levels. Finally, black maca improved experimental memory impairment induced by ovariectomy, due in part, by its antioxidant and Ache inhibitory activities.

Cholinergic degeneration is associated with increased plaque deposition and cognitive impairment in APPswe/PS1dE9 mice

DEFF Research Database (Denmark)

Laursen, Bettina; Mørk, Arne; Plath, Niels

2013-01-01

mice was not due to a more extensive cholinergic degeneration since the reduction in choline acetyltransferase activity was similar following SAP treatment in APP/PS1 mice and Wt. Interestingly, plaque load was significantly increased in SAP treated APP/PS1 mice relative to sham lesioned APP/PS1 mice....... Additionally, APP/PS1 mice treated with SAP showed a tendency towards an increased level of soluble and insoluble Aß1-40 and Aß1-42 measured in brain tissue homogenate. Our results suggest that the combination of cholinergic degeneration and Aß overexpression in the APP/PS1 mouse model results in cognitive...... decline and accelerated plaque burden. SAP treated APP/PS1 mice might thus constitute an improved model of Alzheimer's disease-like neuropathology and cognitive deficits compared to the conventional APP/PS1 model without selective removal of basal forebrain cholinergic neurons....

Does a single session of electroconvulsive therapy alter the neural response to emotional faces in depression? A randomised sham-controlled functional magnetic resonance imaging study.

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Miskowiak, Kamilla W; Kessing, Lars V; Ott, Caroline V; Macoveanu, Julian; Harmer, Catherine J; Jørgensen, Anders; Revsbech, Rasmus; Jensen, Hans M; Paulson, Olaf B; Siebner, Hartwig R; Jørgensen, Martin B

2017-09-01

Negative neurocognitive bias is a core feature of major depressive disorder that is reversed by pharmacological and psychological treatments. This double-blind functional magnetic resonance imaging study investigated for the first time whether electroconvulsive therapy modulates negative neurocognitive bias in major depressive disorder. Patients with major depressive disorder were randomised to one active ( n=15) or sham electroconvulsive therapy ( n=12). The following day they underwent whole-brain functional magnetic resonance imaging at 3T while viewing emotional faces and performed facial expression recognition and dot-probe tasks. A single electroconvulsive therapy session had no effect on amygdala response to emotional faces. Whole-brain analysis revealed no effects of electroconvulsive therapy versus sham therapy after family-wise error correction at the cluster level, using a cluster-forming threshold of Z>3.1 ( p2.3; pelectroconvulsive therapy-induced changes in parahippocampal and superior frontal responses to fearful versus happy faces as well as in fear-specific functional connectivity between amygdala and occipito-temporal regions. Across all patients, greater fear-specific amygdala - occipital coupling correlated with lower fear vigilance. Despite no statistically significant shift in neural response to faces after a single electroconvulsive therapy session, the observed trend changes after a single electroconvulsive therapy session point to an early shift in emotional processing that may contribute to antidepressant effects of electroconvulsive therapy.

Effect of single and fractionated x-irradiation on maze learning ability of mice

International Nuclear Information System (INIS)

Aoyama, Takashi; Norimura, Toshiyuki; Nakamura, Takeshi; Yoshikawa, Isao

1976-01-01

Fifty-six-day-old male ddk mice at the starting of the investigation were used as subjects through the experiment for 64 weeks. After 15 days' preliminary training, and 16 times of weekly trial training using complete maze, 15 mice received a single 224 rads of x-rays (S group), another 15 mice received two 112 rads spaced two weeks apart (F group) and another 15 mice were sham-irradiated (Control group). Then those mice were tested on the multiple T-maze with nine-choice points and change of performance was observed in terms of errorchoices by giving one test trial a week. We introduced the concept of ''confusional trials'' as an index for surmising to what extent mice failed to exhibit good maze learning habits. In the results, the F group showed significantly worse performance than the two other groups at early stages, opposite to it the S group exhibited the same, but at late stages after irradiation. The worse performance of F group should be considered to be due to the psychological after-effect to fractionated irradiation and that for S group could be assumed to be due to the acceleration of aging by the irradiation. (auth.)

Silent Speech A Reflection on the body language in Shams's ghazals

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Mohammad Reza Hashemi

2014-11-01

Full Text Available Abstract Literature as a verbal medium containing human characters is full of non verbal signs such as body language. Use of this indicational language in the Shams's sonnets is considerable. Mowlavi in this work, mostly for preserving sanctum of character, specially Shams, has described his gestures in various position, utilizing of body language in symbolic way. So, taking care of them, one can understand the response of addresser into addressee and assess his place and sense into him on the basis of discourse approach.    This article consists of an introduction and three parts. Introduction and the part of problem statement involves defining the problem, questions, hypotheses and background of research. After introduction, the theoretical basis for research has been mentioned. In this section, we discussed non-verbal signs and body language, researchers’ ideas about the role of body language in literature and kinds of nonverbal signs. Then we spoke about methods of applying body language. For this purpose, non-verbal signs including a kind of visual, phonetic and symptoms related to the physical distance have been studied and then semantic range and frequency of repetition of each item have been determined. Main part of this article is dedicated to analyzing the data obtained from ghazals. At this stage of the research, studying the body language of Shams’s ghazals, different movements and the meaning of each, every effects related to the body language approach has been collected based on author’s linguistic talent. Then the list of gestures and their meanings, in terms of semiotics, has been prepared. It is to be said that due to the multiplicity of samples and the limitations of paper, just some examples of usage of body language in Mowlavi's verses has been analyzed. To learn more about that, readers can see final notes listed. In the next stage, by drawing a diagram, the frequencies of these signs used in the

High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

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Gwon, Do Hyeong; Hwang, Tae Woong; Ro, Ju-Ye; Kang, Yoon-Joong; Jeong, Jin Young; Kim, Do-Kyung; Lim, Kyu; Kim, Dong Woon; Choi, Dae Eun; Kim, Jwa-Jin

2017-09-30

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham ( n = 10), fat-1 sham ( n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI ( n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

Effects of Salvia miltiorrhiza extract with supplemental liquefied calcium on osteoporosis in calcium-deficient ovariectomized mice.

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Park, Bongkyun; Song, Hae Seong; Kwon, Jeong Eun; Cho, Se Min; Jang, Seon-A; Kim, Mi Yeon; Kang, Se Chan

2017-12-20

Extracts from Salvia miltiorrhiza Bunge have been used in traditional Asian medicine to treat coronary heart disease, chronic renal failure, atherosclerosis, myocardial infraction, angina pectoris, myocardial ischemia, dysmenorrheal, neurasthenic insomnia, liver fibrosis and cirrhosis. The aim of the study was to investigate the anti-RANK signal effect of the combination of S.miltiorrhiza Bunge (SME) and liquefied calcium (LCa) supplement with ovariectomized (OVX-SML) mice, a osteoporosis animal model. Results were compared to 17β-estradiol (E 2 ) treatment. A total of 70 female ICR strain mice (7 weeks) were randomly divided into 10 groups with 7 mice in each group as follows: (1) sham-operated control mice (sham) received daily oral phosphate-buffered-saline (PBS) of equal volumes through oral administration. (2) OVX mice received a daily oral administration of PBS (OVX). (3) OVX mice treated daily with 50 mg/kg b.w./ day of SME (4) with 100 mg/kg b.w./day of SME or (5) with 200 mg/kg b.w./day of SME via oral administration. (6) OVX mice treated daily with 50 mg/kg b.w./day of SML (7) with 100 mg/kg b.w./day of SML or (8) with 200 mg/kg b.w./day of SML via oral administration. (9) OVX mice treated daily with 10 ml/kg b.w./day of LCa (10) OVX mice received i.p. injections of 17β-estradiol (E 2 ) (0.1 mg/kg b.w./day) three times per week for 12 weeks. micro-CT analysis revealed that oral administration of SML inhibited tibial bone loss, sustained trabecular bone state, and ameliorated bone biochemical markers. In addition, SML administration compared to SEM and LCa reduced serum levels of RANKL, osteocalcin and BALP through increased serum levels of OPG and E 2 in OVX mice. SML also had more beneficial effects on protection of estrogen-dependent bone loss through blocking expression of TRAF6 and NFTAc1 and produces cathepsin K and calcitonin receptor to develop osteoclast differentiation. These data suggest that S. miltiorrhiza Bunge combined with

Adaptive local basis set for Kohn–Sham density functional theory in a discontinuous Galerkin framework I: Total energy calculation

International Nuclear Information System (INIS)

Lin Lin; Lu Jianfeng; Ying Lexing; Weinan, E

2012-01-01

Kohn–Sham density functional theory is one of the most widely used electronic structure theories. In the pseudopotential framework, uniform discretization of the Kohn–Sham Hamiltonian generally results in a large number of basis functions per atom in order to resolve the rapid oscillations of the Kohn–Sham orbitals around the nuclei. Previous attempts to reduce the number of basis functions per atom include the usage of atomic orbitals and similar objects, but the atomic orbitals generally require fine tuning in order to reach high accuracy. We present a novel discretization scheme that adaptively and systematically builds the rapid oscillations of the Kohn–Sham orbitals around the nuclei as well as environmental effects into the basis functions. The resulting basis functions are localized in the real space, and are discontinuous in the global domain. The continuous Kohn–Sham orbitals and the electron density are evaluated from the discontinuous basis functions using the discontinuous Galerkin (DG) framework. Our method is implemented in parallel and the current implementation is able to handle systems with at least thousands of atoms. Numerical examples indicate that our method can reach very high accuracy (less than 1 meV) with a very small number (4–40) of basis functions per atom.

Development of heart failure is independent of K+ channel-interacting protein 2 expression

DEFF Research Database (Denmark)

Speerschneider, Tobias; Grubb, Søren; Metoska, Artina

2013-01-01

of the transient outward K(+) current (Ito). We aim to investigate the possible significance of a changed KChIP2 expression on the development of HF and proarrhythmia. Transverse aortic constrictions (TAC) and sham operations were performed in wild-type (WT) and KChIP2(-/-) mice. Echocardiography was performed......(-/-) mice. Ventricular protein expression of KChIP2 was reduced by 70% after 10 weeks TAC in WT mice. The amplitudes of the J and T waves were enlarged in KChIP2(-/-) control mice. Ventricular effective refractory period, RR, QRS and QT intervals were longer in mice with HF compared to sham-operated mice...... of either genotype. Pacing-induced ventricular tachycardia (VT) was observed in 5/10 sham-operated WT mice compared with 2/10 HF WT mice with HF. Interestingly, and contrary to previously published data, sham-operated KChIP2(-/-) mice were resistant to pacing-induced VT resulting in only 1/10 inducible mice...

Syngeneic B16F10 Melanoma Causes Cachexia and Impaired Skeletal Muscle Strength and Locomotor Activity in Mice

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Fabrício A. Voltarelli

2017-09-01

Full Text Available Muscle wasting has been emerging as one of the principal components of cancer cachexia, leading to progressive impairment of work capacity. Despite early stages melanomas rarely promotes weight loss, the appearance of metastatic and/or solid tumor melanoma can leads to cachexia development. Here, we investigated the B16F10 tumor-induced cachexia and its contribution to muscle strength and locomotor-like activity impairment. C57BL/6 mice were subcutaneously injected with 5 × 104 B16F10 melanoma cells or PBS as a Sham negative control. Tumor growth was monitored during a period of 28 days. Compared to Sham mice, tumor group depicts a loss of skeletal muscle, as well as significantly reduced muscle grip strength and epididymal fat mass. This data are in agreement with mild to severe catabolic host response promoted by elevated serum tumor necrosis factor-alpha (TNF-α, interleukin-6 (IL-6 and lactate dehydrogenase (LDH activity. Tumor implantation has also compromised general locomotor activity and decreased exploratory behavior. Likewise, muscle loss, and elevated inflammatory interleukin were associated to muscle strength loss and locomotor activity impairment. In conclusion, our data demonstrated that subcutaneous B16F10 melanoma tumor-driven catabolic state in response to a pro-inflammatory environment that is associated with impaired skeletal muscle strength and decreased locomotor activity in tumor-bearing mice.

Effects of Hot Water Extracts from Polygonum multiflorum on Ovariectomy Induced Osteopenia in Mice

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Yun-Ho Hwang

2016-01-01

Full Text Available Polygonum multiflorum (PM, a traditional Chinese medicine, is used to treat various diseases including nonalcoholic fatty liver disease and hyperlipidemia. However, the influence of PM on osteoporosis in animals is unclear. The present study investigated the antiosteoporotic effect of PM on bone mass in ovariectomized (OVX mice and its possible mechanism of action. Twenty-five female C3H/HeN mice were divided into five groups of five mice as follows. Sham-operated control mice received daily oral gavage of an equal volume of water, and OVX mice received daily oral gavage of water or an injection of β-estradiol or PM for 6 weeks. Administration of PM significantly suppressed body weight and organs weight and increased weight and length of bone compared with the OVX group. Treatment with PM reversed osteopenia in OVX mice, thereby improving the bone morphometric parameters. Moreover, histological analysis using hematoxylin and eosin staining showed that PM inhibited OVX-induced bone loss. Serum estradiol and bone alkaline phosphatase levels were significantly decreased in the OVX group, with the levels increasing with PM treatment. In addition, tartrate-resistant acid phosphatase activity was inhibited by PM in OVX mice. These results suggest that PM is effective in preventing bone loss in OVX mice.

Selective Toll-Like Receptor 4 Antagonists Prevent Acute Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Mice.

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Okada, Takeshi; Kawakita, Fumihiro; Nishikawa, Hirofumi; Nakano, Fumi; Liu, Lei; Suzuki, Hidenori

2018-05-31

There are no direct evidences showing the linkage between Toll-like receptor 4 (TLR4) and blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). The purpose of this study was to examine if selective blockage of TLR4 prevents BBB disruption after SAH in mice and if the TLR4 signaling involves mitogen-activated protein kinases (MAPKs). One hundred and fifty-one C57BL/6 male mice underwent sham or endovascular perforation SAH operation, randomly followed by an intracerebroventricular infusion of vehicle or two dosages (117 or 585 ng) of a selective TLR4 antagonist IAXO-102 at 30 min post-operation. The effects were evaluated by survival rates, neurological scores, and brain water content at 24-72 h and immunoglobulin G immunostaining and Western blotting at 24 h post-SAH. IAXO-102 significantly prevented post-SAH neurological impairments, brain edema, and BBB disruption, resulting in improved survival rates. IAXO-102 also significantly suppressed post-SAH activation of a major isoform of MAPK p46 c-Jun N-terminal kinase (JNK) and matrix metalloproteinase-9 as well as periostin induction and preserved tight junction protein zona occludens-1. Another selective TLR4 antagonist TAK-242, which has a different binding site from IAXO-102, also showed similar effects to IAXO-102. This study first provided the evidence that TLR4 signaling is involved in post-SAH acute BBB disruption and that the signaling is mediated at least partly by JNK activation. TLR4-targeted therapy may be promising to reduce post-SAH morbidities and mortalities.

Cancer causes increased mortality and is associated with altered apoptosis in murine sepsis.

Science.gov (United States)

Fox, Amy C; Robertson, Charles M; Belt, Brian; Clark, Andrew T; Chang, Katherine C; Leathersich, Ann M; Dominguez, Jessica A; Perrone, Erin E; Dunne, W Michael; Hotchkiss, Richard S; Buchman, Timothy G; Linehan, David C; Coopersmith, Craig M

2010-03-01

Whereas most septic patients have an underlying comorbidity, most animal models of sepsis use mice that were healthy before the onset of infection. Malignancy is the most common comorbidity associated with sepsis. The purpose of this study was to determine whether mice with cancer have a different response to sepsis than healthy animals. Prospective, randomized controlled study. Animal laboratory in a university medical center. C57Bl/6 mice. Animals received a subcutaneous injection of either 250,000 cells of the transplantable pancreatic adenocarcinoma cell line Pan02 (cancer) or phosphate-buffered saline (healthy). Three weeks later, mice given Pan02 cells had reproducible, nonmetastatic tumors. Both groups of mice then underwent intratracheal injection of either Pseudomonas aeruginosa (septic) or 0.9% NaCl (sham). Animals were killed 24 hrs postoperatively or followed-up 7 days for survival. Mice with cancer and healthy mice appeared similar when subjected to sham operation, although cancer animals had lower levels of T- and B-lymphocyte apoptosis. Septic mice with cancer had increased mortality compared to previously healthy septic mice subjected to the identical injury (52% vs. 28%; p = .04). This was associated with increased bacteremia but no difference in local pulmonary infection. Septic mice with cancer also had increased intestinal epithelial apoptosis. Although sepsis induced an increase in T- and B-lymphocyte apoptosis in all animals, septic mice with cancer had decreased T- and B-lymphocyte apoptosis compared to previously healthy septic mice. Serum and pulmonary cytokines, lung histology, complete blood counts, and intestinal proliferation were similar between septic mice with cancer and previously healthy septic mice. When subjected to the same septic insult, mice with cancer have increased mortality compared to previously healthy animals. Decreased systemic bacterial clearance and alterations in intestinal epithelial and lymphocyte apoptosis may

Are all placebo effects equal? Placebo pills, sham acupuncture, cue conditioning and their association.

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Jian Kong

Full Text Available Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol, sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for "placebo responders." However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non

Structure of the optimized effective Kohn-Sham exchange potential and its gradient approximations

International Nuclear Information System (INIS)

Gritsenko, O.; Van Leeuwen, R.; Baerends, E.J.

1996-01-01

An analysis of the structure of the optimized effective Kohn-Sham exchange potential v, and its gradient approximations is presented. The potential is decomposed into the Slater potential v s and the response of v s to density variations, v resp . The latter exhibits peaks that reflect the atomic shell structure. Kohn-Sham exchange potentials derived from current gradient approaches for the exchange energy are shown to be quite reasonable for the Slater potential, but they fail to approximate the response part, which leads to poor overall potentials. Improved potentials are constructed by a direct fit of v x with a gradient-dependent Pade approximant form. The potentials obtained possess proper asymptotic and scaling properties and reproduce the shell structure of the exact v x . 44 refs., 7 figs., 4 tabs

Kohn-Sham density functional theory for quantum wires in arbitrary correlation regimes

NARCIS (Netherlands)

Malet, F.; Mirtschink, A.P.; Cremon, J. C.; Reimann, S. M.; Gori Giorgi, P.

2013-01-01

We use the exact strong-interaction limit of the Hohenberg-Kohn energy density functional to construct an approximation for the exchange-correlation term of the Kohn-Sham approach. The resulting exchange-correlation potential is able to capture the features of the strongly correlated regime without

Radiation-induced life shortening in neonatally thymectomized germ-free mice

International Nuclear Information System (INIS)

Anderson, R.E.; Howarth, J.L.; Troup, G.M.

1980-01-01

Radiation in sufficient amounts is carcinogenic, immunosuppressive, and results in a reduced life span. Similar consequences follow neonatal thymectomy (nTx) in some strains of rodents. The tumorigenic effects of irradiation appear to be partly mediated via suppression of the thymus-dependent portion of the immune response. Our purpose was to determine whether a similar relationship exists for radiation-induced accelerated aging. Female germ-free Charles River mice had neonatal or sham thymectomies within 24 hours of birth. Half of each group was exposed to 700 rads at 6 weeks of age. When mice with histologically malignant tumors were excluded, the combined life-shortening effects of nTx and irradiation were less pronounced than the sum of the individual effects. This suggests that some of the decreased longevity associated with irradiation may be mediated by T-cell injury

Role of the vomeronasal system in intersexual attraction in female mice.

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Martínez-Ricós, J; Agustín-Pavón, C; Lanuza, E; Martínez-García, F

2008-05-02

Although it is generally accepted that rodents' sociosexual behavior relies mainly on chemosignals, the specific roles played by the vomeronasal and olfactory systems in detecting these signals are presently unclear. This work reports the results of three experiments aimed at clarifying the role of the vomeronasal system on gender recognition and intersexual attraction, by analyzing the effects of lesions of the accessory olfactory bulbs (AOB) in chemically naïve female mice. The first experiment demonstrates that lesions of the AOB abolish the preference that females show for male-soiled bedding in tests in which the females can contact the bedding, thus having access to both volatile and involatile male chemosignals. The second experiment shows that airborne male-derived chemosignals are not attractive to intact, chemically naïve females but tend to be preferentially explored by females whose AOB has been lesioned. However, repeated exposure to male-soiled bedding has opposite effects in sham-operated and AOB-lesioned female mice. Whereas after this experience sham-operated females show an (acquired) attraction toward male airborne chemosignals, in AOB-lesioned females the same experience makes male-derived volatiles aversive. Finally, in the third experiment we have confirmed that our AOB-lesioned females are able to detect urine-borne male odorants, as well as to discriminate them from the synthetic terpene geraniol. These findings strongly suggest that in mice, the involatile male sexual pheromone that is intrinsically attractive is detected by the vomeronasal system of the females. In addition, the repeated experience of females with male-soiled bedding would probably allow the association of this pheromone, acting as unconditioned stimulus, with olfactory stimuli (odorants) that therefore would become conditioned attractors to the females.

Role of heat shock transcription factor 1(HSF1)-upregulated macrophage in ameliorating pressure overload-induced heart failure in mice.

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Du, Peizhao; Chang, Yaowei; Dai, Fangjie; Wei, Chunyan; Zhang, Qi; Li, Jiming

2018-08-15

In order to explore the role of macrophages in HSF1-mediated alleviation of heart failure, mice model of pressure overload-induced heart failure was established using transverse aortic constriction (TAC). Changes in cardiac function and morphology were studied in TAC and SHAM groups using ultrasonic device, tissue staining, electron microscopy, real-time quantitative polymerase chain reaction (RT-QPCR), and Western blotting. We found that mice in the TAC group showed evidence of impaired cardiac function and aggravation of fibrosis on ultrasonic and histopathological examination when compared to those in the SHAM group. The expressions of HSF1, LC3II/LC3I, Becline-1 and HIF-1, as well as autophagosome formation in TAC group were greater than that in SHAM group. On sub-group analyses in the TAC group, improved cardiac function and alleviation of fibrosis was observed in the HSF1 TG subgroup as compared to that in the wild type subgroup. Expressions of LC3II/LC3I, Becline-1 and HIF-1, too showed an obvious increase; and increased autophagosome formation was observed on electron microscopy. Opposite results were observed in the HSF1 KO subgroup. These results collectively suggest that in the pressure overload heart failure model, HSF1 promoted formation of macrophages by inducing upregulation of HIF-1 expression, through which heart failure was ameliorated. Copyright © 2018 Elsevier B.V. All rights reserved.

Sustained Weight Loss with Vagal Nerve Blockade but Not with Sham: 18-Month Results of the ReCharge Trial

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Scott A. Shikora

2015-01-01

Full Text Available Background/Objectives. Vagal block therapy (vBloc is effective for moderate to severe obesity at one year. Subjects/Methods. The ReCharge trial is a double-blind, randomized controlled clinical trial of 239 participants with body mass index (BMI of 40 to 45 kg/m or 35 to 40 kg/m with one or more obesity-related conditions. Interventions were implantation of either vBloc or Sham devices and weight management counseling. Mixed models assessed percent excess weight loss (%EWL and total weight loss (%TWL in intent-to-treat analyses. At 18 months, 142 (88% vBloc and 64 (83% Sham patients remained enrolled in the study. Results. 18-month weight loss was 23% EWL (8.8% TWL for vBloc and 10% EWL (3.8% TWL for Sham (P<0.0001. vBloc patients largely maintained 12-month weight loss of 26% EWL (9.7% TWL. Sham regained over 40% of the 17% EWL (6.4% TWL by 18 months. Most weight regain preceded unblinding. Common adverse events of vBloc through 18 months were heartburn/dyspepsia and abdominal pain; 98% of events were reported as mild or moderate and 79% had resolved. Conclusions. Weight loss with vBloc was sustained through 18 months, while Sham regained weight between 12 and 18 months. vBloc is effective with a low rate of serious complications.

Repetitive transcranial magnetic stimulation and transcranial direct-current stimulation in neuropathic pain due to radiculopathy: a randomized sham-controlled comparative study.

Science.gov (United States)

Attal, Nadine; Ayache, Samar S; Ciampi De Andrade, Daniel; Mhalla, Alaa; Baudic, Sophie; Jazat, Frédérique; Ahdab, Rechdi; Neves, Danusa O; Sorel, Marc; Lefaucheur, Jean-Pascal; Bouhassira, Didier

2016-06-01

No study has directly compared the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in neuropathic pain (NP). In this 2-centre randomised double-blind sham-controlled study, we compared the efficacy of 10-Hz rTMS and anodal 2-mA tDCS of the motor cortex and sham stimulation contralateral to the painful area (3 daily sessions) in patients with NP due to lumbosacral radiculopathy. Average pain intensity (primary outcome) was evaluated after each session and 5 days later. Secondary outcomes included neuropathic symptoms and thermal pain thresholds for the upper limbs. We used an innovative design that minimised bias by randomly assigning patients to 1 of 2 groups: active rTMS and tDCS or sham rTMS and tDCS. For each treatment group (active or sham), the order of the sessions was again randomised according to a crossover design. In total, 51 patients were screened and 35 (51% women) were randomized. Active rTMS was superior to tDCS and sham in pain intensity (F = 2.89 and P = 0.023). Transcranial direct-current stimulation was not superior to sham, but its analgesic effects were correlated to that of rTMS (P = 0.046), suggesting common mechanisms of action. Repetitive transcranial magnetic stimulation lowered cold pain thresholds (P = 0.04) and its effect on cold pain was correlated with its analgesic efficacy (P = 0.006). However, rTMS had no impact on individual neuropathic symptoms. Thus, rTMS is more effective than tDCS and sham in patients with NP due to lumbosacral radiculopathy and may modulate the sensory and affective dimensions of pain.

Tritium toxicity on postnatally developing mice testes: a qualitative and quantitative evaluation

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Bhatia, A.L.

1982-01-01

The present study is an attempt to evaluate the possible radiobiological effects of tritiated water (HTO) on the testes of Swiss albino mice during postnatal development. Mice were continuously irradiated with different doses providing 46, 93 and 185 kBq of HTO per ml drinking water (after a priming injection) from day 1 after brith up to 6 weeks of age. Qualitative and quantitative studies were made at 6 weeks old mice testes and were compared with the sham-irradiated controls. A dose-dependent damage is noticed in the testes in the form of various radiopathological lesions such as intertubular edema, necrotic and pycnotic cells at various stages, mild cytoplasmic vacuolation, fibrosis, sclerosis, cellular edema etc. The number of various germ cells at their different phases were greatly reduced. 185 kBq/ml affect severely the spermatogonia and spermatid populations. The primary spermatocyte level was maintained at the range 64 +- 3.5%

Tritium toxicity on postnatally developing mice testes: a qualitative and quantitative evaluation

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Bhatia, A.L. (Rajasthan Univ., Jaipur (India). Radiation Biology Lab.)

1982-11-01

The present study is an attempt to evaluate the possible radiobiological effects of tritiated water (HTO) on the testes of Swiss albino mice during postnatal development. Mice were continuously irradiated with different doses providing 46, 93 and 185 kBq of HTO per ml drinking water (after a priming injection) from day 1 after brith up to 6 weeks of age. Qualitative and quantitative studies were made at 6 weeks old mice testes and were compared with the sham-irradiated controls. A dose-dependent damage is noticed in the testes in the form of various radiopathological lesions such as intertubular edema, necrotic and pycnotic cells at various stages, mild cytoplasmic vacuolation, fibrosis, sclerosis, cellular edema etc. The number of various germ cells at their different phases were greatly reduced. 185 kBq/ml affect severely the spermatogonia and spermatid populations. The primary spermatocyte level was maintained at the range 64 +- 3.5%.

Study Of The Effect Of Heroin Used In Iran, On Spermatogenesis Changes And Their Development In Balb/C Mice

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Fazelipour S

2005-05-01

Full Text Available Background: Heroin is one of the opiates which is used, as the most addictive drugs, in Iran. Considering the damaging effects of these drugs on the health of opiate addicts, investigation on the effects of heroin used in Iran, on male genital indicators including daily sperm production and its development, which has an essential role in fertility, seems to be necessary. Materials and Methods: A total of 70 Bulb/c mature male mice, were divided into 5 groups of control, [intact (n=10, sham I (n=10 sham II (n=10] and experimental groups [I (n=20, II (n=20], and 50 days after addiction to heroin (50 mg/kg via intra peritoneal injection (IP, 6 mice from each groups were selected and after euthenizing, the testes and epididymes were removed. The rate of daily sperm production (DSP, epididymic sperm preservation (ESP and the rate of sperm motility were measured accurately. Results: In the study of the effect of heroin on daily sperm production and sperm preservation between the control and experimental groups, no significant differences were observed. The effect of heroin on sperm motility between control and experimental groups, the difference were significant (P<0/05. Conclusions: In this survey, it was indicated that, the heroin used in Iran, causes a decrease in healthy sperms of mice their motility, and consequently can affect on genital indicators.

Muscle changes can account for bone loss after botulinum toxin injection.

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Manske, Sarah L; Boyd, Steven K; Zernicke, Ronald F

2010-12-01

Studies to date have assumed that botulinum toxin type A (BTX) affects bone indirectly, through its action on muscle. We hypothesized that BTX has no discernable effect on bone morphometry, independent of its effect on muscle. Therefore, we investigated whether BTX had an additional effect on bone when combined with tenotomy compared to tenotomy in isolation. Female BALB/c mice (n = 73) underwent one of the following procedures in the left leg: BTX injection and Achilles tenotomy (BTX-TEN), BTX injection and sham surgery (BTX-sham), Achilles tenotomy (TEN), or sham surgery (sham). BTX groups were injected with 20 μL of BTX (1 U/100 g) in the posterior lower hindlimb. At 4 weeks, muscle cross-sectional area (MCSA) and tibial bone morphometry were assessed using micro-CT. Each treatment, other than sham, resulted in significant muscle and bone loss (P properties. We found that BTX injection resulted in more adverse muscle and bone effects than tenotomy and that effects were amplified when the procedures were combined. However, between-group differences in bone could be accounted for by MCSA. We conclude that any independent effect of BTX on bone morphometry is likely small or negligible compared with the effect on muscle.

Honokiol Improves Liver Steatosis in Ovariectomized Mice

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Yeon-Hui Jeong

2018-01-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common liver disease, and is associated with the development of metabolic syndrome. Postmenopausal women with estrogen deficiency are at a higher risk of progression to NAFLD. Estrogen has a protective effect against the progression of the disease. Currently, there are no safe and effective treatments for these liver diseases in postmenopausal women. Honokiol (Ho, a bioactive natural product derived from Magnolia spp, has anti-inflammatory, anti-angiogenic, and anti-oxidative properties. In our study, we investigated the beneficial effects of Ho on NAFLD in ovariectomized (OVX mice. We divided the mice into four groups, as follows: SHAM, OVX, OVX+β-estradiol (0.4 mg/kg of bodyweight, and OVX+Ho (50 mg/kg of diet. Mice were fed diets with/without Ho for 12 weeks. The bodyweight, epidermal fat, and weights of liver tissue were lower in the OVX group than in the other groups. Ho improved hepatic steatosis and reduced proinflammatory cytokine levels. Moreover, Ho markedly downregulated plasma lipid levels. Our results indicate that Ho ameliorated OVX-induced fatty liver and inflammation, as well as associated lipid metabolism. These findings suggest that Ho may be hepatoprotective against NAFLD in postmenopausal women.

Onset of behavioral effects in mice exposed to 10 Gy Co-60 radiation

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Maier, D.M.; Landauer, M.R.

1990-01-01

The effects of 10 Gray (Gy) Co-60 radiation on social behavior, locomotor activity, and body weight were assessed in individually housed male Swiss-Webster mice. In experiment 1, aggressive behavior was evaluated prior to irradiation and for 7 d postirradiation by placing an untreated intruder in the irradiated or sham-irradiated resident's home cage for 5 min. Offensive aggressive behavior was not affected significantly by radiation until day 7 postirradiation, when attack latency increased, the frequency and duration of fighting decreased, and the frequency of bites, lunges, and chases decreased. Untreated intruder mice paired with irradiated resident mice showed a decrease in the duration of defensive upright postures and a decrease in the frequency of defensive upright postures, squeaks, and escapes on day 7 postirradiation. In experiment 2, locomotor activity and body weight were monitored for 7 d postirradiation. Body weight was decreased in irradiated mice beginning 4 d postirradiation. Locomotor activity was suppressed in irradiated animals 90 min after irradiation and remained depressed throughout the 7-d testing period. 25 refs

High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice

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Do Hyeong Gwon

2017-09-01

Full Text Available Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI. Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs from ω6-Polyunsaturated fatty acids (ω6-PUFAs without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt were divided into four groups: wt sham (n = 10, fat-1 sham (n = 10, wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15, and fat-1 IRI (n = 15. Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR. Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

Thioredoxin-1 attenuates sepsis-induced cardiomyopathy after cecal ligation and puncture in mice.

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Wilson, Rickesha L; Selvaraju, Vaithinathan; Lakshmanan, Rajesh; Thirunavukkarasu, Mahesh; Campbell, Jacob; McFadden, David W; Maulik, Nilanjana

2017-12-01

Sepsis is a leading cause of mortality among patients in intensive care units across the USA. Thioredoxin-1 (Trx-1) is an essential 12 kDa cytosolic protein that, apart from maintaining the cellular redox state, possesses multifunctional properties. In this study, we explored the possibility of controlling adverse myocardial depression by overexpression of Trx-1 in a mouse model of severe sepsis. Adult C57BL/6J and Trx-1 Tg/+ mice were divided into wild-type sham (WTS), wild-type cecal ligation and puncture (WTCLP), Trx-1 Tg/+ sham (Trx-1 Tg/+ S), and Trx-1 Tg/+ CLP groups. Cardiac function was evaluated before surgery, 6 and 24 hours after CLP surgery. Immunohistochemical and Western blot analysis were performed after 24 hours in heart tissue sections. Echocardiography analysis showed preserved cardiac function in the Trx-1 Tg/+ CLP group compared with the WTCLP group. Similarly, Western blot analysis revealed increased expression of Trx-1, heme oxygenase-1 (HO-1), survivin (an inhibitor of apoptosis [IAP] protein family), and decreased expression of thioredoxin-interacting protein (TXNIP), caspase-3, and 3- nitrotyrosine in the Trx-1 Tg/+ CLP group compared with the WTCLP group. Immunohistochemical analysis showed reduced 4-hydroxynonenal, apoptosis, and vascular leakage in the cardiac tissue of Trx-1 Tg/+ CLP mice compared with mice in the WTCLP group. Our results indicate that overexpression of Trx-1 attenuates cardiac dysfunction during CLP. The mechanism of action may involve reduction of oxidative stress, apoptosis, and vascular permeability through activation of Trx-1/HO-1 and anti-apoptotic protein survivin. Copyright © 2017 Elsevier Inc. All rights reserved.

Aqueous Extract of Black Maca (Lepidium meyenii on Memory Impairment Induced by Ovariectomy in Mice

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Julio Rubio

2011-01-01

Full Text Available The present study aims to test two different doses of aqueous extract of black maca on learning and memory in ovariectomized (OVX mice and their relation with malonalehyde (MDA, acetylcholinesterase (Ache and monoamine oxidase (MAO brain levels. Female mice were divided into five groups: (i naive (control, (ii sham, (iii OVX mice and OVX mice treated with (iv 0.50 g kg−1 and (v 2.00 g kg−1 black maca. Mice were orally treated with distilled water or black maca during 35 days starting 7 days after surgery. Memory and learning were assessed using the water Morris maze (from day 23–27 and the step-down avoidance test (days 34 and 35. At the end of each treatment, mice were sacrificed by decapitation and brains were dissected out for MDA, Ache and MAO determinations. Black maca (0.5 and 2.0 g/kg increased step-down latency when compared to OVX control mice. Black maca decreased MDA and Ache levels in OVX mice; whereas, no differences were observed in MAO levels. Finally, black maca improved experimental memory impairment induced by ovariectomy, due in part, by its antioxidant and Ache inhibitory activities.

Immuno-enhancement in tumor-bearing mice induced by whole body X-irradiation with 75 mGy

International Nuclear Information System (INIS)

Zhang Ying; Li Xiuyi; Gong Shouliang; Liu Shuzheng

2000-01-01

Objective: In present study the authors observed the effect of whole body irradiation (WBI) with 75 mGy X-rays on the immune function of tumor-bearing mice. Methods: Lewis lung carcinoma cells were implanted into the right thigh muscle of C57BL/6J mice. Ten days after tumor implantation, the tumor-bearing mice were administrated with 75 mGy X-rays WBI, then the mice were sacrificed 18 h after irradiation to detect the immune parameters including the spontaneous proliferation of thymocytes, the proliferative response of splenocytes to ConA and LPS, the cytotoxic activities of specific cytotoxic lymphocytes (CTL) and natural killer cells (NK), as well as lymphokine activated killer cells (LAK) in spleen. The methods the authors used were 3 H-TdR incorporation or release assay. Results: the immune parameters of exposed tumor-bearing mice were much higher than those of sham-irradiated tumor-bearing mice (P<0.01). Conclusion: These results suggested that low dose radiation (LDR) could enhance the immune function of tumor-bearing mice, which might be of practical significance in the prevention and therapy of cancer

EEG Neurofeedback for ADHD: Double-Blind Sham-Controlled Randomized Pilot Feasibility Trial

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Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara

2013-01-01

Objective: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. Method: Unmedicated 6- to 12-year-olds with "Diagnostic and Statistical Manual of…

Transcutaneous electrical nerve stimulator of 5000 Hz frequency provides better analgesia than that of 100 Hz frequency in mice muscle pain model

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Hung-Tsung Hsiao

2017-04-01

Full Text Available Transcutaneous electrical nerve stimulators (TENSs have been proved to be effective in muscle pain management for several decades. However, there is no consensus for the optimal TENS program. Previous research demonstrated that a 100 Hz TENS (L-TENS provided better analgesia than a conventional TENS ( 100 Hz TENS with a 100 Hz TENS. We used a 5000 Hz (5 kHz frequency TENS (M-TENS and an L-TENS to compare analgesic effect on a mice skin/muscle incision retraction model. Three groups of mice were used (sham, L-TENS, and M-TENS and applied with different TENS programs on Day 4 after the mice skin/muscle incision retraction model; TENS therapy was continued as 20 min/d for 3 days. Mice analgesic effects were measured via Von Frey microfilaments with the up–down method. After therapy, mice spinal cord dorsal horn and dorsal root ganglion (DRG were harvested for cytokine evaluation (tumor necrosis factor-α and interleukin-1β with the Western blotting method. Our data demonstrated that the M-TENS produced better analgesia than the L-TENS. Cytokine in the spinal cord or DRG all expressed lower than that of the sham group. However, there is no difference in both cytokine levels between TENSs of different frequencies in the spinal cord and DRG. We concluded that the M-TENS produced faster and better mechanical analgesia than the L-TENS in the mice skin/muscle incision retraction model. Those behavior differences were not in accordance with cytokine changes in the spinal cord or DRG.

Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice.

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Yang, Miyoung; Kim, Hwanseong; Kim, Juhwan; Kim, Sung-Ho; Kim, Jong-Choon; Bae, Chun-Sik; Kim, Joong-Sun; Shin, Taekyun; Moon, Changjong

2012-03-01

Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.

The therapeutic effect on bone mineral formation from biomimetic zinc containing tricalcium phosphate (ZnTCP in zinc-deficient osteoporotic mice.

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Joshua Chou

Full Text Available The aim of this study was to evaluate the therapeutic efficacy of biomimetic zinc-containing tricalcium phosphate (ZnTCP produced by hydrothermally converting calcium carbonate exoskeletons from foraminifera, in the treatment of osteoporotic mice. X-Ray powder diffraction showed crystallographic structures matching JCPDS profile for tricalcium phosphate. Mass spectroscopy used to calculate total composition amount showed similar amount of calcium (5×10(4 µg/g and phosphate (4×10(4 ppm after conversion and the presence of zinc (5.18×10(3 µg/g. In vitro zinc release showed no release in PBS buffer and <1% zinc release in 7 days. In vivo evaluation was done in ovariectomized mice by implanting the ZnTCP samples in the soft tissues near the right femur bone for four weeks. Thirty ddY mice (5 weeks old, average weight of 21 g were divided into six experimental groups (normal, sham, OVX, β-TCP, ZnTCP and direct injection of zinc. CT images were taken every two weeks where the bone mineral density (BMD and bone mineral content (BMC were calculated by software based on CT images. The ZnTCP group exhibits cortical and cancellous bone growth of 45% and 20% respectively. While sham, OVX and β-TCP suffered from bone loss. A correlation was made between the significant body weight increase in ZnTCP with the significant increase in plasma zinc level compared with OVX. The presented results indicate that biomimetic ZnTCP were effective in preventing and treating bone loss in osteoporotic mice model.

Attenuated Escherichia coli strains expressing the colonization factor antigen I (CFA/I) and a detoxified heat-labile enterotoxin (LThK63) enhance clearance of ETEC from the lungs of mice and protect mice from intestinal ETEC colonization and LT-induced fluid accumulation.

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Byrd, Wyatt; Boedeker, Edgar C

2013-03-15

Although enterotoxigenic Escherichia coli (ETEC) infections are important causes of infantile and traveler's diarrhea there is no licensed vaccine available for those at-risk. Our goal is to develop a safe, live attenuated ETEC vaccine. We used an attenuated E. coli strain (O157:H7, Δ-intimin, Stx1-neg, Stx2-neg) as a vector (ZCR533) to prepare two vaccine strains, one strain expressing colonization factor antigen I (ZCR533-CFA/I) and one strain expressing CFA/I and a detoxified heat-labile enterotoxin (ZCR533-CFA/I+LThK63) to deliver ETEC antigens to mucosal sites in BALB/c mice. Following intranasal and intragastric immunization with the vaccine strains, serum IgG and IgA antibodies were measured to the CFA/I antigen, however, only serum IgG antibodies were detected to the heat-labile enterotoxin. Intranasal administration of the vaccine strains induced respiratory and intestinal antibody responses to the CFA/I and LT antigens, while intragastric administration induced only intestinal antibody responses with no respiratory antibodies detected to the CFA/I and LT antigens. Mice immunized intranasally with the vaccine strains showed enhanced clearance of wild-type (wt) ETEC bacteria from the lungs. Mice immunized intranasally and intragastrically with the vaccine strains were protected from intestinal colonization following oral challenge with ETEC wt bacteria. Mice immunized intragastrically with the ZCR533-CFA/I+LThK63 vaccine strain had less fluid accumulate in their intestine following challenge with ETEC wt bacteria or with purified LT as compared to the sham mice indicating that the immunized mice were protected from LT-induced intestinal fluid accumulation. Thus, mice intragastrically immunized with the ZCR533-CFA/I+LThK63 vaccine strain were able to effectively neutralize the activity of the LT enterotoxin. However, no difference in intestinal fluid accumulation was detected in the mice immunized intranasally with the vaccine strain as compared to the sham

Accelerated intermittent Theta Burst stimulation for suicide risk in therapy-resistant depressed patients: a randomized, sham-controlled trial.

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Stefanie Desmyter

2016-09-01

Full Text Available Objectives We aimed to examine the effects and safety of accelerated intermittent Theta Burst Stimulation (iTBS on suicide risk in a group of treatment-resistant unipolar depressed patients, using an extensive suicide assessment scale. Methods In 50 therapy-resistant, antidepressant-free depressed patients, an intensive protocol of accelerated iTBS was applied over the left dorsolateral prefrontal cortex in a randomized, sham-controlled cross-over design. Patients received 20 iTBS sessions over 4 days. Suicide risk was assessed using the Beck Scale of Suicide ideation (BSI. Results The iTBS protocol was safe and well-tolerated. We observed a significant decrease of the BSI score over time, unrelated to active or sham stimulation and unrelated to depression-response. No worsening of suicidal ideation was observed. The effects of accelerated iTBS on mood and depression severity are reported in Duprat et al. (2016. The decrease in suicide risk lasted up to one month after baseline, even in depression non-responders. Conclusions This accelerated iTBS protocol was safe. The observed significant decrease in suicide risk was unrelated to active or sham stimulation and unrelated to depression response. Further sham-controlled research in suicidal depressed patients is necessary.(clinicaltrials.gov identifier: NCT01832805

Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial.

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Desmyter, Stefanie; Duprat, Romain; Baeken, Chris; Van Autreve, Sara; Audenaert, Kurt; van Heeringen, Kees

2016-01-01

Objectives: We aimed to examine the effects and safety of accelerated intermittent Theta Burst Stimulation (iTBS) on suicide risk in a group of treatment-resistant unipolar depressed patients, using an extensive suicide assessment scale. Methods: In 50 therapy-resistant, antidepressant-free depressed patients, an intensive protocol of accelerated iTBS was applied over the left dorsolateral prefrontal cortex (DLPFC) in a randomized, sham-controlled crossover design. Patients received 20 iTBS sessions over 4 days. Suicide risk was assessed using the Beck Scale of Suicide ideation (BSI). Results: The iTBS protocol was safe and well tolerated. We observed a significant decrease of the BSI score over time, unrelated to active or sham stimulation and unrelated to depression-response. No worsening of suicidal ideation was observed. The effects of accelerated iTBS on mood and depression severity are reported in Duprat et al. (2016). The decrease in suicide risk lasted up to 1 month after baseline, even in depression non-responders. Conclusions: This accelerated iTBS protocol was safe. The observed significant decrease in suicide risk was unrelated to active or sham stimulation and unrelated to depression response. Further sham-controlled research in suicidal depressed patients is necessary. (Clinicaltrials.gov identifier: NCT01832805).

Effects of Berberine Against Radiation-Induced Intestinal Injury in Mice

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Li Guanghui; Zhang Yaping; Tang Jinliang; Chen Zhengtang; Hu Yide; Wei Hong; Li Dezhi; Hao Ping; Wang Donglin

2010-01-01

Purpose: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. Methods and Materials: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-α, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT. The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. Results: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-α, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonalhehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). Conclusion: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.

The Effect of Sham Feeding on Neurocardiac Regulation in Healthy Human Volunteers

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Markad V Kamath

2007-01-01

Full Text Available BACKGROUND: Distension and electrical stimuli in the esophagus alter heart rate variability (HRV consistent with activation of vagal afferent and efferent pathways. Sham feeding stimulates gastric acid secretion by means of vagal efferent pathways. It is not known, however, whether activation of vagal efferent pathways is organ- or stimulus-specific.

Hydronephrosis alters cardiac ACE2 and Mas receptor expression in mice.

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Zhang, Yanling; Ma, Lulu; Wu, Junyan; Chen, Tingting

2015-06-01

Hydronephrosis is characterized by substantial loss of tubules and affects renin secretion in the kidney. However, whether alterations of angiotensin-converting enzyme (ACE), ACE2 and Mas receptor in the heart are observed in hydronephrosis is unknown. Thus, we assessed these components in hydronephrotic mice treated with AT1 receptor blockade and ACE inhibitor. Hydronephrosis was induced by left ureteral ligation in Balb/C mice except sham-operated animals. The levels of cardiac ACE, ACE2 and Mas receptor were measured after treatment of losartan or enalapril. Hydronephrosis led to an increase of ACE level and a decrease of ACE2 and Mas receptor in the heart. Losartan decreased cardiac ACE level, but ACE2 and Mas receptor levels significantly increased in hydronephrotic mice (p Hydronephrosis increased cardiac ACE and suppressed ACE2 and Mas receptor levels. AT1 blockade caused sustained activation of cardiac ACE2 and Mas receptor, but ACE inhibitor had the limitation of such activation of Mas receptor in hydronephrotic animals. © The Author(s) 2015.

Stimulatory effect of low dose radiation on the immune function in tumor-bearing mice

International Nuclear Information System (INIS)

Zhang Ying; Li Xiujuan; Li Xiuyi; Liu Shuzheng

1999-01-01

Objective: The author aims at investigating the effect of whole body irradiation (WBI) with low dose radiation on immune function in tumor-bearing mice. Methods: C57BL/6J mine implanted with Lewis lung carcinoma cells in the right thighs were used as an experimental animal model. WBI with 75 mGy X-rays was given at the 10 th day after implantation and immunological parameters were detected 18 hours after irradiation. The immunological parameters included the spontaneous incorporation of 3 H-TdR into thymocytes, the number of splenocytes, the reaction of splenocytes to ConA and LPS, the splenic production of IL-2, the cytotoxic activities of natural killer (NK) and lymphokine activated killer cells (LAK) as well as specific cytotoxic T lymphocytes (CTL). Results: The immunological parameters of irradiated tumor-bearing mice were significantly increased compared with those of sham-irradiated tumor-bearing mice (P<0.05∼0.01). Conclusion: Low dose radiation could significantly increase the immune function of tumor-bearing mice, and this stimulatory effect may be of some potential significance in tumor therapy

On extending Kohn-Sham density functionals to systems with fractional number of electrons.

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Li, Chen; Lu, Jianfeng; Yang, Weitao

2017-06-07

We analyze four ways of formulating the Kohn-Sham (KS) density functionals with a fractional number of electrons, through extending the constrained search space from the Kohn-Sham and the generalized Kohn-Sham (GKS) non-interacting v-representable density domain for integer systems to four different sets of densities for fractional systems. In particular, these density sets are (I) ensemble interacting N-representable densities, (II) ensemble non-interacting N-representable densities, (III) non-interacting densities by the Janak construction, and (IV) non-interacting densities whose composing orbitals satisfy the Aufbau occupation principle. By proving the equivalence of the underlying first order reduced density matrices associated with these densities, we show that sets (I), (II), and (III) are equivalent, and all reduce to the Janak construction. Moreover, for functionals with the ensemble v-representable assumption at the minimizer, (III) reduces to (IV) and thus justifies the previous use of the Aufbau protocol within the (G)KS framework in the study of the ground state of fractional electron systems, as defined in the grand canonical ensemble at zero temperature. By further analyzing the Aufbau solution for different density functional approximations (DFAs) in the (G)KS scheme, we rigorously prove that there can be one and only one fractional occupation for the Hartree Fock functional, while there can be multiple fractional occupations for general DFAs in the presence of degeneracy. This has been confirmed by numerical calculations using the local density approximation as a representative of general DFAs. This work thus clarifies important issues on density functional theory calculations for fractional electron systems.

Effective electronic-only Kohn–Sham equations for the muonic molecules

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Rayka, Milad; Goli, Mohammad; Shahbazian, Shant

A set of effective electronic-only Kohn-Sham (EKS) equations are derived for the muonic molecules (containing a positively charged muon), which are completely equivalent to the coupled electronic-muonic Kohn-Sham equations derived previously within the framework of the Nuclear-Electronic Orbital density functional theory (NEO-DFT). The EKS equations contain effective non-coulombic external potentials depending on parameters describing muon vibration, which are optimized during the solution of the EKS equations making muon KS orbital reproducible. It is demonstrated that the EKS equations are derivable from a certain class of effective electronic Hamiltonians through applying the usual Hohenberg-Kohn theorems revealing a duality between the NEO-DFT and the effective electronic-only DFT methodologies. The EKS equations are computationally applied to a small set of muoniated organic radicals and it is demonstrated that a mean effective potential maybe derived for this class of muonic species while an electronic basis set is also designed for the muon. These computational ingredients are then applied to muoniated ferrocenyl radicals, which had been previously detected experimentally through adding muonium atom to ferrocene. In line with previous computational studies, from the six possible species the staggered conformer, where the muon is attached to the exo position of the cyclopentadienyl ring, is deduced to be the most stable ferrocenyl radical.

Effective electronic-only Kohn-Sham equations for the muonic molecules.

Science.gov (United States)

Rayka, Milad; Goli, Mohammad; Shahbazian, Shant

2018-03-28

A set of effective electronic-only Kohn-Sham (EKS) equations are derived for the muonic molecules (containing a positively charged muon), which are completely equivalent to the coupled electronic-muonic Kohn-Sham equations derived previously within the framework of the nuclear-electronic orbital density functional theory (NEO-DFT). The EKS equations contain effective non-coulombic external potentials depending on parameters describing the muon's vibration, which are optimized during the solution of the EKS equations making the muon's KS orbital reproducible. It is demonstrated that the EKS equations are derivable from a certain class of effective electronic Hamiltonians through applying the usual Hohenberg-Kohn theorems revealing a "duality" between the NEO-DFT and the effective electronic-only DFT methodologies. The EKS equations are computationally applied to a small set of muoniated organic radicals and it is demonstrated that a mean effective potential may be derived for this class of muonic species while an electronic basis set is also designed for the muon. These computational ingredients are then applied to muoniated ferrocenyl radicals, which had been previously detected experimentally through adding a muonium atom to ferrocene. In line with previous computational studies, from the six possible species, the staggered conformer, where the muon is attached to the exo position of the cyclopentadienyl ring, is deduced to be the most stable ferrocenyl radical.

Do mobile phone base stations affect sleep of residents? Results from an experimental double-blind sham-controlled field study.

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Danker-Hopfe, Heidi; Dorn, Hans; Bornkessel, Christian; Sauter, Cornelia

2010-01-01

The aim of the present double-blind, sham-controlled, balanced randomized cross-over study was to disentangle effects of electromagnetic fields (EMF) and non-EMF effects of mobile phone base stations on objective and subjective sleep quality. In total 397 residents aged 18-81 years (50.9% female) from 10 German sites, where no mobile phone service was available, were exposed to sham and GSM (Global System for Mobile Communications, 900 MHz and 1,800 MHz) base station signals by an experimental base station while their sleep was monitored at their homes during 12 nights. Participants were randomly exposed to real (GSM) or sham exposure for five nights each. Individual measurement of EMF exposure, questionnaires on sleep disorders, overall sleep quality, attitude towards mobile communication, and on subjective sleep quality (morning and evening protocols) as well as objective sleep data (frontal EEG and EOG recordings) were gathered. Analysis of the subjective and objective sleep data did not reveal any significant differences between the real and sham condition. During sham exposure nights, objective and subjective sleep efficiency, wake after sleep onset, and subjective sleep latency were significantly worse in participants with concerns about possible health risks resulting from base stations than in participants who were not concerned. The study did not provide any evidence for short-term physiological effects of EMF emitted by mobile phone base stations on objective and subjective sleep quality. However, the results indicate that mobile phone base stations as such (not the electromagnetic fields) may have a significant negative impact on sleep quality. (c) 2010 Wiley-Liss, Inc.

A quadratic form of the Coulomb operator and an optimization scheme for the extended Kohn-Sham models

International Nuclear Information System (INIS)

Kusakabe, Koichi

2009-01-01

To construct an optimization scheme for an extension of the Kohn-Sham approach, I introduce an operator form of the Coulomb interaction. This form is the sum of quadratic form pairs, which can be redefined in a self-consistent calculation of a multi-reference density functional theory. A detailed derivation of the form is given. A fluctuation term introduced in the extended Kohn-Sham scheme is expressed in this form for regularization. The present procedure also provides an exact derivation of effective negative interactions in charge fluctuation channels. Relevance to high-temperature superconductors is discussed.

Vagotomy attenuates brain cytokines and sleep induced by peripherally administered tumor necrosis factor-α and lipopolysaccharide in mice.

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Zielinski, Mark R; Dunbrasky, Danielle L; Taishi, Ping; Souza, Gianne; Krueger, James M

2013-08-01

Systemic tumor necrosis factor-α (TNF-α) is linked to sleep and sleep altering pathologies in humans. Evidence from animals indicates that systemic and brain TNF-α have a role in regulating sleep. In animals, TNF-α or lipopolysaccharide (LPS) enhance brain pro-inflammatory cytokine expression and sleep after central or peripheral administration. Vagotomy blocks enhanced sleep induced by systemic TNF-α and LPS in rats, suggesting that vagal afferent stimulation by TNF-α enhances pro-inflammatory cytokines in sleep-related brain areas. However, the effects of systemic TNF-α on brain cytokine expression and mouse sleep remain unknown. We investigated the role of vagal afferents on brain cytokines and sleep after systemically applied TNF-α or LPS in mice. Spontaneous sleep was similar in vagotomized and sham-operated controls. Vagotomy attenuated TNF-α- and LPS-enhanced non-rapid eye movement sleep (NREMS); these effects were more evident after lower doses of these substances. Vagotomy did not affect rapid eye movement sleep responses to these substances. NREMS electroencephalogram delta power (0.5-4 Hz range) was suppressed after peripheral TNF-α or LPS injections, although vagotomy did not affect these responses. Compared to sham-operated controls, vagotomy did not affect liver cytokines. However, vagotomy attenuated interleukin-1 beta (IL-1β) and TNF-α mRNA brain levels after TNF-α, but not after LPS, compared to the sham-operated controls. We conclude that vagal afferents mediate peripheral TNF-α-induced brain TNF-α and IL-1β mRNA expressions to affect sleep. We also conclude that vagal afferents alter sleep induced by peripheral pro-inflammatory stimuli in mice similar to those occurring in other species.

Enhanced susceptibility to stress and seizures in GAD65 deficient mice.

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Qi, Jin; Kim, Minjung; Sanchez, Russell; Ziaee, Saba M; Kohtz, Jhumku D; Koh, Sookyong

2018-01-01

Reduced gamma-aminobutyric acid (GABA) inhibition has been implicated in both anxiety and epilepsy. GAD65-/- (NOD/LtJ) mice have significantly decreased basal GABA levels in the brain and a lowered threshold for seizure generation. One fifth of GAD65 -/- mice experienced stress-induced seizures upon exposure to an open field at 4 weeks of age. In each successive week until 8 weeks of age, the latency to seizures decreased with prior seizure experience. 100% of GAD65-/- mice exhibited stress-induced seizures by the end of 8 weeks. GAD65-/- mice also exhibited marked impairment in open field exploratory behavior and deficits in spatial learning acquisition on a Barnes maze. Anxiety-like behavior in an open field was observed prior to seizure onset and was predictive of subsequent seizures. Immunohistochemical characterization of interneuron subtypes in GAD65-/- mice showed a selective decrease in GABA and neuropeptide Y (NPY) levels and no change in calbindin (CLB) or calretinin (CLR) immunoreactivity in the hippocampus. Stem cells from the medial ganglionic eminence (MGE) were injected into the hippocampal hilus to restore GABAergic interneurons. One week after transplantation, MGE-transplanted mice demonstrated significant seizure resistance compared to sham surgical controls. The percent area of GFP+ MGE graft in the hippocampus correlated significantly with the increase in seizure latency. Our data indicate that impaired GABAergic neurotransmission can cause anxiety-like behavior and stress-induced seizures that can be rescued by MGE stem cell transplantation.

Adenosine A2A Receptors Mediate Anti-Inflammatory Effects of Electroacupuncture on Synovitis in Mice with Collagen-Induced Arthritis

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Qi-hui Li

2015-01-01

Full Text Available To study the role of adenosine A2A receptor (A2AR in mediating the anti-inflammatory effect of electroacupuncture (EA on synovitis in collagen-induced arthritis (CIA, C57BL/6 mice were divided into five treatment groups: Sham-control, CIA-control, CIA-EA, CIA-SCH58261 (A2AR antagonist, and CIA-EA-SCH58261. All mice except those in the Sham-control group were immunized with collagen II for arthritis induction. EA treatment was administered using the stomach 36 and spleen 6 points, and stimulated with a continuous rectangular wave for 30 min daily. EA treatment and SCH58261 were administered daily from days 35 to 49 (n=10. After treatment, X-ray radiography of joint bone morphology was established at day 60 and mouse blood was collected for ELISA determination of tumor necrosis factor alpha (TNF-α levels. Mice were sacrificed and processed for histological examination of pathological changes of joint tissue, including hematoxylin-eosin staining and immunohistochemistry of A2AR expression. EA treatment resulted in significantly reduced pathological scores, TNF-α concentrations, and bone damage X-ray scores. Importantly, the anti-inflammatory and tissue-protective effect of EA treatment was reversed by coadministration of SCH58261. Thus, EA treatment exerts an anti-inflammatory effect resulting in significant protection of cartilage by activation of A2AR in the synovial tissue of CIA.

Evaluating the importance of sham controlled trials in the investigation of medical devices in interventional cardiology.

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Byrne, Robert A; Capodanno, Davide; Mahfoud, Felix; Fajadet, Jean; Windecker, Stephan; Jüni, Peter; Baumbach, Andreas; Wijns, William; Haude, Michael

2018-05-22

Cardiovascular medicine is one of the specialties that has relied most heavily on evidence from randomized clinical trials in determining best practice for the management of common disease conditions. When comparing treatment approaches, trials incorporating random allocation are the most appropriate method for protecting against treatment allocation bias. In order to protect against performance and ascertainment bias, trial designs including placebo control are preferable where feasible. In contrast to testing of medicines, treatments based on procedures or use of medical devices are more challenging to assess, as sham procedures are necessary to facilitate blinding of participants. However, in many cases, ethical concerns exist, as individual patients allocated to sham procedure are exposed only to risk without potential for benefit. Accordingly, the potential benefits to the general patient population must be carefully weighed against the risks of the exposed individuals. For this reason, trial design and study conduct are critically important to ensure that the investigation has the best chance of answering the study question at hand. In the current manuscript, we aim to review issues relating to the conduct of sham-controlled trials and discuss a number of recent examples in the field of interventional cardiology.

Sodium pertechnetate (Na99mTcO4) biodistribution in mice exposed to cigarette smoke

International Nuclear Information System (INIS)

Valenca, Samuel S; Lima, Elaine AC; Dire, Gláucio F; Bernardo-Filho, Mário; Porto, Luís Cristóvão

2005-01-01

The biological effects of cigarette smoke are not fully known. To improve our understanding of the action of various chemical agents, we investigated the biodistribution of sodium pertechnetate (Na 99m TcO 4 ) in mice exposed to cigarette smoke. Fifteen BALB/c male mice were exposed to the smoke of nine whole commercial cigarettes per day, 3 times/day, for up to 10 days to whole body exposure in a chamber. A control group of 5 BALB/c male mice was sham-smoked. One day later, the exposed and control groups of mice received (7.4 MBq/0.3 ml) of Na 99m TcO 4 before being killed at 30 min. Bones, brain, heart, intestine, kidney, liver, lungs, muscle, pancreas, spleen, stomach, testis and thyroid were weighed and these organs and blood radioactivity recorded with a gamma counter. The percentage per gram of tissue of injected dose (%ID/g) was determined for each organ. Cigarette smoke significantly decreased (p < 0.05) the %ID/g in red blood cells, bone, kidney, lung, spleen, stomach, testis and thyroid of the exposed mice. The toxic effects of cigarette smoke reduced the Na 99m TcO 4 biodistribution

A self-made, low-cost infrared system for evaluating the sciatic functional index in mice

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Lukas Fricker

2016-01-01

Full Text Available The sciatic functional index (SFI is a popular parameter for peripheral nerve evaluation that relies on footprints obtained with ink and paper. Drawbacks include smearing artefacts and a lack of dynamic information during measurement. Modern applications use digitized systems that can deliver results with less analytical effort and fewer mice. However, the systems are expensive (€40,000. This study aimed to evaluate the applicability and precision of a self-made, low-cost infrared system for evaluating SFI in mice. Mice were subjected to unilateral sciatic nerve crush injury (crush group; n = 7 and sham operation (sham group; n = 4. They were evaluated on the day before surgery, the 2 nd , 4 th and 6 th days after injury, and then every day up to the 23 rd day after injury. We compared two SFI evaluation methods, i.e., conventional ink-and-paper SFI (C-SFI and our infrared system (I-SFI. Our apparatus visualized footprints with totally internally reflected infrared light (950 nm and a camera that can only detect this wavelength. Additionally we performed an analysis with the ladder beam walking test (LBWT as a reference test. I-SFI assessment reduced the standard deviation by about 33 percent, from 11.6 to 7.8, and cut the variance around the baseline to 21 percent. The system thus requires fewer measurement repetitions and fewer animals, and cuts the cost of keeping the animals. The apparatus cost €321 to build. Our results show that the process of obtaining the SFI can be made more precise via digitization with a self-made, low-cost infrared system.

A self-made, low-cost infrared system for evaluating the sciatic functional index in mice.

Science.gov (United States)

Fricker, Lukas; Penna, Vincenzo; Lampert, Florian; Stark, G Bjoern; Witzel, Christian; Koulaxouzidis, Georgios

2016-05-01

The sciatic functional index (SFI) is a popular parameter for peripheral nerve evaluation that relies on footprints obtained with ink and paper. Drawbacks include smearing artefacts and a lack of dynamic information during measurement. Modern applications use digitized systems that can deliver results with less analytical effort and fewer mice. However, the systems are expensive (€40,000). This study aimed to evaluate the applicability and precision of a self-made, low-cost infrared system for evaluating SFI in mice. Mice were subjected to unilateral sciatic nerve crush injury (crush group; n = 7) and sham operation (sham group; n = 4). They were evaluated on the day before surgery, the 2(nd), 4(th) and 6(th) days after injury, and then every day up to the 23(rd) day after injury. We compared two SFI evaluation methods, i.e., conventional ink-and-paper SFI (C-SFI) and our infrared system (I-SFI). Our apparatus visualized footprints with totally internally reflected infrared light (950 nm) and a camera that can only detect this wavelength. Additionally we performed an analysis with the ladder beam walking test (LBWT) as a reference test. I-SFI assessment reduced the standard deviation by about 33 percent, from 11.6 to 7.8, and cut the variance around the baseline to 21 percent. The system thus requires fewer measurement repetitions and fewer animals, and cuts the cost of keeping the animals. The apparatus cost €321 to build. Our results show that the process of obtaining the SFI can be made more precise via digitization with a self-made, low-cost infrared system.

The effects of acupuncture versus sham acupuncture in the treatment of fibromyalgia: a randomized controlled clinical trial

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Fatma Gülçin Uğurlu

2017-01-01

Full Text Available Abstract OBJECTIVE: The aim of this manuscript is to determine and to compare the efficacy of real acupuncture with sham acupuncture on fibromyalgia (FM treatment. METHODS: 50 women with FM were randomized into 2 groups to receive either true acupuncture or sham acupuncture. Subjects were evaluated with VAS (at night, at rest, during activity, SF-36, Fibromyalgia Impact Questionnaire (FIQ, Beck Depression scale (BDI, Fatigue Severity Scale (FSS at baseline, 1 month and 2 months after the 1st session. Patients in both groups received 3 sessions in the 1st week, 2 sessions/week during 2 weeks and 1 session/week in the following 5 weeks (totally 12 sessions. RESULTS: 25 subjects with a mean age of 47,28±7,86 years were enrolled in true acupuncture group and 25 subjects with a mean age of 43,60±8,18 years were enrolled in sham acupuncture group. Both groups improved significantly in all parameters 1 month after the 1st session and this improvement persisted 2 months after the 1st session (p

Effect of Porphyromonas gingivalis infection on post-transcriptional regulation of the low-density lipoprotein receptor in mice

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Miyazawa Haruna

2012-09-01

Full Text Available Abstract Background Periodontal disease is suggested to increase the risk of atherothrombotic disease by inducing dyslipidemia. Recently, we demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9, which is known to play a critical role in the regulation of circulating low-density lipoprotein (LDL cholesterol levels, is elevated in periodontitis patients. However, the underlying mechanisms of elevation of PCSK9 in periodontitis patients are largely unknown. Here, we explored whether Porphyromonas gingivalis, a representative periodontopathic bacterium, -induced inflammatory response regulates serum PCSK9 and cholesterol levels using animal models. Methods We infected C57BL/6 mice intraperitoneally with Porphyromonas gingivalis, a representative strain of periodontopathic bacteria, and evaluated serum PCSK9 levels and the serum lipid profile. PCSK9 and LDL receptor (LDLR gene and protein expression, as well as liver X receptors (Lxrs, inducible degrader of the LDLR (Idol, and sterol regulatory element binding transcription factor (Srebf2 gene expression, were examined in the liver. Results P. gingivalis infection induced a significant elevation of serum PCSK9 levels and a concomitant elevation of total and LDL cholesterol compared with sham-infected mice. The LDL cholesterol levels were significantly correlated with PCSK9 levels. Expression of the Pcsk9, Ldlr, and Srebf2 genes was upregulated in the livers of the P. gingivalis-infected mice compared with the sham-infected mice. Although Pcsk9 gene expression is known to be positively regulated by sterol regulatory element binding protein (SREBP2 (human homologue of Srebf2, whereas Srebf2 is negatively regulated by cholesterol, the elevated expression of Srebf2 found in the infected mice is thought to be mediated by P. gingivalis infection. Conclusions P. gingivalis infection upregulates PCSK9 production via upregulation of Srebf2, independent of cholesterol levels. Further studies

UTP reduces infarct size and improves mice heart function after myocardial infarct via P2Y2 receptor

DEFF Research Database (Denmark)

Cohen, A; Shainberg, Asher; Hochhauser, E

2011-01-01

Pyrimidine nucleotides are signaling molecules, which activate G protein-coupled membrane receptors of the P2Y family. P2Y(2) and P2Y(4) receptors are part of the P2Y family, which is composed of 8 subtypes that have been cloned and functionally defined. We have previously found that uridine-5......'-triphosphate (UTP) reduces infarct size and improves cardiac function following myocardial infarct (MI). The aim of the present study was to determine the role of P2Y(2) receptor in cardiac protection following MI using knockout (KO) mice, in vivo and wild type (WT) for controls. In both experimental groups...... used (WT and P2Y(2)(-/-) receptor KO mice) there were 3 subgroups: sham, MI, and MI+UTP. 24h post MI we performed echocardiography and measured infarct size using triphenyl tetrazolium chloride (TTC) staining on all mice. Fractional shortening (FS) was higher in WT UTP-treated mice than the MI group...

Iron dysregulation combined with aging prevents sepsis-induced apoptosis.

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Javadi, Pardis; Buchman, Timothy G; Stromberg, Paul E; Turnbull, Isaiah R; Vyas, Dinesh; Hotchkiss, Richard S; Karl, Irene E; Coopersmith, Craig M

2005-09-01

Sepsis, iron loading, and aging cause independent increases in gut epithelial and splenic apoptosis. It is unknown how their combination will affect apoptosis and systemic cytokine levels. Hfe-/- mice (a murine homologue of hemochromatosis) abnormally accumulate iron in their tissues. Aged (24-26 months) or mature (16-18 months) Hfe-/- mice and wild type (WT) littermates were subjected to cecal ligation and puncture (CLP) or sham laparotomy. Intestine, spleen, and blood were harvested 24 h later and assessed for apoptosis and cytokine levels. Gut epithelial and splenic apoptosis were low in both aged septic and sham Hfe-/- mice, regardless of the amount of iron in their diet. Mature septic WT mice had increased apoptosis compared to age-matched sham WT mice. Mature septic Hfe-/- mice had similar levels of intestinal cell death to age-matched septic WT mice but higher levels of splenic apoptosis. Apoptosis was significantly lower in septic aged Hfe-/- mice than septic mature Hfe-/- animals. Interleukin-6 was elevated in septic aged Hfe-/- mice compared to sham mice. Although sepsis, chronic iron dysregulation, and aging each increase gut and splenic apoptosis, their combination yields cell death levels similar to sham animals despite the fact that aged Hfe-/- mice are able to mount an inflammatory response following CLP and mature Hfe-/- mice have elevated sepsis-induced apoptosis. Combining sepsis with two risk factors that ordinarily increase cell death and increase mortality in CLP yields an apoptotic response that could not have been predicted based upon each element in isolation.

Circular swimming in mice after exposure to a high magnetic field.

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Houpt, Thomas A; Houpt, Charles E

2010-06-16

There is increasing evidence that exposure to high magnetic fields of 4T and above perturbs the vestibular system of rodents and humans. Performance in a swim test is a sensitive test of vestibular function. In order to determine the effect of magnet field exposure on swimming in mice, mice were exposed for 30 min within a 14.1T superconducting magnet and then tested at different times after exposure in a 2-min swim test. As previously observed in open field tests, mice swam in tight counter-clockwise circles when tested immediately after magnet exposure. The counter-clockwise orientation persisted throughout the 2-min swim test. The tendency to circle was transient, because no significant circling was observed when mice were tested at 3 min or later after magnet exposure. However, mice did show a decrease in total distance swum when tested between 3 and 40 min after magnet exposure. The decrease in swimming distance was accompanied by a pronounced postural change involving a counter-clockwise twist of the pelvis and hindlimbs that was particularly severe in the first 15s of the swim test. Finally, no persistent difference from sham-exposed mice was seen in the swimming of magnet-exposed mice when tested 60 min, 24h, or 96 h after magnet exposure. This suggests that there is no long-lasting effect of magnet exposure on the ability of mice to orient or swim. The transient deficits in swimming and posture seen shortly after magnet exposure are consistent with an acute perturbation of the vestibular system by the high magnetic field. (c) 2010 Elsevier Inc. All rights reserved.

Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by photobiomodulation induced by 670 nm light.

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Kamaldeen A Muili

Full Text Available The approved immunomodulatory agents for the treatment of multiple sclerosis (MS are only partially effective. It is thought that the combination of immunomodulatory and neuroprotective strategies is necessary to prevent or reverse disease progression. Irradiation with far red/near infrared light, termed photobiomodulation, is a therapeutic approach for inflammatory and neurodegenerative diseases. Data suggests that near-infrared light functions through neuroprotective and anti-inflammatory mechanisms. We sought to investigate the clinical effect of photobiomodulation in the Experimental Autoimmune Encephalomyelitis (EAE model of multiple sclerosis.The clinical effect of photobiomodulation induced by 670 nm light was investigated in the C57BL/6 mouse model of EAE. Disease was induced with myelin oligodendrocyte glycoprotein (MOG according to standard laboratory protocol. Mice received 670 nm light or no light treatment (sham administered as suppression and treatment protocols. 670 nm light reduced disease severity with both protocols compared to sham treated mice. Disease amelioration was associated with down-regulation of proinflammatory cytokines (interferon-γ, tumor necrosis factor-α and up-regulation of anti-inflammatory cytokines (IL-4, IL-10 in vitro and in vivo.These studies document the therapeutic potential of photobiomodulation with 670 nm light in the EAE model, in part through modulation of the immune response.

Effects of gasoline engine emissions on preexisting allergic airway responses in mice.

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Day, Kimberly C; Reed, Matthew D; McDonald, Jacob D; Seilkop, Steven K; Barrett, Edward G

2008-10-01

Gasoline-powered vehicle emissions contribute significantly to ambient air pollution. We hypothesized that exposure to gasoline engine emissions (GEE) may exacerbate preexisting allergic airway responses. Male BALB/c mice were sensitized by injection with ovalbumin (OVA) and then received a 10-min aerosolized OVA challenge. Parallel groups were sham-sensitized with saline. Mice were exposed 6 h/day to air (control, C) or GEE containing particulate matter (PM) at low (L), medium (M), or high (H) concentrations, or to the H level with PM removed by filtration (high-filtered, HF). Immediately after GEE exposure mice received another 10-min aerosol OVA challenge (pre-OVA protocol). In a second (post-OVA) protocol, mice were similarly sensitized but only challenged to OVA before air or GEE exposure. Measurements of airway hyperresponsiveness (AHR), bronchoalveolar lavage (BAL), and blood collection were performed approximately 24 h after the last exposure. In both protocols, M, H, and HF GEE exposure significantly decreased BAL neutrophils from nonsensitized mice but had no significant effect on BAL cells from OVA-sensitized mice. In the pre-OVA protocol, GEE exposure increased OVA-specific IgG(1) but had no effect on BAL interleukin (IL)-2, IL-4, IL-13, or interferon (IFN)-gamma in OVA-sensitized mice. Nonsensitized GEE-exposed mice had increased OVA-specific IgG(2a), IgE, and IL-2, but decreased total IgE. In the post-OVA protocol, GEE exposure reduced BAL IL-4, IL-5, and IFN-gamma in nonsensitized mice but had no effect on sensitized mice. These results suggest acute exposure to the gas-vapor phase of GEE suppressed inflammatory cells and cytokines from nonsensitized mice but did not substantially exacerbate allergic responses.

Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy.

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Mercuri, Eugenio; Darras, Basil T; Chiriboga, Claudia A; Day, John W; Campbell, Craig; Connolly, Anne M; Iannaccone, Susan T; Kirschner, Janbernd; Kuntz, Nancy L; Saito, Kayoko; Shieh, Perry B; Tulinius, Már; Mazzone, Elena S; Montes, Jacqueline; Bishop, Kathie M; Yang, Qingqing; Foster, Richard; Gheuens, Sarah; Bennett, C Frank; Farwell, Wildon; Schneider, Eugene; De Vivo, Darryl C; Finkel, Richard S

2018-02-15

Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills. In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; PCHERISH ClinicalTrials.gov number, NCT02292537 .).

Single Hind Limb Burn Injury to Mice Alters NF Kappa B (NF-κB) Expression and [18F] 2-Fluoro-2-Deoxy-d-Glucose (FDG) Uptake

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Carter, Edward A.; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A.; Jung, Walter; Tompkins, Ronald G.; Fischman, Alan J.

2014-01-01

Burn trauma to the extremities can produce marked systemic effects in mice1, 6, 7. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism (18FDG uptake) by brown adipose tissue (BAT) and NF-κB activity in a number of tissues including skeletal muscle. This study examined the effect of a single hindlimb burn in mice on 18FDG uptake by in vivo, NF-κB activity in vivo, and blood flow determined by laser Doppler techniques. Male mice NF-κB luciferase reporter mice (28 grams- 30 grams, male) were anesthetized, both legs were shaven, and the right leg was subjected to scald injury by immersion in 90°C water for 5 seconds. Sham treated animals were used as controls. Each burned and sham mouse was resuscitated with saline (2 ml, IP). The individual animals were placed in wire bottom cages with no food and free access to water. 24 hrs later, the animals were imaged with Laser Doppler for measurements of blood flow in the hind limb. The animals were then injected unanesthetized with 50 µCi of FDG or luciferin (1.0 mg), I.V. via tail vein. Five minutes after luciferin injection, NF-kB mice were studied by bioluminescence imaging with a CCD camera. One hour after 18FDG injection the animals were euthanized with carbon dioxide overdose and 18FDG biodistribution was measured. Tissues were also analyzed for NF-κB luciferase activity. The scalding procedure used here produced a full thickness burn injury to the leg with sharp margins. 18FDG uptake by the burned leg was lower than in the contralateral limb. Similarly luciferase activity and blood flow in the burned leg were lower than in the contralateral leg. 18FDG uptake by BAT and heart was increased, while brain was decreased. In conclusion, the present study suggests that burn injury to a single leg reduced 18FDG uptake by skeletal muscle but increased 18FDG uptake by BAT. The injury to the leg reduced NF-κB expression as compared to the contralateral leg and the uninjured

Sleep improvement for restless legs syndrome patients. Part IV: meta-analysis comparison of effect sizes of vibratory stimulation sham pads and placebo pills

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Burbank F

2014-02-01

Full Text Available Fred Burbank Salt Creek International Women's Health Foundation, San Clemente, CA, USA Purpose: To determine whether sham pads used as controls in randomized clinical trials of vibratory stimulation to treat patients with sleep loss associated with restless legs syndrome perform differently than placebo pills used in comparable restless legs syndrome drug trials. Patients and methods: Sham pad effect sizes from 66 control patients in two randomized clinical trials of vibratory stimulation were compared with placebo responses from 1,024 control patients in 12 randomized clinical drug trials reporting subjective sleep measurement scales. Control patient responses were measured as the standardized difference in means corrected for correlation between beginning and ending scores and for small sample sizes. Results: For parallel randomized clinical trials, sham effects in vibratory stimulation trials were not significantly different from placebo effects in drug trials (0.37 and 0.31, respectively, Qbetween subgroups =0.25, PQ≥0.62. Placebo effect sizes were significantly smaller in crossover drug trials than sham effect sizes in parallel vibratory stimulation trials (0.07 versus 0.37, respectively, Qbetween subgroups =4.59, PQ≤0.03 and placebo effect sizes in parallel drug trials (0.07 versus 0.31, respectively, Qbetween subgroups =5.50, PQ≤0.02. Conclusion: For subjective sleep loss assessments in parallel trials, sham pads in vibratory stimulation trials performed similarly to placebo pills in drug trials. Trial design (parallel versus crossover had a large influence on control effect sizes. Placebo pills in crossover drug trials had significantly smaller effect sizes than sham pads in parallel vibratory stimulation trials or placebo pills in parallel drug trials. Keywords: sham effect, placebo effect, trial design, crossover study, parallel study, counterstimulation

On the Efficiency of Algorithms for Solving Hartree–Fock and Kohn–Sham Response Equations

DEFF Research Database (Denmark)

Kauczor, Joanna; Jørgensen, Poul; Norman, Patrick

2011-01-01

The response equations as occurring in the Hartree–Fock, multiconfigurational self-consistent field, and Kohn–Sham density functional theory have identical matrix structures. The algorithms that are used for solving these equations are discussed, and new algorithms are proposed where trial vectors...

Electroacupuncture versus sham electroacupuncture for urinary retention in poststroke patients: study protocol for a multicenter, randomized controlled trial.

Science.gov (United States)

Shin, Seungwon; Lee, Jiwon; Yoo, Junghee; Lim, Sung Min; Lee, Euiju

2016-04-12

This study protocol evaluates the effectiveness of adjuvant electroacupuncture (EA) for urinary retention in poststroke patients undergoing conventional treatments, in comparison with that of a sham control. A multicenter, blinded, randomized controlled trial will be conducted in three hospitals in the Republic of Korea. We are recruiting 54 stroke survivors (aged >19 years), who were diagnosed with urinary retention based on the results of two consecutive post-void residual (PVR) tests, and dividing them randomly into two arms: the EA and Park-sham control groups. They will receive ten sessions of EA or sham treatment for 2 weeks. The participants will be blinded with non-penetrating needles and fake sounds of EA stimulators. The daily PVR ratio will be primarily measured at baseline and at the end of the study to statistically test the effectiveness of EA for poststroke urinary retention. Then, the Korean version of the Qualiveen Questionnaire, the Korean version of the International Prostate Symptom Score, and the blinding index will be assessed. After each EA session or sham EA, adverse events will be reported to evaluate the safety of EA. Results will be analyzed by using the independent t-test or Mann-Whitney U test, based on both intention-to-treat and per-protocol principles. The findings will provide clinical evidence for the effectiveness of EA treatment to improve urinary retention in stroke survivors. This study protocol was registered in ClinicalTrials.gov (NCT02472288) on 10 June 2015.

Changes in vision- and health-related quality of life in patients with diabetic macular edema treated with pegaptanib sodium or sham

DEFF Research Database (Denmark)

Loftus, Jane V; Sultan, Marla B; Pleil, Andreas M

2011-01-01

To compare vision function and self-reported quality of life (QoL) in patients with diabetic macular edema (DME) treated with intravitreous pegaptanib 0.3 mg or sham injection.......To compare vision function and self-reported quality of life (QoL) in patients with diabetic macular edema (DME) treated with intravitreous pegaptanib 0.3 mg or sham injection....

[Responsibility due to medication errors in France: a study based on SHAM insurance data].

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Theissen, A; Orban, J-C; Fuz, F; Guerin, J-P; Flavin, P; Albertini, S; Maricic, S; Saquet, D; Niccolai, P

2015-03-01

The safe medication practices at the hospital constitute a major public health problem. Drug supply chain is a complex process, potentially source of errors and damages for the patient. SHAM insurances are the biggest French provider of medical liability insurances and a relevant source of data on the health care complications. The main objective of the study was to analyze the type and cause of medication errors declared to SHAM and having led to a conviction by a court. We did a retrospective study on insurance claims provided by SHAM insurances with a medication error and leading to a condemnation over a 6-year period (between 2005 and 2010). Thirty-one cases were analysed, 21 for scheduled activity and 10 for emergency activity. Consequences of claims were mostly serious (12 deaths, 14 serious complications, 5 simple complications). The types of medication errors were a drug monitoring error (11 cases), an administration error (5 cases), an overdose (6 cases), an allergy (4 cases), a contraindication (3 cases) and an omission (2 cases). Intravenous route of administration was involved in 19 of 31 cases (61%). The causes identified by the court expert were an error related to service organization (11), an error related to medical practice (11) or nursing practice (13). Only one claim was due to the hospital pharmacy. The claim related to drug supply chain is infrequent but potentially serious. These data should help strengthen quality approach in risk management. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Effects of continuous positive airway pressure on energy intake in obstructive sleep apnea: A pilot sham-controlled study

OpenAIRE

Shechter, Ari; Kovtun, Kyle; St-Onge, Marie-Pierre

2016-01-01

Obesity is among the leading risk factors for obstructive sleep apnea (OSA). A reciprocal relationship between obesity and OSA has been proposed, which may be due to excessive food intake. We conducted a pilot study to test the effects of continuous positive airway pressure (CPAP) on energy intake (EI) in OSA patients using a sham-controlled crossover design. In-laboratory total daily EI was assessed after 2 mo of active and sham CPAP. Four men were enrolled (age ± SEM: 51.8 ± 2.1 y; body mas...

Evoked Pressure Pain Sensitivity Is Associated with Differential Analgesic Response to Verum and Sham Acupuncture in Fibromyalgia.

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Zucker, Noah A; Tsodikov, Alex; Mist, Scott D; Cina, Stephen; Napadow, Vitaly; Harris, Richard E

2017-08-01

Fibromyalgia is a chronic pain condition with few effective treatments. Many fibromyalgia patients seek acupuncture for analgesia; however, its efficacy is limited and not fully understood. This may be due to heterogeneous pathologies among participants in acupuncture clinical trials. We hypothesized that pressure pain tenderness would differentially classify treatment response to verum and sham acupuncture in fibromyalgia patients. Baseline pressure pain sensitivity at the thumbnail at baseline was used in linear mixed models as a modifier of differential treatment response to sham versus verum acupuncture. Similarly, needle-induced sensation was also analyzed to determine its differential effect of treatment on clinical pain. A cohort of 114 fibromyalgia patients received baseline pressure pain testing and were randomized to either verum (N = 59) or sham (N = 55) acupuncture. Participants received treatments from once a week to three times a week, increasing in three-week blocks for a total of 18 treatments. Clinical pain was measured on a 101-point visual analog scale, and needle sensation was measured by questionnaire throughout the trial. Participants who had higher pain pressure thresholds had greater reduction in clinical pain following verum acupuncture while participants who had lower pain pressure thresholds showed better analgesic response to sham acupuncture. Moreover, patients with lower pressure pain thresholds had exacerbated clinical pain following verum acupuncture. Similar relationships were observed for sensitivity to acupuncture needling. These findings suggest that acupuncture efficacy in fibromyalgia may be underestimated and a more personalized treatment for fibromyalgia may also be possible. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Intermittent but not sustained hypoxia activates orexin-containing neurons in mice.

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Yamaguchi, Keiji; Futatsuki, Takahiro; Ushikai, Jumpei; Kuroki, Chiharu; Minami, Toshiaki; Kakihana, Yasuyuki; Kuwaki, Tomoyuki

2015-01-15

Hypothalamic orexin-containing neurons are activated by CO2 and contribute to hypercapnic ventilatory activation. However, their role in oxygen-related regulation of breathing is not well defined. In this study, we examined whether an experimental model mimicking apnea-induced repetitive hypoxemia (intermittent hypoxia [IH]) activates orexin-containing neurons. Mice were exposed to IH (5×5min at 10% O2), intermittent hyperoxia (IO; 5×5min at 50% O2), sustained hypoxia (SH; 25min at 10% O2), or sham stimulation. Their brains were examined using double immunohistochemical staining for orexin and c-Fos. The results indicated that IH (25.8±3.0%), but not SH (9.0±1.5%) activated orexin-containing neurons when compared to IO (5.5±0.6%) and sham stimulation (5.9±1.4%). These results correlate with those of our previous work showing that IH-induced respiratory long-term facilitation is dependent on orexin-containing neurons. Taken together, orexin contributes to repetitive hypoxia-induced respiratory activation and the hypoxic activation of orexin-containing neurons is pattern dependent. Copyright © 2014 Elsevier B.V. All rights reserved.

Neurofeedback, sham neurofeedback, and cognitive-behavioural group therapy in adults with attention-deficit hyperactivity disorder: a triple-blind, randomised, controlled trial.

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Schönenberg, Michael; Wiedemann, Eva; Schneidt, Alexander; Scheeff, Jonathan; Logemann, Alexander; Keune, Philipp M; Hautzinger, Martin

2017-09-01

Many studies suggest that electroencephalographic (EEG) neurofeedback might be beneficial in the treatment of attention-deficit hyperactivity disorder (ADHD). However, numbers of well controlled studies are low and neurofeedback techniques are regarded as highly controversial. The present trial examined the efficacy (compared with sham neurofeedback) and efficiency (compared with meta-cognitive therapy) of a standard EEG neurofeedback protocol in adults with ADHD. We did a concurrent, triple-blind, randomised, controlled trial using authorised deception in adults with ADHD from one centre (University of Tübingen) in Tübingen, Germany. Participants were eligible if they fulfilled the DSM-IV-TR criteria for ADHD, were aged between 18 years and 60 years, and had no or stable use of medication for at least 2 months with no intention to change. We excluded participants who had comorbid schizophrenia or schizoaffective disorder, bipolar disorder, borderline personality disorder, epilepsy, or traumatic brain injury; substance abuse or dependence; or current or planned other psychological treatment. Those eligible were randomly assigned to three groups: a neurofeedback group which received 30 verum θ-to-β neurofeedback sessions over 15 weeks, a sham neurofeedback group which received 15 sham followed by 15 verum θ-to-β neurofeedback sessions over 15 weeks, or a meta-cognitive group therapy group which received 12 sessions over 12 weeks. Participants were assigned equally to one of the three interventions through a computerised minimisation randomisation procedure stratified by sex, age, and baseline symptom severity of ADHD. Participants were masked as to whether they were receiving neurofeedback or sham neurofeedback, but those receiving meta-cognitive therapy were aware of their treatment. Clinical assessors (ie, those assessing outcomes) and research staff who did the neurofeedback training were masked to participants' randomisation status only for neurofeedback

Diffuse traumatic axonal injury in mice induces complex behavioural alterations that are normalized by neutralization of interleukin-1β.

Science.gov (United States)

Ekmark-Lewén, Sara; Flygt, Johanna; Fridgeirsdottir, Gudrun A; Kiwanuka, Olivia; Hånell, Anders; Meyerson, Bengt J; Mir, Anis K; Gram, Hermann; Lewén, Anders; Clausen, Fredrik; Hillered, Lars; Marklund, Niklas

2016-04-01

Widespread traumatic axonal injury (TAI) results in brain network dysfunction, which commonly leads to persisting cognitive and behavioural impairments following traumatic brain injury (TBI). TBI induces a complex neuroinflammatory response, frequently located at sites of axonal pathology. The role of the pro-inflammatory cytokine interleukin (IL)-1β has not been established in TAI. An IL-1β-neutralizing or a control antibody was administered intraperitoneally at 30 min following central fluid percussion injury (cFPI), a mouse model of widespread TAI. Mice subjected to moderate cFPI (n = 41) were compared with sham-injured controls (n = 20) and untreated, naive mice (n = 9). The anti-IL-1β antibody reached the target brain regions in adequate therapeutic concentrations (up to ~30 μg/brain tissue) at 24 h post-injury in both cFPI (n = 5) and sham-injured (n = 3) mice, with lower concentrations at 72 h post-injury (up to ~18 μg/g brain tissue in three cFPI mice). Functional outcome was analysed with the multivariate concentric square field (MCSF) test at 2 and 9 days post-injury, and the Morris water maze (MWM) at 14-21 days post-injury. Following TAI, the IL-1β-neutralizing antibody resulted in an improved behavioural outcome, including normalized behavioural profiles in the MCSF test. The performance in the MWM probe (memory) trial was improved, although not in the learning trials. The IL-1β-neutralizing treatment did not influence cerebral ventricle size or the number of microglia/macrophages. These findings support the hypothesis that IL-1β is an important contributor to the processes causing complex cognitive and behavioural disturbances following TAI. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Computationally Developed Sham Stimulation Protocol for Multichannel Desynchronizing Stimulation

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Magteld Zeitler

2018-05-01

Full Text Available A characteristic pattern of abnormal brain activity is abnormally strong neuronal synchronization, as found in several brain disorders, such as tinnitus, Parkinson's disease, and epilepsy. As observed in several diseases, different therapeutic interventions may induce a placebo effect that may be strong and hinder reliable clinical evaluations. Hence, to distinguish between specific, neuromodulation-induced effects and unspecific, placebo effects, it is important to mimic the therapeutic procedure as precisely as possibly, thereby providing controls that actually lack specific effects. Coordinated Reset (CR stimulation has been developed to specifically counteract abnormally strong synchronization by desynchronization. CR is a spatio-temporally patterned multichannel stimulation which reduces the extent of coincident neuronal activity and aims at an anti-kindling, i.e., an unlearning of both synaptic connectivity and neuronal synchrony. Apart from acute desynchronizing effects, CR may cause sustained, long-lasting desynchronizing effects, as already demonstrated in pre-clinical and clinical proof of concept studies. In this computational study, we set out to computationally develop a sham stimulation protocol for multichannel desynchronizing stimulation. To this end, we compare acute effects and long-lasting effects of six different spatio-temporally patterned stimulation protocols, including three variants of CR, using a no-stimulation condition as additional control. This is to provide an inventory of different stimulation algorithms with similar fundamental stimulation parameters (e.g., mean stimulation rates but qualitatively different acute and/or long-lasting effects. Stimulation protocols sharing basic parameters, but inducing nevertheless completely different or even no acute effects and/or after-effects, might serve as controls to validate the specific effects of particular desynchronizing protocols such as CR. In particular, based on

An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan

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Tricia Hubbard-Turner, Erik A. Wikstrom, Sophie Guderian, Michael J. Turner

2015-09-01

Full Text Available We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL group, the transected anterior talofibular ligament (ATFL/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse’s lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011. Daily duration was different between the three running groups (p = 0.048. The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046 while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028 compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019 and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005. The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately.

Apparent failure of thymic epithelium transplants to alter the course of autoimmune disease in NZB/W mice

International Nuclear Information System (INIS)

Morrow, W.J.W.; Nayak, R.C.; Cooke, A.; Roitt, I.M.

1982-01-01

Thymic epithelium from neonatal DBA/2 mice (H-2sup(d)) was placed under the kidney capsule of 10- to 12-wk-old female NZB/W mice (H-2sup(d/z)). Donor epithelium, equivalent to 1-2 lobes of neonatal thymus, was either irradiated (1300 rad.) or cultured for 7 days in order to minimise host-versus-graft reactions. Histological examination showed that the epithelium repopulated and remained in place until the end of the experiment, with no sign of rejection. Despite this, the treated animals lived no longer than the untreated or sham operated controls. Levels of anti-nuclear antibody and serum IgM (normally highly elevated in these animals) were not significantly different in any group. (Auth.)

Fronteras del corazón shamánico. Azares y dilemas Qom. En: Avá, nº 16

OpenAIRE

Wright, Pablo

2009-01-01

En este artículo analizo dilemas y paradojas que plantea la modernidad en el caso de los Takshek Qom o tobas del oriente de Formosa (Argentina). Para ello me centro en la experiencia del lkillakte o corazón como uno de los núcleos vitales y existenciales de la persona. Allí se alojan las distintas clases de poder shamánico y también es sede de los pensamientos y las emociones. Me interesa explorar qué le pasa en términos simbólicos al corazón shamánico frente al ...

Renal Denervation Attenuates Progression of Atherosclerosis in Apolipoprotein E–Deficient Mice Independent of Blood Pressure Lowering

Science.gov (United States)

Wang, Hui; Wang, Jintao; Guo, Chiao; Luo, Wei; Kleiman, Kyle; Eitzman, Daniel T.

2016-01-01

The renal autonomic nervous system may contribute to hypertension and vascular disease. Although the effects of renal artery denervation on blood pressure lowering are controversial, there may be other beneficial vascular effects independent of blood pressure lowering. Bilateral renal denervation (RDN) or sham operation (SO) was performed in 14-week-old male apolipoprotein E–deficient mice on a Western diet starting at 10 weeks of age. Efficacy of RDN was confirmed by reduction of renal norepinephrine levels (SO: 3.8±0.1 versus RDN: 1.7±0.3 ng/mL; P<0.01) at 6 weeks after procedure. Compared with SO, RDN had no effect on blood pressure (SO: 101.0±2.4 versus RDN: 97.5±1.6 mm Hg; P=0.25), total cholesterol (SO: 536.7±28.5 versus RDN: 535.7±62.9 mg/dL; P=0.99), or triglycerides (SO: 83.7±3.5 versus RDN: 86.9±10.2 mg/dL; P=0.78). Quantification of atherosclerosis at 20 weeks of age demonstrated reduced atherosclerosis in mice receiving RDN compared with SO (arterial tree oil-red-O surface staining RDN: 4.2±0.5% versus SO: 6.3±0.7%; P<0.05). Reduced atherosclerosis was associated with increased smooth muscle cell content in atherosclerotic plaques (RDN: 13.3±2.1 versus SO: 8.1±0.6%; P<0.05). Serum levels of aldosterone, monocyte chemoattractant protein-1, and 8-isoprostane were lower in mice that received RDN compared with sham-operated mice (aldosterone; RDN: 206.8±33.2 versus SO: 405.5±59.4 pg/mL, P<0.05; monocyte chemoattractant protein-1; RDN: 51.7±7.9 versus SO: 91.71±4.6 pg/mL, P<0.05; 8-isoprostane; RDN: 331.9±38.2 versus SO: 468.5±42.0 pg/mL, P<0.05). RDN reduces progression of atherosclerosis in apolipoprotein E–deficient mice. These changes are associated with reduced aldosterone levels, monocyte chemoattractant protein-1, and markers of oxidative stress. PMID:25646301

Oral Administration of Fermented Soymilk Products Protects the Skin of Hairless Mice against Ultraviolet Damage

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Mitsuyoshi Kano

2016-08-01

Full Text Available The protective effect of isoflavones on skin damage from ultraviolet (UV radiation and their bioavailability were investigated in ovariectomized hairless mice fed diets composed of fermented soymilk containing aglycone forms of isoflavones or control soymilk containing glucose-conjugated forms of isoflavones. The erythema intensity of dorsal skin was significantly higher in ovariectomized mice than in sham-operated mice (p < 0.05. The erythema intensity and epidermal thickness of dorsal skin were significantly lower in the fermented soymilk diet group than in the control diet group (each p < 0.05. Levels of cyclobutane pyrimidine dimers in dorsal skin were significantly lower in the fermented soymilk diet group than in the control group (p < 0.05. Serum and dorsal skin isoflavone concentrations were significantly higher in the fermented soymilk diet group than in the soymilk diet group (p < 0.05. These results indicate that oral administration of a fermented soymilk diet increases isoflavone concentrations in the blood and skin, effectively scavenging the reactive oxygen species generated by UV irradiation and exerting an estrogen-like activity, with a consequent protective effect on skin photodamage in hairless mice.

Effect of chronic pain on fentanyl self-administration in mice.

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Carrie L Wade

Full Text Available The development of opioid addiction in subjects with established chronic pain is an area that is poorly understood. It is critically important to clearly understand the neurobiology associated with propensity toward conversion to addiction under conditions of chronic pain. To pose the question whether the presence of chronic pain influences motivation to self-administer opioids for reward, we applied a combination of rodent models of chronic mechanical hyperalgesia and opioid self-administration. We studied fentanyl self-administration in mice under three conditions that induce chronic mechanical hyperalgesia: inflammation, peripheral nerve injury, and repeated chemotherapeutic injections. Responding for fentanyl was compared among these conditions and their respective standard controls (naïve condition, vehicle injection or sham surgery. Acquisition of fentanyl self-administration behavior was reduced or absent in all three conditions of chronic hyperalgesia relative to control mice with normal sensory thresholds. To control for potential impairment in ability to learn the lever-pressing behavior or perform the associated motor tasks, all three groups were evaluated for acquisition of food-maintained responding. In contrast to the opioid, chronic hyperalgesia did not interfere with the reinforcing effect of food. These studies indicate that the establishment of chronic hyperalgesia is associated with reduced or ablated motivation to seek opioid reward in mice.

Adaptation and possible attenuation of Theileria parva-infected cells grown in irradiated mice

International Nuclear Information System (INIS)

Irvin, A.D.; Brown, C.G.D.; Stagg, D.A.; Kanhai, G.K.; Kimber, C.D.; Radley, D.E.

1976-01-01

Theileria parva-infected bovine lymphoid cells were taken from 8 cattle immediately after death from East Coast fever (ECF). Cells were inoculated into groups of irradiated Swiss and athymic nude mice. The irradiated mice were exposed to 800 rad doses from a 60 Co source. Cells became established in one group of Swiss mice and 2 groups of athymic mice. Development of cells in mice only occurred if cells concurrently established in culture; when establishment in culture was delayed, cells failed to develop in mice. Cells from one of the isolates in athymic mice were passaged 6 times through further mice. On inoculation of these mouse-passaged cells into cattle, the animals underwent mild reactions and subsequently resisted a lethal ECF challenge. The possibility of vaccinating cattle aginst ECF by means of mouse passaged cells merits further study. (author)

Effects of acute sublethal gamma radiation exposure on aggressive behavior in male mice: A dose-response study

International Nuclear Information System (INIS)

Maier, D.M.; Landauer, M.R.

1989-01-01

The resident-intruder paradigm was used to assess the effects of gamma radiation (0, 3, 5, 7 Gray [Gy] cobalt-60) on aggressive offensive behavior in resident male mice over a 3-month period. The defensive behavior of nonirradiated intruder mice was also monitored. A dose of 3 Gy had no effect on either the residents' offensive behavior or the defensive behavior of the intruders paired with them. Doses of 5 and 7 Gy produced decreases in offensive behavior of irradiated residents during the second week postirradiation. The nonirradiated intruders paired with these animals displayed decreases in defensive behavior during this time period, indicating a sensitivity to changes in the residents' behavior. After the third week postirradiation, offensive and defensive behavior did not differ significantly between irradiated mice and sham-irradiated controls. This study suggests that sublethal doses of radiation can temporarily suppress aggressive behavior but have no apparent permanent effect on that behavior

The effectiveness of moxibustion for the treatment of functional constipation: a randomized, sham-controlled, patient blinded, pilot clinical trial

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Park Ji-Eun

2011-12-01

Full Text Available Abstract Background Moxibustion is an ancient traditional medicine using burning mugworts to stimulate acupuncture points. The aim of this study was to investigate the safety and efficacy of moxibustion for the treatment of constipation using a randomized, sham-controlled, participant-blinded, pilot trial. Methods Twenty-six participants (identified with either qi (vital energy deficiency or qi excess syndrome were randomly divided into either a moxibustion or sham group. Participants were treated with real or sham moxibustion at 4 acupuncture points, ST23 and ST27, bilaterally, 3 times per week for four weeks. The primary outcome was the frequency of defecations; secondary outcomes were the Bristol stool form scale (BSS and the constipation assessment scale (CAS. Results Of the 26 participants that were randomized, 24 completed the study. Defecation frequency, BSS, and CAS showed no difference between the moxibustion and sham groups. The differences were -0.25 (95% CI: -2.08, 1.58, p = 0.78, -1.22 (95% CI: -2.7, 0.26, p = 0.1, 0.91 (95% CI: -1.46, 3.28, p = 0.44 in defecation frequency, BSS, CAS, respectively. The defecation frequency increased from an average of 3.3 to 4.6 times per week in the moxibustion group (1.5[-0.5, 2], p = 0.06 and from 2.7 to 3.7 stools per week in the sham group (1[-1, 2], p = 0.15 after four weeks of treatment. The difference between participants with a deficiency or an excess syndrome, determined based on assessment of sweat, facial features, pain, body energy, and pulse type, was significant in only defecation frequency. The difference was 3.3 (95% CI: 0.41, 6.19, p = 0.03. Conclusion Moxibustion treatment appears safe, but showed no positive effect on constipation. The effectiveness of moxibustion treatment may depend on the syndrome pattern, and further long-term studies with a larger number of subjects are warranted. Trial registration Clinical Research Information Service, KCT0000168

In vivo preclinical low field MRI monitoring of tumor growth following a suicide gene therapy in an ortho-topic mice model of human glioblastoma;Controle par IRM bas champ in vivo de l'efficacite d'une therapie genique par gene suicide dans un modele murin de glioblastome orthotopique

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Breton, E.; Goetz, Ch.; Aubertin, G.; Constantinesco, A.; Choquet, Ph. [Service de biophysique et medecine nucleaire, hopital de Hautepierre, CHRU de Strasbourg, 67 - Strasbourg (France); Institut de mecanique des fluides et des solides, CNRS, universite de Strasbourg, 67 - Strasbourg (France); Kintz, J.; Accart, N.; Grellier, B.; Erbs, Ph.; Rooke, R. [Transgene SA, parc d' innovation, 67 - Illkirch Graffenstaden (France)

2010-03-15

Purpose The aim of this study was to monitor in vivo with low field MRI growth of a murine ortho-topic glioma model following a suicide gene therapy. Methods The gene therapy consisted in the stereotactic injection in the mice brain of a modified vaccinia virus Ankara (M.V.A.) vector encoding for a suicide gene (FCU1) that transforms a non toxic pro-drug 5-fluoro-cytosine (5-F.C.) to its highly cytotoxic derivatives 5-fluorouracil (5-F.U.) and 5-fluoro-uridine-5 monophosphate (5-F.U.M.P.). Using a warmed-up imaging cell, sequential 3D T1 and T2 0.1T MRI brain examinations were performed on 16 Swiss female nu/nu mice bearing ortho-topic human glioblastoma (U 87-MG cells). The 6-week in vivo MRI follow-up consisted in a weekly measurement of the intracerebral tumor volume leading to a total of 65 examinations. Mice were divided in four groups: sham group (n = 4), sham group treated with 5-F.C. only (n = 4), sham group with injection of M.V.A.-FCU1 vector only (n = 4), therapy group administered with M.V.A.-FCU1 vector and 5-F.C. (n = 4). Measurements of tumor volumes were obtained after manual segmentation of T1- and T2-weighted images. Results Intra-observer and inter-observer tumor volume measurements show no significant differences. No differences were found between T1 and T2 volume tumor doubling times between the three sham groups. A significant statistical difference (p < 0.05) in T1 and T2 volume tumor doubling times between the three sham groups and the animals treated with the intratumoral injection of M.V.A.-FCU1 vector in combination with 2 weeks per os 5-F.C. administration was demonstrated. Conclusion Preclinical low field MRI was able to monitor efficacy of suicide gene therapy in delaying the tumor growth in an in vivo mouse model of ortho-topic glioblastoma. (authors)

Different mechanisms for the short-term effects of real versus sham transcutaneous electrical nerve stimulation (TENS) in patients with chronic pain: a pilot study.

Science.gov (United States)

Oosterhof, Jan; Wilder-Smith, Oliver H; Oostendorp, Rob A; Crul, Ben J

2012-01-01

Transcutaneous electrical nerve stimulation (TENS) has existed since the early 1970s. However, randomized placebo controlled studies show inconclusive results in the treatment of chronic pain. These results could be explained by assuming that TENS elicits a placebo response. However, in animal research TENS has been found to decrease hyperalgesia, which contradicts this assumption. The aim of this study is to use quantitative sensory testing to explore changes in pain processing during sham versus real TENS in patients with chronic pain. Patients with chronic pain (N = 20) were randomly allocated to real TENS or sham TENS application. Electrical pain thresholds (EPTs) were determined inside and outside the segment stimulated, before and after the first 20 minutes of the intervention, and after a period of 10 days of daily real/sham TENS application. Pain relief did not differ significantly for real versus sham TENS. However, by comparing time courses of EPTs, it was found that EPT values outside the segment of stimulation increased for sham TENS, whereas for real TENS these values decreased. There were, however, no differences for EPT measurements inside the segment stimulated. These results illustrate the importance of including mechanism-reflecting parameters in addition to symptoms when conducting pain research.

Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia

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Emerson, Nichole M.; Farris, Suzan R.; Ray, Jenna N.; Jung, Youngkyoo; McHaffie, John G.; Coghill, Robert C.

2015-01-01

Mindfulness meditation reduces pain in experimental and clinical settings. However, it remains unknown whether mindfulness meditation engages pain-relieving mechanisms other than those associated with the placebo effect (e.g., conditioning, psychosocial context, beliefs). To determine whether the analgesic mechanisms of mindfulness meditation are different from placebo, we randomly assigned 75 healthy, human volunteers to 4 d of the following: (1) mindfulness meditation, (2) placebo conditioning, (3) sham mindfulness meditation, or (4) book-listening control intervention. We assessed intervention efficacy using psychophysical evaluation of experimental pain and functional neuroimaging. Importantly, all cognitive manipulations (i.e., mindfulness meditation, placebo conditioning, sham mindfulness meditation) significantly attenuated pain intensity and unpleasantness ratings when compared to rest and the control condition (p Mindfulness meditation reduced pain intensity (p = 0.032) and pain unpleasantness (p Mindfulness meditation also reduced pain intensity (p = 0.030) and pain unpleasantness (p = 0.043) ratings more than sham mindfulness meditation. Mindfulness-meditation-related pain relief was associated with greater activation in brain regions associated with the cognitive modulation of pain, including the orbitofrontal, subgenual anterior cingulate, and anterior insular cortex. In contrast, placebo analgesia was associated with activation of the dorsolateral prefrontal cortex and deactivation of sensory processing regions (secondary somatosensory cortex). Sham mindfulness meditation-induced analgesia was not correlated with significant neural activity, but rather by greater reductions in respiration rate. This study is the first to demonstrate that mindfulness-related pain relief is mechanistically distinct from placebo analgesia. The elucidation of this distinction confirms the existence of multiple, cognitively driven, supraspinal mechanisms for pain

Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia.

Science.gov (United States)

Zeidan, Fadel; Emerson, Nichole M; Farris, Suzan R; Ray, Jenna N; Jung, Youngkyoo; McHaffie, John G; Coghill, Robert C

2015-11-18

Mindfulness meditation reduces pain in experimental and clinical settings. However, it remains unknown whether mindfulness meditation engages pain-relieving mechanisms other than those associated with the placebo effect (e.g., conditioning, psychosocial context, beliefs). To determine whether the analgesic mechanisms of mindfulness meditation are different from placebo, we randomly assigned 75 healthy, human volunteers to 4 d of the following: (1) mindfulness meditation, (2) placebo conditioning, (3) sham mindfulness meditation, or (4) book-listening control intervention. We assessed intervention efficacy using psychophysical evaluation of experimental pain and functional neuroimaging. Importantly, all cognitive manipulations (i.e., mindfulness meditation, placebo conditioning, sham mindfulness meditation) significantly attenuated pain intensity and unpleasantness ratings when compared to rest and the control condition (p pain intensity (p = 0.032) and pain unpleasantness (p pain intensity (p = 0.030) and pain unpleasantness (p = 0.043) ratings more than sham mindfulness meditation. Mindfulness-meditation-related pain relief was associated with greater activation in brain regions associated with the cognitive modulation of pain, including the orbitofrontal, subgenual anterior cingulate, and anterior insular cortex. In contrast, placebo analgesia was associated with activation of the dorsolateral prefrontal cortex and deactivation of sensory processing regions (secondary somatosensory cortex). Sham mindfulness meditation-induced analgesia was not correlated with significant neural activity, but rather by greater reductions in respiration rate. This study is the first to demonstrate that mindfulness-related pain relief is mechanistically distinct from placebo analgesia. The elucidation of this distinction confirms the existence of multiple, cognitively driven, supraspinal mechanisms for pain modulation. Recent findings have demonstrated that mindfulness meditation

Prenatal irradiation and spatial memory in mice: investigation of dose-response relationship

International Nuclear Information System (INIS)

Sienkiewicz, Z.J.; Haylock, R.G.E.; Saunders, R.D.

1994-01-01

Pregnant CD1 mice were exposed on gestational day 18 to 250 kV X-rays at 0.1, 0.25, 0.35 and 0.5 Gy. The performances of 10 adult male offspring from each exposure condition were investigated on a spatial discrimination learning task in a radial arm maze. An impairment in the performance of this task was found which showed a correlation with dose. Compared with sham exposed control mice, performance was not significantly affected with irradiation at 0.1 Gy and was slightly but non-significantly reduced at 0.25 Gy. Irradiation at 0.35 Gy caused a significant impairment in performance, and exposure at 0.5 Gy resulted in a still larger impairment. The overall association between dose and behavioural impairment was best described by a linear relationship without a threshold, although at doses lower than about 0.25 Gy any impairment would appear to be too small to be detectable. (Author)

Effect of Spinal Manipulation of Upper Cervical Vertebrae on Blood Pressure: Results of a Pilot Sham-Controlled Trial.

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Goertz, Christine M; Salsbury, Stacie A; Vining, Robert D; Long, Cynthia R; Pohlman, Katherine A; Weeks, William B; Lamas, Gervasio A

2016-06-01

The purpose of this pilot sham-controlled clinical trial was to estimate the treatment effect and safety of toggle recoil spinal manipulation for blood pressure management. Fifty-one participants with prehypertension or stage 1 hypertension (systolic blood pressure ranging from 135 to 159 mm Hg or diastolic blood pressure ranging from 85 to 99 mm Hg) were allocated by an adaptive design to 2 treatments: toggle recoil spinal manipulation or a sham procedure. Participants were seen by a doctor of chiropractic twice weekly for 6 weeks and remained on their antihypertensive medications, as prescribed, throughout the trial. Blood pressure was assessed at baseline and after study visits 1, 6 (week 3), and 12 (week 6), with the primary end point at week 6. Analysis of covariance was used to compare mean blood pressure changes from baseline between groups at each end point, controlling for sex, age, body mass index, and baseline blood pressure. Adjusted mean change from baseline to week 6 was greater in the sham group (systolic, -4.2 mm Hg; diastolic, -1.6 mm Hg) than in the spinal manipulation group (systolic, 0.6 mm Hg; diastolic, 0.7 mm Hg), but the difference was not statistically significant. No serious and few adverse events were noted. Six weeks of toggle recoil spinal manipulation did not lower systolic or diastolic blood pressure when compared with a sham procedure. No serious adverse events from either treatment were reported. Our results do not support a larger clinical trial. Further research to understand the potential mechanisms of action involving upper cervical manipulation on blood pressure is warranted before additional clinical investigations are conducted. Copyright © 2016. Published by Elsevier Inc.

Tritiated thymidine incorporation and the development of an interstitial lesion in the bronchiolar-alveolar regions of the lungs of normal and complement deficient mice after inhalation of chrysotile asbestos

International Nuclear Information System (INIS)

McGavran, P.D.; Butterick, C.J.; Brody, A.R.

1989-01-01

Inhaled asbestos causes the proliferation of bronchiolar-alveolar epithelial and interstitial cells in rats and mice 19 to 72 hours after a single 5-hour exposure. This condition is associated with rapid macrophage accumulation and development of an interstitial fibrotic lesion at alveolar duct bifurcations. In an attempt to define the mechanisms mediating asbestos-induced cell proliferation and fibrogenesis, we studied mice exposed to chrysotile asbestos for five hours. The mice were normal and a congenic strain (B10.D2/oSn), deficient in the fifth component of complement (C5-). We knew that the latter exhibit a depressed asbestos-induced macrophage response and wanted to learn whether the depressed response correlated with measurements of cell proliferation and progression of an interstitial lesion. Sections of first alveolar duct bifurcations were prepared for light microscopic autoradiography and ultrastructural morphometry at varying times after animal exposure to asbestos. In sham-exposed C5+ and C5- animals, less than 1% of epithelial and interstitial cells of the terminal bronchioles and alveolar ducts incorporated tritiated thymidine (3H-TdR) at any time after exposure to asbestos. Between 19 and 72 hours after exposure, epithelial and interstitial cells in both strains of mice exhibited significantly increased levels of 3H-TdR incorporation. The response decreased by eight days postexposure, and 3H-TdR incorporation was normal one month after exposure. Similarly, morphometry showed that both the C5+ and C5- asbestos-exposed mice exhibited significant increases in the volume density of epithelial and interstitial cells 48 hours after exposure. However, one month after exposure, the normal C5+ asbestos-exposed mice developed a fibrotic lesion, whereas the C5- asbestos-exposed animals were no different from sham-exposed C5- controls

[Noopept improves the spatial memory and stimulates prefibrillar beta-amyloid(25-35) antibody production in mice].

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Bobkova, N V; Gruden', M A; Samokhin, A N; Medvinskaia, N I; Morozova-Roch, L; Uudasheva, T A; Ostrovskaia, R U; Seredinin, S B

2005-01-01

The effects of the novel proline-containing nootropic and neuroprotective dipeptide noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were studied on NMRI mice upon olfactory bulbectomy, which had been previously shown to imitate the main morphological and biochemical signs of Alzheimer's disease (AD). The spatial memory was assessed using the Morris (water maze) test; the immunological status was characterized by ELISA with antibodies to prefibrillar beta-amyloid(25-35), S100b protein, and protofilaments of equine lysozyme, which are the molecular factors involved in the pathogenesis of AD. The control (sham-operated) animals during the Morris test preferred a sector where the safety platform was placed during the learning session. Bulbectomized animals treated with saline failed to recognize this sector, while bulbectomized animals treated with noopept (0.01 mg/kg for 21 days) restored this predominance, thus demonstrating the improvement of the spatial memory. These animals also demonstrated an increase in the level of antibodies to beta-amyloid(25-35)--the effect, which was more pronounced in the sham-operated than in bulbectomized mice. The latter demonstrated a profound decrease of immunological reactivity in a large number of tests. Noopept, stimulating the production of antibodies to beta-amyloid(25-35), can attenuate the well-known neurotoxic effects of beta-amyloid. The obtained data on the mnemotropic and immunostimulant effects noopept are indicative of good prospects for the clinical usage of this drug in the therapy of patients with neurodegenerative diseases.

Hydrogen-rich saline attenuates anxiety-like behaviors in morphine-withdrawn mice.

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Wen, Di; Zhao, Peng; Hui, Rongji; Wang, Jian; Shen, Qianchao; Gong, Miao; Guo, Hongyan; Cong, Bin; Ma, Chunling

2017-05-15

Hydrogen therapy is a new medical approach for a wide range of diseases. The effects of hydrogen on central nervous system-related diseases have recently become increasingly appreciated, but little is known about whether hydrogen affects the morphine withdrawal process. This study aims to investigate the potential effects of hydrogen-rich saline (HRS) administration on naloxone-precipitated withdrawal symptoms and morphine withdrawal-induced anxiety-like behaviors. Mice received gradually increasing doses (25-100 mg/kg, i.p.) of morphine over 3 days. In the naloxone-precipitated withdrawal procedure, the mice were treated with three HRS (20 μg/kg, i.p.) injections, and naloxone (1 mg/kg, i.p.) was given 30 min after HRS administration. Body weight, jumping behavior and wet-dog shakes were immediately assessed. In the spontaneous withdrawal procedure, the mice were treated with HRS (20 μg/kg, i.p.) every 8-h. Mice underwent naloxone-precipitated or spontaneous withdrawal were tested for anxiety-like behaviors in the elevated plus-maze (EPM) and light/dark box (L/D box) paradigm, respectively. In addition, the levels of plasma corticosterone were measured. We found that HRS administration significantly reduced body weight loss, jumping behavior and wet-dog shakes in mice underwent naloxone-precipitated withdrawal, and attenuated anxiety-like behaviors in the EPM and L/D box tests after naloxone-precipitated withdrawal or a 2-day spontaneous withdrawal period. Hypo-activity or motor impairment after HRS administration was not observed in the locomotion tests. Furthermore, HRS administration significantly decreased the levels of corticosterone in morphine-withdrawn mice. These are the first findings to indicate that hydrogen might ameliorate withdrawal symptoms and exert an anxiolytic-like effect in morphine-withdrawal mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Learning and memory in mice with neuropathic pain: impact of old age and progranulin deficiency

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Boris eAlbuquerque

2013-11-01

Full Text Available Persistent neuropathic pain is a frequent consequence of peripheral nerve injuries, particularly in the elderly. Using the IntelliCage we studied if a sciatic nerve injury obstructed learning and memory in young and aged mice, each in wild type and progranulin deficient mice, which develop premature signs of brain aging and are more susceptible to nerve injury evoked nociceptive hypersensitivity and hence allow to assess a potential mutual aggravation of pain and old age. Both young and aged mice developed long-term nerve injury-evoked hyperalgesia and allodynia but, in both genotypes, only aged mice with neuropathic pain showed high error rates in place avoidance acquisition tasks. Once learnt however, aged mice with neuropathic pain maintained the aversive memory longer, i.e. the extinction was significantly slowed. In addition, nerve injury in progranulin deficient mice impaired the learning of spatial sequences of awarded places, particularly in aged mice, whereas easy place preference learning was not affected by nerve injury or progranulin deficiency. The sequencing task required a discrimination of clockwise and anti-clockwise sequences and spatial flexibility to re-learn a novel sequence. The loss of spatial flexibility did not occur in sham operated mice, i.e. was a consequence of nerve injury and suggests that neuropathic pain accelerates manifestations of old age and progranulin deficiency. Neuropathic pain at old age, irrespective of the genotype, resulted in a long maintenance of aversive memory suggesting a negative alliance and possibly mutual aggravation of chronic neuropathic pain and aversive memory at old age.

Physical Meaning of Virtual Kohn-Sham Orbitals and Orbital Energies: An Ideal Basis for the Description of Molecular Excitations.

Science.gov (United States)

van Meer, R; Gritsenko, O V; Baerends, E J

2014-10-14

In recent years, several benchmark studies on the performance of large sets of functionals in time-dependent density functional theory (TDDFT) calculations of excitation energies have been performed. The tested functionals do not approximate exact Kohn-Sham orbitals and orbital energies closely. We highlight the advantages of (close to) exact Kohn-Sham orbitals and orbital energies for a simple description, very often as just a single orbital-to-orbital transition, of molecular excitations. Benchmark calculations are performed for the statistical average of orbital potentials (SAOP) functional for the potential [J. Chem. Phys. 2000, 112, 1344; 2001, 114, 652], which approximates the true Kohn-Sham potential much better than LDA, GGA, mGGA, and hybrid potentials do. An accurate Kohn-Sham potential does not only perform satisfactorily for calculated vertical excitation energies of both valence and Rydberg transitions but also exhibits appealing properties of the KS orbitals including occupied orbital energies close to ionization energies, virtual-occupied orbital energy gaps very close to excitation energies, realistic shapes of virtual orbitals, leading to straightforward interpretation of most excitations as single orbital transitions. We stress that such advantages are completely lost in time-dependent Hartree-Fock and partly in hybrid approaches. Many excitations and excitation energies calculated with local density, generalized gradient, and hybrid functionals are spurious. There is, with an accurate KS, or even the LDA or GGA potentials, nothing problematic about the "band gap" in molecules: the HOMO-LUMO gap is close to the first excitation energy (the optical gap).

Randomized sham-controlled, double-blind, multicenter clinical trial on the effect of percutaneous radiofrequency at the ramus communicans for lumbar disc pain.

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van Tilburg, C W J; Stronks, D L; Groeneweg, J G; Huygen, F J P M

2017-03-01

Investigate the effect of percutaneous radiofrequency compared to a sham procedure, applied to the ramus communicans for treatment of lumbar disc pain. Randomized sham-controlled, double-blind, crossover, multicenter clinical trial. Multidisciplinary pain centres of two general hospitals. Sixty patients aged 18 or more with medical history and physical examination suggestive for lumbar disc pain and a reduction of two or more on a numerical rating scale (0-10) after a diagnostic ramus communicans test block. Treatment group: percutaneous radiofrequency treatment applied to the ramus communicans; sham: same procedure except radiofrequency treatment. pain reduction. Secondary outcome measure: Global Perceived Effect. No statistically significant difference in pain level over time between the groups, as well as in the group was found; however, the factor period yielded a statistically significant result. In the crossover group, 11 out of 16 patients experienced a reduction in NRS of 2 or more at 1 month (no significant deviation from chance). No statistically significant difference in satisfaction over time between the groups was found. The independent factors group and period also showed no statistically significant effects. The same applies to recovery: no statistically significant effects were found. The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected. Post hoc analysis revealed that none of the investigated parameters contributed to the prediction of a significant pain reduction. Interrupting signalling through the ramus communicans may interfere with the transition of painful information from the discs to the central nervous system. Methodological differences exist in studies evaluating the efficacy of radiofrequency treatment for lumbar disc pain. A randomized, sham-controlled, double-blind, multicenter clinical trial on the effect of radiofrequency at the ramus

Sham surgery versus labral repair or biceps tenodesis for type II SLAP lesions of the shoulder: a three-armed randomised clinical trial.

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Schrøder, Cecilie Piene; Skare, Øystein; Reikerås, Olav; Mowinckel, Petter; Brox, Jens Ivar

2017-12-01

Labral repair and biceps tenodesis are routine operations for superior labrum anterior posterior (SLAP) lesion of the shoulder, but evidence of their efficacy is lacking. We evaluated the effect of labral repair, biceps tenodesis and sham surgery on SLAP lesions. A double-blind, sham-controlled trial was conducted with 118 surgical candidates (mean age 40 years), with patient history, clinical symptoms and MRI arthrography indicating an isolated type II SLAP lesion. Patients were randomly assigned to either labral repair (n=40), biceps tenodesis (n=39) or sham surgery (n=39) if arthroscopy revealed an isolated SLAP II lesion. Primary outcomes at 6 and 24 months were clinical Rowe score ranging from 0 to 100 (best possible) and Western Ontario Shoulder Instability Index (WOSI) ranging from 0 (best possible) to 2100. Secondary outcomes were Oxford Instability Shoulder Score, change in main symptoms, EuroQol (EQ-5D and EQ-VAS), patient satisfaction and complications. There were no significant between-group differences at any follow-up in any outcome. Between-group differences in Rowe scores at 2 years were: biceps tenodesis versus labral repair: 1.0 (95% CI -5.4 to 7.4), p=0.76; biceps tenodesis versus sham surgery: 1.6 (95% CI -5.0 to 8.1), p=0.64; and labral repair versus sham surgery: 0.6 (95% CI -5.9 to 7.0), p=0.86. Similar results-no differences between groups-were found for WOSI scores. Postoperative stiffness occurred in five patients after labral repair and in four patients after tenodesis. Neither labral repair nor biceps tenodesis had any significant clinical benefit over sham surgery for patients with SLAP II lesions in the population studied. ClinicalTrials.gov identifier: NCT00586742. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Sustained alterations of hypothalamic tanycytes during posttraumatic hypopituitarism in male mice.

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Osterstock, Guillaume; El Yandouzi, Taoufik; Romanò, Nicola; Carmignac, Danielle; Langlet, Fanny; Coutry, Nathalie; Guillou, Anne; Schaeffer, Marie; Chauvet, Norbert; Vanacker, Charlotte; Galibert, Evelyne; Dehouck, Bénédicte; Robinson, Iain C A F; Prévot, Vincent; Mollard, Patrice; Plesnila, Nikolaus; Méry, Pierre-François

2014-05-01

Traumatic brain injury is a leading cause of hypopituitarism, which compromises patients' recovery, quality of life, and life span. To date, there are no means other than standardized animal studies to provide insights into the mechanisms of posttraumatic hypopituitarism. We have found that GH levels were impaired after inducing a controlled cortical impact (CCI) in mice. Furthermore, GHRH stimulation enhanced GH to lower level in injured than in control or sham mice. Because many characteristics were unchanged in the pituitary glands of CCI mice, we looked for changes at the hypothalamic level. Hypertrophied astrocytes were seen both within the arcuate nucleus and the median eminence, two pivotal structures of the GH axis, spatially remote to the injury site. In the arcuate nucleus, GHRH neurons were unaltered. In the median eminence, injured mice exhibited unexpected alterations. First, the distributions of claudin-1 and zonula occludens-1 between tanycytes were disorganized, suggesting tight junction disruptions. Second, endogenous IgG was increased in the vicinity of the third ventricle, suggesting abnormal barrier properties after CCI. Third, intracerebroventricular injection of a fluorescent-dextran derivative highly stained the hypothalamic parenchyma only after CCI, demonstrating an increased permeability of the third ventricle edges. This alteration of the third ventricle might jeopardize the communication between the hypothalamus and the pituitary gland. In conclusion, the phenotype of CCI mice had similarities to the posttraumatic hypopituitarism seen in humans with intact pituitary gland and pituitary stalk. It is the first report of a pathological status in which tanycyte dysfunctions appear as a major acquired syndrome.

Towards a Kohn-Sham potential via the optimized effective-potential method

International Nuclear Information System (INIS)

Norman, M.R.; Koelling, D.D.

1984-01-01

The optimized effective-potential (OEP) method is applied to a self-interaction-corrected local-spin-density (SIC-LSD) energy functional. The local potential which results has the useful properties of being both self-interaction free and orbital independent, and it can thus be regarded as a good approximation to the exact Kohn-Sham potential. A number of atomic systems are examined in the exchange-only and in the Ceperley-Alder exchange-correlation approximations. The resulting total energies are very close to those obtained by previous applications of the LSD-SIC functional. The resultant potentials are structurally similar to those derived by applying the OEP method to a Hartree-Fock Hamiltonian: showing much improved behavior over the local-spin-density approximation in both large- and small-r regions as well as the characteristic intershell cusplike structure. The eigenvalues have less formal significance than the more standard approaches, especially those for unoccupied orbitals which seem to have no significance whatsoever. Nonetheless, the highest occupied eigenvalue agrees closely with the conventional LSD-SIC value. However, for the deeper levels, each eigenvalue lies higher than the comparable eigenvalue of the conventional SIC, although lower than the eigenvalue of the LSD potential: the deeper the level, the larger the difference. This property follows from the nonvariational character of the eigenvalues, and it is shown that one can obtain realistic excitation spectra from this formalism by utilizing the appropriate variational quantity. The results obtained illustrate some of the less understood issues in the application of the Kohn-Sham procedure within density-functional theory

Shams 1 - Design and operational experiences of the 100MW - 540°C CSP plant in Abu Dhabi

Science.gov (United States)

Alobaidli, Abdulaziz; Sanz, Borja; Behnke, Klaus; Witt, Thomas; Viereck, Detlef; Schwarz, Mark André

2017-06-01

SHAMS 1 ("Shams" means "Sun" in Arabic) Concentrated Solar Power plant is a very successful example of a modern plant, which combines the known configuration of a parabolic trough technology with the well-established power generation technologies operated at 540°C live steam temperature while respecting the specific requirement of the daily starts and shutdowns. In addition to the high live steam temperature challenge and being located in the middle of the desert approx. 120 km south west of the city of Abu Dhabi, the plant has to face, the plant has to fact several atmospheric challenges like the high dust concentration, wind storms, and high ambient temperature. This paper, written jointly by Shams Power Company - the project and operating company and MAN Diesel & Turbo - the steam turbine original manufacturer, describes the challenges in optimizing the design of the steam turbine to fulfill the requirement of fast start up while operating the plant on daily transient pattern for minimum 30 years. It also addresses the several atmospheric challenges and how the project and operating company has overcame them. Finally, the paper gives a snap shot on the operational experience and record of the plant showing that despite the very challenging environment, the budgeted target has been exceeded in the first two years of operation.

Protective effects of caffeoylxanthiazonoside isolated from fruits of Xanthium strumarium on sepsis mice.

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Wang, Yan-Hong; Li, Tie-Hua; Wu, Ben-Quan; Liu, Hui; Shi, Yun-Feng; Feng, Ding-Yun

2015-01-01

The fruit of Xanthium strumarium L. (Asteraceae) has been used for the treatment of various inflammatory diseases. This study investigates the protective effect of caffeoylxanthiazonoside (CYXD) isolated from fruits of X. strumarium on sepsis mice in vitro and in vivo. Cecal ligation and puncture (CLP) operation was used to establish the sepsis mice model, and sham mice were also performed. CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then the survival rate was measured in 96 h. Additionally, sepsis mice were induced by injection LPS (2 mg/kg); CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then mice were sacrificed, and serum levels of TNF-α and IL-6 were determined by ELISA assay. Furthermore, the ability of CYXD to neutralize LPS was measured by using the LAL test, and expressions of TNF-α, IL-6 were determined by using real-time fluorogenic PCR. Results indicated that CYXD significantly elevated survival rates of sepsis mice induced by CLP (p < 0.05) with survival rates of 35%, 45%, and 65%. Furthermore, the LPS level was decreased obviously by CYXD (1, 2, and 4 mg/L) (p < 0.05). Additionally, CYXD (10, 20, and 40 mg/kg) can not only significantly decrease TNF-α and IL-6 levels induced by LPS in mice's serum (p < 0.05), but also inhibit mRNA expressions of TNF-α and IL-6 induced by LPS in RAW 264.7 cells at doses of 20, 40, and 80 μg/mL (p < 0.05). Our study demonstrated that CYXD has significant protective effects on sepsis mice.

Experimental study of 99Tcm-HL91 and 99Tcm-MIBI in mice bearing Lewis lung cancer

International Nuclear Information System (INIS)

Han Chunqi; Li Yaming; Ren Yangang; Yi Lijie

2000-01-01

Objective: To evaluate the ability of detecting lung cancer by 99 Tc m -HL91 and 99 Tc m -MIBI in mice bearing Lewis lung cancer. Methods: Four model mice underwent whole body planar imaging at 2 h, 4 h after injection of 99 Tc m -MIBI; four mice underwent whole body planar imaging at 2 h and 4 h after injection of 99 Tc m -HL91, and the mice of the 99 Tc m -HL91 group were then killed, the tumor, blood and organs were removed, weighted and the radioactivity was measured. ROIs were drawn around the tumor, head and chest in whole body planar images, and radioactivity ratios of tumor to head (T/H), chest (T/C) and contralateral limbs (T/L) were calculated. Results: No significant tumor radioactivity in 2 h and 4 h images of 99 Tc m -MIBI mice (T/C: 0.20 +- 0.08 and 0.14 +- 0.07) was found; increased tumor radioactivity was identified in images of 99 Tc m -HL91 mice (T/C: 3.25 +- 1.25 and 2.44 +- 1.07), and there was significant difference (t = 4.8 - 7.5, P 99 Tc m -HL91 in tumor tissue of mice is higher and clearance rate is slower. 99 Tc m -HL91 is a valuable tumor imaging agent for clinical diagnosis for the cancer

Single hind limb burn injury to mice alters nuclear factor-κB expression and [¹⁸F] 2-fluoro-2-deoxy-D-glucose uptake.

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Carter, Edward A; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A; Jung, Walter; Tompkins, Ronald G; Fischman, Alan J

2014-01-01

Burn trauma to the extremities can produce marked systemic effects in mice. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism ([18F] 2-fluoro-2-deoxy-D-glucose [18FDG] uptake) by brown adipose tissue (BAT) and nuclear factor (NF)-κB activity in several tissues including skeletal muscle. This study examined the effect of a single hind limb burn in mice on 18FDG uptake by NF-κB activity in vivo, and blood flow was determined by laser Doppler techniques. Male NF-κB luciferase reporter mice (28-30 g) were anesthetized, both legs were shaven, and the right leg was subjected to scald injury by immersion in 90°C water for 5 seconds. Sham-treated animals were used as controls. Each burned and sham mouse was resuscitated with saline (2 mL, i.p.). The individual animals were placed in wire bottom cages with no food and free access to water. After 24 hours, the animals were imaged with laser Doppler for measuring blood flow in the hind limb. The animals were then unanesthetized with 50 μCi of FDG or luciferin (1.0 mg, i.v.) via tail vein. Five minutes after luciferin injection, NF-κB mice were studied by bioluminescence imaging with a charge-coupled device camera. One hour after 18FDG injection, the animals were killed with carbon dioxide overdose, and 18FDG biodistribution was measured. Tissues were also analyzed for NF-κB luciferase activity. The scalding procedure used here produced a full-thickness burn injury to the leg with sharp margins. 18FDG uptake by the burned leg was lower than that in the contralateral limb. Similarly, luciferase activity and blood flow in the burned leg were lower than those in the contralateral leg. 18FDG uptake by BAT and heart increased, whereas that by brain decreased. In conclusion, the present study suggests that burn injury to a single leg decreased FDG uptake by skeletal muscle but increased 18FDG uptake by BAT. The injury to the leg reduced NF-κB expression compared with the

Angiotensin AT2-receptor stimulation improves survival and neurological outcome after experimental stroke in mice

DEFF Research Database (Denmark)

Schwengel, Katja; Namsolleck, Pawel; Lucht, Kristin

2016-01-01

/BL6J or AT2R-knockout mice (AT2-KO) underwent MCAO for 30 min followed by reperfusion. Starting 45 min after MCAO, mice were treated once daily for 4 days with either vehicle or C21 (0.03 mg/kg ip). Neurological deficits were scored daily. Infarct volumes were measured 96 h post-stroke by MRI. C21...

Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia

Directory of Open Access Journals (Sweden)

Liyuan Chen

2018-03-01

Full Text Available Background: Fat deposition is associated with peripheral arterial disease. Adipose tissue has recently been implicated in vascular remodeling and angiogenic activity. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice.Methods: After 14 weeks of high-fat diet (HFD-fed mice, unilateral hind limb ischemia was performed. Subcutaneous white adipose tissue (WAT and brown adipose tissue (BAT fat pads were harvested from normal EGFP mice, and subcutaneously transplanted over the region of the adductor muscles of HFD mice. Blood flow was measured using Laser Doppler Scanner. Vascular density, macrophages infiltration, and macrophage polarization were examined by RT-qPCR, and immunohistochemistry.Results: We found that the transplantation of WAT derived from normal mice improved functional blood flow in HFD-fed mice compared to mice transplanted with BAT and sham-treated mice. WAT transplantation increased the recruitment of pericytes associated with nascent blood vessels, but did not affect capillary formation. Furthermore, transplantation of WAT ameliorated HFD-induced insulin resistance, M2 macrophage predominance and the release of arteriogenic factors in ischemic muscles. Mice receiving WAT also displayed a marked reduction in several proinflammatory cytokines. In contrast, mice transplanted with BAT were glucose intolerant and demonstrated increased IL-6 levels in ischemic muscles.Conclusion: These results indicate that transplantation of adipose tissue elicits improvements in blood perfusion and beneficial effects on systemic glucose homeostasis and could be a promising therapeutic option for the treatment of diabetic peripheral arterial disease.

Estrogen deficiency heterogeneously affects tissue specific stem cells in mice

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Kitajima, Yuriko; Doi, Hanako; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Kitajima, Michio; Miura, Kiyonori; Li, Tao-Sheng; Masuzaki, Hideaki

2015-01-01

Postmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17β-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17β-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type colonies in vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growth in vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders. PMID:26245252

Epidermal growth factor receptor restoration rescues the fatty liver regeneration in mice.

Science.gov (United States)

Zimmers, Teresa A; Jin, Xiaoling; Zhang, Zongxiu; Jiang, Yanlin; Koniaris, Leonidas G

2017-10-01

Hepatic steatosis is a common histological finding in obese patients. Even mild steatosis is associated with delayed hepatic regeneration and poor outcomes following liver resection or transplantation. We sought to identify and target molecular pathways that mediate this dysfunction. Lean mice and mice made obese through feeding of a high-fat, hypercaloric diet underwent 70 or 80% hepatectomy. After 70% resection, obese mice demonstrated 100% survival but experienced increased liver injury, reduced energy stores, reduced mitoses, increased necroapoptosis, and delayed recovery of liver mass. Increasing liver resection to 80% was associated with mortality of 40% in lean and 80% in obese mice ( P steatosis might promote liver regeneration and survival following hepatic resection or transplantation. Copyright © 2017 the American Physiological Society.

Effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice

International Nuclear Information System (INIS)

Huston, D.P.; Smathers, P.A.; Reeves, J.P.; Steinberg, A.D.

1983-01-01

The effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice were studied. Neonatally thymectomized male and female F1 mice reconstituted with a parental or F1-irradiated thymic lobe were compared to nonreconstituted and sham-thymectomized controls. While maleness retarded the spontaneous production of ss- and ds-DNA antibodies, thymic grafts did not suppress antibodies to ss-DNA in either sex, but did suppress the production of antibodies to ds-DNA in female mice. A unique property of NZB thymic grafts was the inability to suppress anti-RBC antibodies in male mice. Thus, (i) the gender of the F1 recipient was the most important determinant of production of antibodies to ss-DNA, (ii) either maleness or the thymic microenvironment could retard production of anti-ds-DNA antibodies, and (iii) both gender and the thymic microenvironment were important in the regulation of anti-RBC antibody production. Since the administration of thymosin did not suppress autoantibody production, the effects of the thymic grafts was not solely via thymic hormone production. These studies suggest that sex hormones and/or the thymic microenvironment can exert a suppressive effect on autoantibody production and that autoantibodies differ in their susceptibility to such suppression

Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

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Xiao-Bing Ji

2015-07-01

Full Text Available Background: Uncoupling protein 2 (UCP2 is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC, and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls. ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

Localization of Fibrinogen in the Vasculo-Astrocyte Interface after Cortical Contusion Injury in Mice

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Nino Muradashvili

2017-07-01

Full Text Available Besides causing neuronal damage, traumatic brain injury (TBI is involved in memory reduction, which can be a result of alterations in vasculo-neuronal interactions. Inflammation following TBI is involved in elevation of blood content of fibrinogen (Fg, which is known to enhance cerebrovascular permeability, and thus, enhance its deposition in extravascular space. However, the localization of Fg in the extravascular space and its possible interaction with nonvascular cells are not clear. The localization of Fg deposition in the extravascular space was defined in brain samples of mice after cortical contusion injury (CCI and sham-operation (control using immunohistochemistry and laser-scanning confocal microscopy. Memory changes were assessed with new object recognition and Y-maze tests. Data showed a greater deposition of Fg in the vascular and astrocyte endfeet interface in mice with CCI than in control animals. This effect was accompanied by enhanced neuronal degeneration and reduction in short-term memory in mice with CCI. Thus, our results suggest that CCI induces increased deposition of Fg in the vasculo-astrocyte interface, and is accompanied by neuronal degeneration, which may result in reduction of short-term memory.

Cadmium accelerates bone loss in ovariectomized mice and fetal rat limb bones in culture

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Bhattacharyya, M.H.; Whelton, B.D.; Stern, P.H.; Peterson, D.P.

1988-01-01

Loss of bone mineral after ovariectomy was studied in mice exposed to dietary cadmium at 0.25, 5, or 50 ppm. Results show that dietary cadmium at 50 ppm increased bone mineral loss to a significantly greater extent in ovariectomized mice than in sham-operated controls. These results were obtained from two studies, one in which skeletal calcium content was determined 6 months after ovariectomy and a second in which 45 Ca release from 45 Ca-prelabeled bones was measured immediately after the start of dietary cadmium exposure. Furthermore, experiments with 45 Ca-prelabeled fetal rat limb bones in culture demonstrated that Cd at 10 nM in the medium, a concentration estimated to be in the plasma of mice exposed to 50 ppm dietary Cd, strikingly increased bone resorption. These in vitro results indicate that cadmium may enhance bone mineral loss by a direct action on bone. Results of the in vivo studies are consistent with a significant role of cadmium in the etiology of Itai-Itai disease among postmenopausal women in Japan and may in part explain the increased risk of postmenopausal osteoporosis among women who smoke

Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice

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Woolbright, Benjamin L. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Jenkins, Rosalind E. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Bajt, Mary Lynn [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

2013-12-15

Cholestasis is a pathological common component of numerous liver diseases that results in hepatotoxicity, inflammation, and cirrhosis when untreated. While the predominant hypothesis in cholestatic liver injury remains hepatocyte apoptosis due to direct toxicity of hydrophobic bile acid exposure, recent work suggests that the injury occurs through inflammatory necrosis. In order to resolve this controversy, we used novel plasma biomarkers to assess the mechanisms of cell death during early cholestatic liver injury. C57Bl/6 mice underwent bile duct ligation (BDL) for 6–72 h, or sham operation. Another group of mice were given D-galactosamine and endotoxin as a positive control for apoptosis and inflammatory necrosis. Plasma levels of full length cytokeratin-18 (FL-K18), microRNA-122 (miR-122) and high mobility group box-1 protein (HMGB1) increased progressively after BDL with peak levels observed after 48 h. These results indicate extensive cell necrosis after BDL, which is supported by the time course of plasma alanine aminotransferase activities and histology. In contrast, plasma caspase-3 activity, cleaved caspase-3 protein and caspase-cleaved cytokeratin-18 fragments (cK18) were not elevated at any time during BDL suggesting the absence of apoptosis. In contrast, all plasma biomarkers of necrosis and apoptosis were elevated 6 h after Gal/End treatment. In addition, acetylated HMGB1, a marker for macrophage and monocyte activation, was increased as early as 12 h but mainly at 48–72 h. However, progressive neutrophil accumulation in the area of necrosis started at 6 h after BDL. In conclusion, these data indicate that early cholestatic liver injury in mice is an inflammatory event, and occurs through necrosis with little evidence for apoptosis. - Highlights: • The mechanism of cell death during cholestasis remains a controversial topic. • Plasma biomarkers offer new insight into cell death after bile duct ligation. • Cytokeratin-18, microRNA-122 and HMGB

Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice

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Woolbright, Benjamin L.; Antoine, Daniel J.; Jenkins, Rosalind E.; Bajt, Mary Lynn; Park, B. Kevin; Jaeschke, Hartmut

2013-01-01

Cholestasis is a pathological common component of numerous liver diseases that results in hepatotoxicity, inflammation, and cirrhosis when untreated. While the predominant hypothesis in cholestatic liver injury remains hepatocyte apoptosis due to direct toxicity of hydrophobic bile acid exposure, recent work suggests that the injury occurs through inflammatory necrosis. In order to resolve this controversy, we used novel plasma biomarkers to assess the mechanisms of cell death during early cholestatic liver injury. C57Bl/6 mice underwent bile duct ligation (BDL) for 6–72 h, or sham operation. Another group of mice were given D-galactosamine and endotoxin as a positive control for apoptosis and inflammatory necrosis. Plasma levels of full length cytokeratin-18 (FL-K18), microRNA-122 (miR-122) and high mobility group box-1 protein (HMGB1) increased progressively after BDL with peak levels observed after 48 h. These results indicate extensive cell necrosis after BDL, which is supported by the time course of plasma alanine aminotransferase activities and histology. In contrast, plasma caspase-3 activity, cleaved caspase-3 protein and caspase-cleaved cytokeratin-18 fragments (cK18) were not elevated at any time during BDL suggesting the absence of apoptosis. In contrast, all plasma biomarkers of necrosis and apoptosis were elevated 6 h after Gal/End treatment. In addition, acetylated HMGB1, a marker for macrophage and monocyte activation, was increased as early as 12 h but mainly at 48–72 h. However, progressive neutrophil accumulation in the area of necrosis started at 6 h after BDL. In conclusion, these data indicate that early cholestatic liver injury in mice is an inflammatory event, and occurs through necrosis with little evidence for apoptosis. - Highlights: • The mechanism of cell death during cholestasis remains a controversial topic. • Plasma biomarkers offer new insight into cell death after bile duct ligation. • Cytokeratin-18, microRNA-122 and HMGB

Acute cognitive impact of antiseizure drugs in naive rodents and corneal-kindled mice.

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Barker-Haliski, Melissa L; Vanegas, Fabiola; Mau, Matthew J; Underwood, Tristan K; White, H Steve

2016-09-01

Some antiseizure drugs (ASDs) are associated with cognitive liability in patients with epilepsy, thus ASDs without this risk would be preferred. Little comparative pharmacology exists with ASDs in preclinical models of cognition. Few pharmacologic studies exist on the acute effects in rodents with chronic seizures. Predicting risk for cognitive impact with preclinical models may supply valuable ASD differentiation data. ASDs (phenytoin [PHT]; carbamazepine [CBZ]; valproic acid [VPA]; lamotrigine [LTG]; phenobarbital [PB]; tiagabine [TGB]; retigabine [RTG]; topiramate [TPM]; and levetiracetam [LEV]) were administered equivalent to maximal electroshock median effective dose ([ED50]; mice, rats), or median dose necessary to elicit minimal motor impairment (median toxic dose [TD50]; rats). Cognition models with naive adult rodents were novel object/place recognition (NOPR) task with CF-1 mice, and Morris water maze (MWM) with Sprague-Dawley rats. Selected ASDs were also administered to rats prior to testing in an open field. The effect of chronic seizures and ASD administration on cognitive performance in NOPR was also determined with corneal-kindled mice. Mice that did not achieve kindling criterion (partially kindled) were included to examine the effect of electrical stimulation on cognitive performance. Sham-kindled and age-matched mice were also tested. No ASD (ED50) affected latency to locate the MWM platform; TD50 of PB, RTG, TPM, and VPA reduced this latency. In naive mice, CBZ and VPA (ED50) reduced time with the novel object. Of interest, no ASD (ED50) affected performance of fully kindled mice in NOPR, whereas CBZ and LEV improved cognitive performance of partially kindled mice. Standardized approaches to the preclinical evaluation of an ASD's potential cognitive impact are needed to inform drug development. This study demonstrated acute, dose- and model-dependent effects of therapeutically relevant doses of ASDs on cognitive performance of naive mice and

Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice

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Hernán H. Dieguez

2018-02-01

Full Text Available Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age

Self-Administered Domiciliary tDCS Treatment for Tinnitus: A Double-Blind Sham-Controlled Study.

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Petteri Hyvärinen

Full Text Available Transcranial direct current stimulation (tDCS has shown potential for providing tinnitus relief, although positive effects have usually been observed only during a short time period after treatment. In recent studies the focus has turned from one-session experiments towards multi-session treatment studies investigating long-term outcomes with double-blinded and sham-controlled study designs. Traditionally, tDCS has been administered in a clinical setting by a healthcare professional but in studies involving multiple treatment sessions, often a trade-off has to be made between sample size and the amount of labor needed to run the trial. Also, as the number of required visits to the clinic increases, the dropout rate is likely to rise proportionally.The aim of the current study was to find out if tDCS treatment for tinnitus could be patient-administered in a domiciliary setting and whether the results would be comparable to those from in-hospital treatment studies. Forty-three patients with chronic (> 6 months tinnitus were involved in the study, and data on 35 out of these patients were included in final analysis. Patients received 20 minutes of left temporal area anodal (LTA or bifrontal tDCS stimulation (2 mA or sham stimulation (0.3 mA for ten consecutive days. An overall reduction in the main outcome measure, Tinnitus Handicap Inventory (THI, was found (mean change -5.0 points, p < 0.05, but there was no significant difference between active and sham treatment outcomes. Patients found the tDCS treatment easy to administer and they all tolerated it well. In conclusion, self-administered domiciliary tDCS treatment for tinnitus was found safe and feasible and gave outcome results similar to recent randomized controlled long-term treatment trials. The results suggest better overall treatment response-as measured by THI-with domiciliary treatment than with in-hospital treatment, but this advantage is not related to the tDCS variant. The study

The Use of Trust Regions in Kohn-Sham Total Energy Minimization

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Yang, Chao; Meza, Juan C.; Wang, Lin-wang

2006-01-01

The Self Consistent Field (SCF) iteration, widely used for computing the ground state energy and the corresponding single particle wave functions associated with a many-electron atomistic system, is viewed in this paper as an optimization procedure that minimizes the Kohn-Sham total energy indirectly by minimizing a sequence of quadratic surrogate functions. We point out the similarity and difference between the total energy and the surrogate, and show how the SCF iteration can fail when the minimizer of the surrogate produces an increase in the KS total energy. A trust region technique is introduced as a way to restrict the update of the wave functions within a small neighborhood of an approximate solution at which the gradient of the total energy agrees with that of the surrogate. The use of trust region in SCF is not new. However, it has been observed that directly applying a trust region based SCF(TRSCF) to the Kohn-Sham total energy often leads to slow convergence. We propose to use TRSCF within a direct constrained minimization(DCM) algorithm we developed in dcm. The key ingredients of the DCM algorithm involve projecting the total energy function into a sequence of subspaces of small dimensions and seeking the minimizer of the total energy function within each subspace. The minimizer of a subspace energy function, which is computed by TRSCF, not only provides a search direction along which the KS total energy function decreases but also gives an optimal 'step-length' that yields a sufficient decrease in total energy. A numerical example is provided to demonstrate that the combination of TRSCF and DCM is more efficient than SCF

High frequency chest wall oscillation for asthma and chronic obstructive pulmonary disease exacerbations: a randomized sham-controlled clinical trial

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Lewis Stephanie

2011-09-01

Full Text Available Abstract Background High frequency chest wall oscillation (HFCWO is used for airway mucus clearance. The objective of this study was to evaluate the use of HFCWO early in the treatment of adults hospitalized for acute asthma or chronic obstructive pulmonary disease (COPD. Methods Randomized, multi-center, double-masked phase II clinical trial of active or sham treatment initiated within 24 hours of hospital admission for acute asthma or COPD at four academic medical centers. Patients received active or sham treatment for 15 minutes three times a day for four treatments. Medical management was standardized across groups. The primary outcomes were patient adherence to therapy after four treatments (minutes used/60 minutes prescribed and satisfaction. Secondary outcomes included change in Borg dyspnea score (≥ 1 unit indicates a clinically significant change, spontaneously expectorated sputum volume, and forced expired volume in 1 second. Results Fifty-two participants were randomized to active (n = 25 or sham (n = 27 treatment. Patient adherence was similarly high in both groups (91% vs. 93%; p = 0.70. Patient satisfaction was also similarly high in both groups. After four treatments, a higher proportion of patients in the active treatment group had a clinically significant improvement in dyspnea (70.8% vs. 42.3%, p = 0.04. There were no significant differences in other secondary outcomes. Conclusions HFCWO is well tolerated in adults hospitalized for acute asthma or COPD and significantly improves dyspnea. The high levels of patient satisfaction in both treatment groups justify the need for sham controls when evaluating the use of HFCWO on patient-reported outcomes. Additional studies are needed to more fully evaluate the role of HFCWO in improving in-hospital and post-discharge outcomes in this population. Trial Registration ClinicalTrials.gov: NCT00181285

Placebo effects of a sham opioid solution: a randomized controlled study in patients with chronic low back pain.

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Klinger, Regine; Kothe, Ralph; Schmitz, Julia; Kamping, Sandra; Flor, Herta

2017-10-01

This study tested the experimental placebo effect in a group of chronic pain patients. Forty-eight patients having chronic back pain participated in a randomized clinical trial that tested the efficacy of a sham opioid solution (NaCl) compared with an alleged neutral, completely inactive solution (NaCl). We shaped the placebo effect by 2 interventions: verbal instruction and conditioning. The patients were either told that the "solution reduces pain and improves physical capacity" or the "solution is neutral, a placebo." Half of each group was additionally conditioned (coupling solution with reduced experimental pain), yielding 4 subgroups with 12 participants each. Outcome measures were as follows: the patients' clinical back pain ratings and acute pain ratings (both examined by numerical rating scale 0-10) and self-rated functional capacity (0%-100%; time required for the exercise). Expected pain relief before and after solution intake was also assessed. The inactive solution (NaCl), when presented as an effective treatment (sham "opioid" solution), induced placebo analgesia as evident in lower ratings of the patients' clinical back pain (F(3.12,144.21) = 25.05, P pain ratings (F(1.99,87.40) = 18.12, P pain expectations, and they were maintained in both sham opioid groups. The results suggest that it may be clinically useful to explicitly integrate placebo analgesia responses into pain management.

A mouse model for chronic pain-induced increase in ethanol consumption.

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Butler, Ryan K; Knapp, Darin J; Ulici, Veronica; Longobardi, Lara; Loeser, Richard F; Breese, George R

2017-03-01

Chronic pain conditions are often comorbid with alcohol abuse. "Self-medication" with alcohol introduces a host of problems associated with the abuse of alcohol which over time has the potential of exacerbating the painful condition. Despite the prevalence of chronic pain being associated with alcohol abuse, rodent models which mimic the comorbid conditions are lacking. In this study, we model osteoarthritis (OA) in C57BL/6J mice by surgically destabilizing the medial meniscus (DMM). Sham-operated mice served as controls. Thirteen weeks after surgery, DMM but not sham-operated mice exhibited pronounced incapacitance of the surgically manipulated hind limb compared with the nonsurgically manipulated hind limb. At this time, the mice were exposed to the 2-bottle ethanol choice, beginning with 2.5% with a gradual increasing to 20%. Compared with sham controls, DMM mice consumed more EtOH and preferred EtOH over water at the 20% EtOH concentration. Histological analysis verified that the DMM mice exhibited significant damage to the articular cartilage and osteophyte growth compared with sham controls and these measures of the severity of OA correlated with the amount of ethanol intake. Thus, the combination of the DMM model of OA with the enhanced two-bottle ethanol choice is a potential preclinical approach in mice by which the basis of the comorbid association of alcohol abuse and chronic pain conditions can be explored.

On the relation between the Hartree-Fock and Kohn-Sham approaches

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Amusia, M.Ya. [Racah Institute of Physics, Hebrew University, 91904 Jerusalem (Israel); A.F. Ioffe Physical-Technical Institute, 194021 St. Petersburg (Russian Federation); Msezane, A.Z. [CTSPS, Clark Atlanta University, Atlanta, GA 30314 (United States); Shaginyan, V.R. [CTSPS, Clark Atlanta University, Atlanta, GA 30314 (United States); Petersburg Nuclear Physics Institute, 188300 Gatchina (Russian Federation)]. E-mail: vrshag@thd.pnpi.spb.ru; Sokolovski, D. [Queen' s University of Belfast, Belfast BT7 1NN (United Kingdom)

2004-09-13

We show that the Hartree-Fock (HF) results cannot be reproduced within the framework of Kohn-Sham (KS) theory because the single-particle densities of finite systems obtained within the HF calculations are not v-representable, i.e., do not correspond to any ground state of a N non-interacting electron systems in a local external potential. For this reason, the KS theory, which finds a minimum on a different subset of all densities, can overestimate the ground state energy, as compared to the HF result. The discrepancy between the two approaches provides no grounds to assume that either the KS theory or the density functional theory suffers from internal contradictions.

On the relation between the Hartree-Fock and Kohn-Sham approaches

International Nuclear Information System (INIS)

Amusia, M.Ya.; Msezane, A.Z.; Shaginyan, V.R.; Sokolovski, D.

2004-01-01

We show that the Hartree-Fock (HF) results cannot be reproduced within the framework of Kohn-Sham (KS) theory because the single-particle densities of finite systems obtained within the HF calculations are not v-representable, i.e., do not correspond to any ground state of a N non-interacting electron systems in a local external potential. For this reason, the KS theory, which finds a minimum on a different subset of all densities, can overestimate the ground state energy, as compared to the HF result. The discrepancy between the two approaches provides no grounds to assume that either the KS theory or the density functional theory suffers from internal contradictions

Charge transfer excitations from exact and approximate ensemble Kohn-Sham theory

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Gould, Tim; Kronik, Leeor; Pittalis, Stefano

2018-05-01

By studying the lowest excitations of an exactly solvable one-dimensional soft-Coulomb molecular model, we show that components of Kohn-Sham ensembles can be used to describe charge transfer processes. Furthermore, we compute the approximate excitation energies obtained by using the exact ensemble densities in the recently formulated ensemble Hartree-exchange theory [T. Gould and S. Pittalis, Phys. Rev. Lett. 119, 243001 (2017)]. Remarkably, our results show that triplet excitations are accurately reproduced across a dissociation curve in all cases tested, even in systems where ground state energies are poor due to strong static correlations. Singlet excitations exhibit larger deviations from exact results but are still reproduced semi-quantitatively.

Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice.

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Raber, Jacob; Torres, Eileen Ruth S; Akinyeke, Tunde; Lee, Joanne; Weber Boutros, Sydney J; Turker, Mitchell S; Kronenberg, Amy

2018-04-20

The space radiation environment includes helium (⁴He) ions that may impact brain function. As little is known about the effects of exposures to ⁴He ions on the brain, we assessed the behavioral and cognitive performance of C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation with ⁴He ions (250 MeV/n; linear energy transfer (LET) = 1.6 keV/μm; 0, 21, 42 or 168 cGy). Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not. In the passive avoidance test, mice received a slight foot shock in a dark compartment, and latency to re-enter that compartment was assessed 24 h later. Sham-irradiated mice and mice irradiated with 21 or 42 cGy showed a higher latency on Day 2 than Day 1, but the latency to enter the dark compartment in mice irradiated with 168 cGy was comparable on both days. ⁴He ion irradiation, at 42 and 168 cGy, reduced the levels of the dendritic marker microtubule-associated protein-2 (MAP-2) in the cortex. There was an effect of radiation on apolipoprotein E (apoE) levels in the hippocampus and cortex, with higher apoE levels in mice irradiated at 42 cGy than 168 cGy and a trend towards higher apoE levels in mice irradiated at 21 than 168 cGy. In addition, in the hippocampus, there was a trend towards a negative correlation between MAP-2 and apoE levels. While reduced levels of MAP-2 in the cortex might have contributed to the altered performance in the passive avoidance test, it does not seem sufficient to do so. The higher hippocampal and cortical apoE levels in mice irradiated at 42 than 168 cGy might have served as a compensatory protective response preserving their passive avoidance memory. Thus, there were no alterations in behavioral performance in the open filed or depressive-like behavior in the forced swim test, while cognitive impairments were seen in the object recognition and passive avoidance tests, but not in the contextual or cued fear

Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice

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Jacob Raber

2018-04-01

Full Text Available The space radiation environment includes helium (4He ions that may impact brain function. As little is known about the effects of exposures to 4He ions on the brain, we assessed the behavioral and cognitive performance of C57BL/6J × DBA2/J F1 (B6D2F1 mice three months following irradiation with 4He ions (250 MeV/n; linear energy transfer (LET = 1.6 keV/μm; 0, 21, 42 or 168 cGy. Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not. In the passive avoidance test, mice received a slight foot shock in a dark compartment, and latency to re-enter that compartment was assessed 24 h later. Sham-irradiated mice and mice irradiated with 21 or 42 cGy showed a higher latency on Day 2 than Day 1, but the latency to enter the dark compartment in mice irradiated with 168 cGy was comparable on both days. 4He ion irradiation, at 42 and 168 cGy, reduced the levels of the dendritic marker microtubule-associated protein-2 (MAP-2 in the cortex. There was an effect of radiation on apolipoprotein E (apoE levels in the hippocampus and cortex, with higher apoE levels in mice irradiated at 42 cGy than 168 cGy and a trend towards higher apoE levels in mice irradiated at 21 than 168 cGy. In addition, in the hippocampus, there was a trend towards a negative correlation between MAP-2 and apoE levels. While reduced levels of MAP-2 in the cortex might have contributed to the altered performance in the passive avoidance test, it does not seem sufficient to do so. The higher hippocampal and cortical apoE levels in mice irradiated at 42 than 168 cGy might have served as a compensatory protective response preserving their passive avoidance memory. Thus, there were no alterations in behavioral performance in the open filed or depressive-like behavior in the forced swim test, while cognitive impairments were seen in the object recognition and passive avoidance tests, but not in the contextual or cued

The Effects of Acupuncture at Real or Sham Acupoints on the Intrinsic Brain Activity in Mild Cognitive Impairment Patients

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Baohui Jia

2015-01-01

Full Text Available Accumulating neuroimaging studies in humans have shown that acupuncture can modulate a widely distributed brain network in mild cognitive impairment (MCI and Alzheimer’s disease (AD patients. Acupuncture at different acupoints could exert different modulatory effects on the brain network. However, whether acupuncture at real or sham acupoints can produce different effects on the brain network in MCI or AD patients remains unclear. Using resting-state fMRI, we reported that acupuncture at Taixi (KI3 induced amplitude of low-frequency fluctuation (ALFF change of different brain regions in MCI patients from those shown in the healthy controls. In MCI patients, acupuncture at KI3 increased or decreased ALFF in the different regions from those activated by acupuncture in the healthy controls. Acupuncture at the sham acupoint in MCI patients activated the different brain regions from those in healthy controls. Therefore, we concluded that acupuncture displays more significant effect on neuronal activities of the above brain regions in MCI patients than that in healthy controls. Acupuncture at KI3 exhibits different effects on the neuronal activities of the brain regions from acupuncture at sham acupoint, although the difference is only shown at several regions due to the close distance between the above points.

From the Kohn-Sham band gap to the fundamental gap in solids. An integer electron approach.

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Baerends, E J

2017-06-21

It is often stated that the Kohn-Sham occupied-unoccupied gap in both molecules and solids is "wrong". We argue that this is not a correct statement. The KS theory does not allow to interpret the exact KS HOMO-LUMO gap as the fundamental gap (difference (I - A) of electron affinity (A) and ionization energy (I), twice the chemical hardness), from which it indeed differs, strongly in molecules and moderately in solids. The exact Kohn-Sham HOMO-LUMO gap in molecules is much below the fundamental gap and very close to the much smaller optical gap (first excitation energy), and LDA/GGA yield very similar gaps. In solids the situation is different: the excitation energy to delocalized excited states and the fundamental gap (I - A) are very similar, not so disparate as in molecules. Again the Kohn-Sham and LDA/GGA band gaps do not represent (I - A) but are significantly smaller. However, the special properties of an extended system like a solid make it very easy to calculate the fundamental gap from the ground state (neutral system) band structure calculations entirely within a density functional framework. The correction Δ from the KS gap to the fundamental gap originates from the response part v resp of the exchange-correlation potential and can be calculated very simply using an approximation to v resp . This affords a calculation of the fundamental gap at the same level of accuracy as other properties of crystals at little extra cost beyond the ground state bandstructure calculation. The method is based on integer electron systems, fractional electron systems (an ensemble of N- and (N + 1)-electron systems) and the derivative discontinuity are not invoked.

Online and offline effects of cerebellar transcranial direct current stimulation on motor learning in healthy older adults: a randomized double-blind sham-controlled study.

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Samaei, Afshin; Ehsani, Fatemeh; Zoghi, Maryam; Hafez Yosephi, Mohaddese; Jaberzadeh, Shapour

2017-05-01

The aim of this randomized double blinded sham-controlled study was to determine the effect of cerebellar anodal transcranial direct current stimulation (a-tDCS) on online and offline motor learning in healthy older individuals. Thirty participants were randomly assigned in experimental (n = 15) or sham tDCS (n = 15) groups. Participants in experimental group received 2 mA cerebellar a-tDCS for 20 min. However, the tDCS was turned off after 30 seconds in sham group. Response time (RT) and error rate (ER) in serial RT test were assessed before, during 35 minutes and 48 h after the intervention. Reduction of RT and ER following the intervention session was considered as short-term (35 min post intervention) and long-term offline learning (48 h post intervention), respectively. Online RT and ER reduction were similar in both groups (P > 0.05). RT was significantly reduced 48 hours post intervention in cerebellar a-tDCS group (P = 0.03). Moreover, RT was significantly increased after 35 minutes and 48 hours in sham tDCS group (P = 0.03, P = 0.007), which indicates a lack of short-term and long-term offline learning in older adults. A-tDCS on cerebellar region produced more short-term and long-term offline improvement in RT (P = 0.014, P = 0.01) compared to sham tDCS. In addition, online, short-term and long-term (48 h) offline error reduced in cerebellar a-tDCS as compared to sham-control group, although this reduction was not significant (P > 0.05). A deficit suggests that a direct comparison to a younger group was made. The findings suggested that cerebellar a-tDCS might be useful for improvement of offline motor learning in older individuals. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Finite element method for solving Kohn-Sham equations based on self-adaptive tetrahedral mesh

International Nuclear Information System (INIS)

Zhang Dier; Shen Lihua; Zhou Aihui; Gong Xingao

2008-01-01

A finite element (FE) method with self-adaptive mesh-refinement technique is developed for solving the density functional Kohn-Sham equations. The FE method adopts local piecewise polynomials basis functions, which produces sparsely structured matrices of Hamiltonian. The method is well suitable for parallel implementation without using Fourier transform. In addition, the self-adaptive mesh-refinement technique can control the computational accuracy and efficiency with optimal mesh density in different regions

Randomized clinical trial of percutaneous tibial nerve stimulation versus sham electrical stimulation in patients with faecal incontinence.

Science.gov (United States)

van der Wilt, A A; Giuliani, G; Kubis, C; van Wunnik, B P W; Ferreira, I; Breukink, S O; Lehur, P A; La Torre, F; Baeten, C G M I

2017-08-01

The aim was to assess the effects of percutaneous tibial nerve stimulation (PTNS) in the treatment of faecal incontinence (FI) by means of an RCT. Patients aged over 18 years with FI were included in a multicentre, single-blinded RCT. The primary endpoint was reduction in the median or mean number of FI episodes per week. Secondary endpoints were changes in measures of FI severity, and disease-specific and generic quality of life. Outcomes were compared between PTNS and sham stimulation after 9 weeks of treatment. A higher proportion of patients in the PTNS (13 of 29) than in the sham (6 of 30) group showed a reduction of at least 50 per cent in the median number of FI episodes/week (incidence rate ratio (IRR) 2·40, 95 per cent c.i. 1·10 to 5·24; P = 0·028), but not in the mean number of episodes/week (10 of 29 versus 8 of 30; IRR 1·42, 0·69 to 2·92; P = 0·347). The absolute median number of FI episodes per week decreased in the PTNS but not in the sham group (IRR 0·66, 0·44 to 0·98; P = 0·041), as did the mean number (IRR 0·65 (0·45 to 0·97); P = 0·034). Scores on the Cleveland Clinic Florida faecal incontinence scale decreased significantly in both groups, but more steeply in the PTNS group (mean difference -1·3, 95 per cent c.i. -2·6 to 0·0; P = 0·049). The aggregated mental component score of Short Form 36 improved in the PTNS but not in the sham group (mean difference 5·1, 0·5 to 9·6; P = 0·028). PTNS may offer a small advantage in the clinical management of FI that is insufficiently responsive to conservative treatment. The key challenge will be to identify patients who may benefit most from this minimally invasive surgical procedure. Registration number: NCT00974909 (http://www.clinicaltrials.gov). © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice

International Nuclear Information System (INIS)

Geest, Rick van der; Ouweneel, Amber B.; Sluis, Ronald J. van der; Groen, Albert K.; Van Eck, Miranda; Hoekstra, Menno

2016-01-01

Cholestatic liver disease is characterized by a disruption of bile flow, bile acid toxicity, liver injury, and hypercholesterolemia. Relatively high secretion of glucocorticoids by the adrenals has been observed under cholestatic conditions. Here we investigated a contribution of the rise in endogenous glucocorticoids to initial stage cholestasis pathology. Adrenalectomized or sham-operated control C57BL/6 mice were given an oral dose of alpha-naphthylisothiocyanate to induce cholestasis. Adrenalectomy effectively lowered plasma corticosterone levels (18 ± 5 ng/ml vs 472 ± 58 ng/ml; P < 0.001) and disrupted the metabolic and anti-inflammatory glucocorticoid function. Adrenal removal did not exacerbate the cholestasis extent. In contrast, the cholestasis-associated liver injury was markedly lower in adrenalectomized mice as compared to controls as evidenced by a 84%–93% decrease in liver necrosis and plasma alanine aminotransferase and bile acid levels (P < 0.001 for all). Gene expression analysis on livers from adrenalectomized mice suggested the absence of bile acid toxicity-associated farnesoid X receptor signaling in the context of a 44% (P < 0.01) and 82% (P < 0.001) reduction in sodium/bile acid cotransporter member 1 transcript level as compared to respectively control and non-diseased mice. Adrenalectomy reduced the expression of the cholesterol synthesis gene HMG-CoA reductase by 70% (P < 0.05), which translated into a 73% lower plasma total cholesterol level (P < 0.05). Treatment of C57BL/6 mice with the glucocorticoid receptor antagonist RU-486 recapitulated the protective effect of adrenalectomy on indices of liver injury and hypercholesterolemia. In conclusion, we have shown that endogenous glucocorticoids exacerbate the liver injury and hypercholesterolemia associated with acute cholestasis in mice. - Highlights: • Cholestasis is associated with increased plasma glucocorticoid levels in mice. • Adrenalectomy lowers cholestasis-associated liver

Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice

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Geest, Rick van der, E-mail: r.van.der.geest@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands); Ouweneel, Amber B., E-mail: a.b.ouweneel@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands); Sluis, Ronald J. van der, E-mail: r.vandersluis@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands); Groen, Albert K., E-mail: a.k.groen@umcg.nl [University Medical Center Groningen (Netherlands); Van Eck, Miranda, E-mail: m.eck@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands); Hoekstra, Menno, E-mail: hoekstra@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands)

2016-09-01

Cholestatic liver disease is characterized by a disruption of bile flow, bile acid toxicity, liver injury, and hypercholesterolemia. Relatively high secretion of glucocorticoids by the adrenals has been observed under cholestatic conditions. Here we investigated a contribution of the rise in endogenous glucocorticoids to initial stage cholestasis pathology. Adrenalectomized or sham-operated control C57BL/6 mice were given an oral dose of alpha-naphthylisothiocyanate to induce cholestasis. Adrenalectomy effectively lowered plasma corticosterone levels (18 ± 5 ng/ml vs 472 ± 58 ng/ml; P < 0.001) and disrupted the metabolic and anti-inflammatory glucocorticoid function. Adrenal removal did not exacerbate the cholestasis extent. In contrast, the cholestasis-associated liver injury was markedly lower in adrenalectomized mice as compared to controls as evidenced by a 84%–93% decrease in liver necrosis and plasma alanine aminotransferase and bile acid levels (P < 0.001 for all). Gene expression analysis on livers from adrenalectomized mice suggested the absence of bile acid toxicity-associated farnesoid X receptor signaling in the context of a 44% (P < 0.01) and 82% (P < 0.001) reduction in sodium/bile acid cotransporter member 1 transcript level as compared to respectively control and non-diseased mice. Adrenalectomy reduced the expression of the cholesterol synthesis gene HMG-CoA reductase by 70% (P < 0.05), which translated into a 73% lower plasma total cholesterol level (P < 0.05). Treatment of C57BL/6 mice with the glucocorticoid receptor antagonist RU-486 recapitulated the protective effect of adrenalectomy on indices of liver injury and hypercholesterolemia. In conclusion, we have shown that endogenous glucocorticoids exacerbate the liver injury and hypercholesterolemia associated with acute cholestasis in mice. - Highlights: • Cholestasis is associated with increased plasma glucocorticoid levels in mice. • Adrenalectomy lowers cholestasis-associated liver

Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice.

Science.gov (United States)

Murach, Kevin A; White, Sarah H; Wen, Yuan; Ho, Angel; Dupont-Versteegden, Esther E; McCarthy, John J; Peterson, Charlotte A

2017-07-10

Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age. Pax7 CreER -R26R DTA mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age. Following a 2-week washout, mice were subjected to sham surgery or 10 day synergist ablation overload of the plantaris (n = 6-9 per group). The surgical approach minimized regeneration, de novo fiber formation, and fiber splitting while promoting muscle fiber growth. Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain expression (eMyHC), and muscle fiber cross sectional area (CSA) were evaluated via immunohistochemistry. Myonuclei (myonuclei/100 mm) were counted on isolated single muscle fibers. Tamoxifen treatment depleted satellite cells by ≥90% and prevented myonuclear accretion with overload in young and mature mice (p overload. Average muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p overload (p overload-induced hypertrophy is dependent on maturational age, and global responses to overload differ in young versus mature mice.

Evaluation of oxidative stress in mice subjected to aerobic exercise.

Science.gov (United States)

Lima, Mônica Cruvinel de; Marks, Guido; Silva, Iandara Schettert; Silva, Baldomero Antonio Kato da; Cônsolo, Lourdes Zélia Zanoni; Nogueira, Gabriel Bogalho

2012-08-01

To evaluate the influence of aerobic exercise on oxidative stress in mice. The study included twenty female mice Mus musculus-Swiss divided into two groups: sedentary control (GA) and exercise (GB), each containing ten animals. All animals underwent an adaptation period of seven days isolated in individual boxes. After this period, the animals in the exercise group (GB) were trained in angled running wheel with circumference of 25 cm assembled on an articulated axle during five minutes for three consecutive days. On the fourth day, they underwent an exercise program of one session lasting 45 minutes. The evaluation of oxidative stress was performed by determining the levels of malondialhyde derived of lipid peroxidation by the TBA method. The samples were read in a spectrophotometer at 535 nm. No significant difference was observed in the intergroup comparison of MDA levels in the tissues evaluated. A significant difference was observed in the intragroup comparison of MDA levels in the control group (p = 0.0201).The Tukeys' post hoc test indicated significantly lower values of MDA in the smooth muscle in relation to plasma. In the analysis of variance in the exercise group, a significant difference between tissues (p = 0.0009), with significantly lower values in the smooth muscle in relation to plasma (pstress in mice which were undergone a single session of aerobic exercise.

Effects of melatonin on spinal cord injury-induced oxidative damage in mice testis.

Science.gov (United States)

Yuan, X-C; Wang, P; Li, H-W; Wu, Q-B; Zhang, X-Y; Li, B-W; Xiu, R-J

2017-09-01

This study evaluated the effects of melatonin on spinal cord injury (SCI)-induced oxidative damage in testes. Adult male C57BL/6 mice were randomly divided into sham-, SCI- or melatonin (10 mg/kg, i.p.)-treated SCI groups. To induce SCI, a standard weight-drop method that induced a contusion injury at T10 was used. After 1 week, testicular blood flow velocity was measured using the Laser Doppler Line Scanner. Malondialdehyde (MDA), glutathione (GSH), oxidised glutathione (GSSG) and myeloperoxidase (MPO) were measured in testis homogenates. Microvascular permeability of the testes to Evan's Blue was examined by spectrophotometric and fluorescence microscopic quantitation. The tight junction protein zonula occludens-1 (ZO-1) and occludin in testes were assessed by immunoblot analysis. Melatonin increased the reduced blood flow and decreased SCI-induced permeability of capillaries. MDA levels and MPO activity were elevated in the SCI group compared with shams, which was reversed by melatonin. In contrast, SCI-induced reductions in GSH/GSSG ratio were restored by melatonin. Decreased expression of ZO-1 and occludin was observed, which was attenuated by melatonin. Overall, melatonin treatment protects the testes against oxidative stress damage caused by SCI. © 2016 Blackwell Verlag GmbH.

Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity.

Science.gov (United States)

Vieira Potter, Victoria J; Strissel, Katherine J; Xie, Chen; Chang, Eugene; Bennett, Grace; Defuria, Jason; Obin, Martin S; Greenberg, Andrew S

2012-09-01

Menopause promotes central obesity, adipose tissue (AT) inflammation, and insulin resistance (IR). Both obesity and the loss of estrogen can activate innate and adaptive immune cells (macrophages, T cells). The respective impacts of weight gain and loss of ovarian hormones on AT inflammation and IR are poorly understood. Here we determined the temporal kinetics of fat accretion, AT inflammation, and IR over a 26-wk time course in ovariectomized (OVX) mice, a model of menopause. OVX and sham-operated (SHM) C57BL6 mice were fed a normal chow diet. Weight, body composition (magnetic resonance imaging), total and regional adiposity, activity, food intake, AT crown-like structures, biohumoral measures, and insulin sensitivity (insulin tolerance testing and homeostatic model assessment) were determined at wk 12, 20, and 26. Macrophages and T cells from perigonadal AT were immunophenotyped by fluorescence-associated cell sorting, and perigonadal adipose tissue (PGAT) gene expression was quantified by quantitative PCR. OVX mice (≈ 31 g) became fatter than SHM mice (≈ 26 g) by wk 12, but mice were equally insulin sensitive. PGAT of OVX mice contained more T cells but expressed higher levels of M2-MΦ (arginase-1) and T cell-regulatory (cytotoxic T-lymphocyte antigen 4) genes. At wk 20, both OVX and SHM mice weighed approximately 35 g and were equally insulin sensitive with comparable amounts of PGAT and total body fat. OVX mice became less insulin sensitive than SHM mice by wk 26, coincident with the down-regulation of PGAT arginase-1 (-20-fold) and cytotoxic T-lymphocyte antigen 4 (2-fold) and up-regulation of M1/Th1 genes CD11c (+2-fold), IL12p40 (+2-fold), and interferon-γ (+78-fold). Ovarian hormone loss in mice induces PGAT inflammation and IR by mechanisms that can be uncoupled from OVX-induced obesity.

Brain immune cell composition and functional outcome after cerebral ischemia: Comparison of two mouse strains

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Hyun Ah eKim

2014-11-01

Full Text Available Inflammatory cells may contribute to secondary brain injury following cerebral ischemia. The C57Bl/6 mouse strain is known to exhibit a T helper 1-prone, pro-inflammatory type response to injury, whereas the FVB strain is relatively T helper 2-prone, or anti-inflammatory, in its immune response. We tested whether stroke outcome is more severe in C57Bl/6 than FVB mice. Male mice of each strain underwent sham surgery or 1 h occlusion of the middle cerebral artery followed by 23 h of reperfusion. Despite no difference in infarct size, C57Bl/6 mice displayed markedly greater functional deficits than FVB mice after stroke, as assessed by neurological scoring and hanging wire test. Total numbers of CD45+ leukocytes tended to be larger in the brains of C57Bl/6 than FVB mice after stroke, but there were marked differences in leukocyte composition between the two mouse strains. The inflammatory response in C57Bl/6 mice primarily involved T and B lymphocytes, whereas neutrophils, monocytes and macrophages were more prominent in FVB mice. Our data are consistent with the concept that functional outcome after stroke is dependent on the immune cell composition which develops following ischemic brain injury.

Global gene expression patterns in the post-pneumonectomy lung of adult mice

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Ingenito Edward P

2009-10-01

Full Text Available Abstract Background Adult mice have a remarkable capacity to regenerate functional alveoli following either lung resection or injury that exceeds the regenerative capacity observed in larger adult mammals. The molecular basis for this unique capability in mice is largely unknown. We examined the transcriptomic responses to single lung pneumonectomy in adult mice in order to elucidate prospective molecular signaling mechanisms used in this species during lung regeneration. Methods Unilateral left pneumonectomy or sham thoracotomy was performed under general anesthesia (n = 8 mice per group for each of the four time points. Total RNA was isolated from the remaining lung tissue at four time points post-surgery (6 hours, 1 day, 3 days, 7 days and analyzed using microarray technology. Results The observed transcriptomic patterns revealed mesenchymal cell signaling, including up-regulation of genes previously associated with activated fibroblasts (Tnfrsf12a, Tnc, Eln, Col3A1, as well as modulation of Igf1-mediated signaling. The data set also revealed early down-regulation of pro-inflammatory cytokine transcripts and up-regulation of genes involved in T cell development/function, but few similarities to transcriptomic patterns observed during embryonic or post-natal lung development. Immunohistochemical analysis suggests that early fibroblast but not myofibroblast proliferation is important during lung regeneration and may explain the preponderance of mesenchymal-associated genes that are over-expressed in this model. This again appears to differ from embryonic alveologenesis. Conclusion These data suggest that modulation of mesenchymal cell transcriptome patterns and proliferation of S100A4 positive mesenchymal cells, as well as modulation of pro-inflammatory transcriptome patterns, are important during post-pneumonectomy lung regeneration in adult mice.

From the Kohn-Sham band gap to the fundamental gap in solids. An integer electron approach

NARCIS (Netherlands)

Baerends, E. J.

2017-01-01

It is often stated that the Kohn-Sham occupied-unoccupied gap in both molecules and solids is "wrong". We argue that this is not a correct statement. The KS theory does not allow to interpret the exact KS HOMO-LUMO gap as the fundamental gap (difference (I - A) of electron affinity (A) and

A Kohn–Sham equation solver based on hexahedral finite elements

International Nuclear Information System (INIS)

Fang Jun; Gao Xingyu; Zhou Aihui

2012-01-01

We design a Kohn–Sham equation solver based on hexahedral finite element discretizations. The solver integrates three schemes proposed in this paper. The first scheme arranges one a priori locally-refined hexahedral mesh with appropriate multiresolution. The second one is a modified mass-lumping procedure which accelerates the diagonalization in the self-consistent field iteration. The third one is a finite element recovery method which enhances the eigenpair approximations with small extra work. We carry out numerical tests on each scheme to investigate the validity and efficiency, and then apply them to calculate the ground state total energies of nanosystems C 60 , C 120 , and C 275 H 172 . It is shown that our solver appears to be computationally attractive for finite element applications in electronic structure study.

Disruption of NBS1 gene leads to early embryonic lethality in homozygous null mice and induces specific cancer in heterozygous mice

Energy Technology Data Exchange (ETDEWEB)

Kurimasa, Akihiro; Burma, Sandeep; Henrie, Melinda; Ouyang, Honghai; Osaki, Mitsuhiko; Ito, Hisao; Nagasawa, Hatsumi; Little, John B.; Oshimura, Mitsuo; Li, Gloria C.; Chen, David J.

2002-04-15

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosome instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition, with cellular features similar to that of ataxia telangiectasia (AT). NBS results from mutations in the mammalian gene Nbs1 that codes for a 95-kDa protein called nibrin, NBS1, or p95. To establish an animal model for NBS, we attempted to generate NBS1 knockout mice. However, NBS1 gene knockouts were lethal at an early embryonic stage. NBS1 homozygous(-/-) blastocyst cells cultured in vitro showed retarded growth and subsequently underwent growth arrest within 5 days of culture. Apoptosis, assayed by TUNEL staining, was observed in NBSI homozygous(-/-) blastocyst cells cultured for four days. NBSI heterozygous(+/-) mice were normal, and exhibited no specific phenotype for at least one year. However, fibroblast cells from NBSI heterozygous(+/-) mice displayed an enhanced frequency of spontaneous transformation to anchorage-independent growth as compared to NBS1 wild-type(+/+) cells. Furthermore, heterozygous(+/-) mice exhibited a high incidence of hepatocellular carcinoma after one year compared to wild-type mice, even though no significant differences in the incidence of other tumors such as lung adenocarcinoma and lymphoma were observed. Taken together, these results strongly suggest that NBS1 heterozygosity and reduced NBSI expression induces formation of specific tumors in mice.

Acupuncture at Waiguan (SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study.

Science.gov (United States)

Qi, Ji; Chen, Junqi; Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Chen, Hua; Qu, Shanshan

2014-02-01

Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group (true acupuncture at right Waiguan (SJ5)) and sham point group (sham acupuncture). Results of functional magnetic resonance imaging revealed activation in right parietal lobe (Brodmann areas 7 and 19), the right temporal lobe (Brodmann area 39), the right limbic lobe (Brodmann area 23) and bilateral occipital lobes (Brodmann area 18). Furthermore, inhibition of bilateral frontal lobes (Brodmann area 4, 6, and 45), right parietal lobe (Brodmann areas 1 and 5) and left temporal lobe (Brodmann area 21) were observed in the true point group. Activation in the precuneus of right parietal lobe (Brodmann area 7) and inhibition of the left superior frontal gyrus (Brodmann area 10) was observed in the sham group. Compared with sham acupuncture, acupuncture at Waiguan in stroke patients inhibited Brodmann area 5 on the healthy side. Results indicated that the altered specificity of sensation-associated cortex (Brodmann area 5) is possibly associated with a central mechanism of acupuncture at Waiguan for stroke patients.

Protective effects of oridonin on the sepsis in mice

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Yan-Jun Zhao

2016-09-01

Full Text Available This study aimed to investigate the protective effects of oridonin (ORI on cecal ligation and puncture (CLP-induced sepsis in mice. Male C57BL/6 mice weighing 22–30 g and aged 8–10 weeks were randomly assigned to three groups: Sham group, CLP group, or CLP plus ORI group. In the CLP group and ORI group, CLP was induced, and intraperitoneal injection of normal saline and oridonin (100 μg/kg was conducted, respectively. The survival rate was determined within the following 7 days. The blood, liver, and lung were collected at 24 hours after injury. Hematoxylin–eosin staining of the lung, detection of lung wet-to-dry ratio, and serum cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6, and examination of intraperitoneal and blood bacterial clearance were conducted to evaluate the therapeutic efficacy. Results showed that ORI treatment significantly reduced the lung wet-to-dry ratio, decreased serum TNF-α and IL-6, and improved liver pathology compared with the CLP group (p < 0.05. Moreover, the intraperitoneal and blood bacterial clearance increased markedly after ORI treatment (p < 0.05. The 7-day survival rate in the ORI group was also dramatically higher than in the CLP group (p < 0.05. Our findings indicate that ORI can attenuate liver and lung injuries and elevate bacterial clearance to increase the survival rate of sepsis mice.

Hyperexpressed netrin-1promoted neural stem cells migration in mice after focal cerebral ischemia

OpenAIRE

Haiyan Lu; Xiaoyan Song; Feng Wang; Guodong Wang; Yuncheng Wu; Qiaoshu Wang; Yongting Wang; Guoyuan Yang; Zhijun Zhang

2016-01-01

Endogenous Netrin-1 (NT-1) protein was significantly increased after cerebral ischemia, which may participate in the repair after transient cerebral ischemic injury. In this work, we explored whether NT-1 can be steadily overexpressed by adeno-associated virus (AAV) and the exogenous NT-1 can promote neural stem cells migration from the subventricular zone (SVZ) region after cerebral ischemia. Adult CD-1 mice were injected stereotacticly with AAV carrying NT-1 gene (AAV-NT-1). Mice underwent ...

Acupuncture at Waiguan (SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study

OpenAIRE

Qi, Ji; Chen, Junqi; Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Chen, Hua; Qu, Shanshan

2014-01-01

Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group (true acupuncture at right Waiguan (SJ5)) and sham point group (sham acupuncture). Results of functional magnetic resonance imaging revea...

Inhibition of the soluble epoxide hydrolase promotes albuminuria in mice with progressive renal disease.

Directory of Open Access Journals (Sweden)

Oliver Jung

2010-08-01

Full Text Available Epoxyeicotrienoic acids (EETs are cytochrome P450-dependent anti-hypertensive and anti-inflammatory derivatives of arachidonic acid, which are highly abundant in the kidney and considered reno-protective. EETs are degraded by the enzyme soluble epoxide hydrolase (sEH and sEH inhibitors are considered treatment for chronic renal failure (CRF. We determined whether sEH inhibition attenuates the progression of CRF in the 5/6-nephrectomy model (5/6-Nx in mice. 5/6-Nx mice were treated with a placebo, an ACE-inhibitor (Ramipril, 40 mg/kg, the sEH-inhibitor cAUCB or the CYP-inhibitor fenbendazole for 8 weeks. 5/6-Nx induced hypertension, albuminuria, glomerulosclerosis and tubulo-interstitial damage and these effects were attenuated by Ramipril. In contrast, cAUCB failed to lower the blood pressure and albuminuria was more severe as compared to placebo. Plasma EET-levels were doubled in 5/6 Nx-mice as compared to sham mice receiving placebo. Renal sEH expression was attenuated in 5/6-Nx mice but cAUCB in these animals still further increased the EET-level. cAUCB also increased 5-HETE and 15-HETE, which derive from peroxidation or lipoxygenases. Similar to cAUCB, CYP450 inhibition increased HETEs and promoted albuminuria. Thus, sEH-inhibition failed to elicit protective effects in the 5/6-Nx model and showed a tendency to aggravate the disease. These effects might be consequence of a shift of arachidonic acid metabolism into the lipoxygenase pathway.

A recombinant bivalent fusion protein rVE confers active and passive protection against Yersinia enterocolitica infection in mice.

Science.gov (United States)

Singh, Amit Kumar; Kingston, Joseph Jeyabalaji; Murali, Harishchandra Sripathy; Batra, Harsh Vardhan

2014-03-05

In the present study, a bivalent chimeric protein rVE comprising immunologically active domains of Yersinia pestis LcrV and YopE was assessed for its prophylactic abilities against Yersinia enterocolitica O:8 infection in murine model. Mice immunized with rVE elicited significantly higher antibody titers with substantial contribution from the rV component (3:1 ratio). Robust and significant resistance to Y. enterocolitica infection with 100% survival (Penterocolitica O:8 against the 75%, 60% and 75% survival seen in mice immunized with rV, rE, rV+rE, respectively. Macrophage monolayer supplemented with anti-rVE polysera illustrated efficient protection (89.41% survival) against challenge of Y. enterocolitica O:8. In contrast to sera from sham-immunized mice, immunization with anti-rVE polysera provided complete protection to BALB/c mice against I.P. challenge with 10(8)CFU of Y. enterocolitica O:8 and developed no conspicuous signs of infection in necropsy. The histopathological analysis of microtome sections confirmed significantly reduced lesion size or no lesion in liver and intestine upon infection in anti-rVE immunized mice. The findings from this study demonstrated the fusion protein rVE as a potential candidate subunit vaccine and showed the functional role of antibodies in protection against Y. enterocolitica infections. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reduced brain-derived neurotrophic factor expression in cortex and hippocampus involved in the learning and memory deficit in molarless SAMP8 mice

Institute of Scientific and Technical Information of China (English)

JIANG Qing-song; LIANG Zi-liang; WU Min-Jie; FENG Lin; LIU Li-li; ZHANG Jian-jun

2011-01-01

Background The molarless condition has been reported to compromise learning and memory functions. However, it remains unclear how the molarless condition directly affects the central nervous system, and the functional consequences on the brain cortex and hippocampus have not been described in detail. The aim of this study was to find the molecular mechanism related with learning and memory deficit after a bilateral molarless condition having been surgically induced in senescence-accelerated mice/prone8 (SAMP8) mice, which may ultimately provide an experimental basis for clinical prevention of senile dementia.Methods Mice were either sham-operated or subjected to complete molar removal. The animals' body weights were monitored every day. Learning ability and memory were measured in a water maze test at the end of the 1 st, 2nd, and 3rd months after surgery. As soon as significantly prolonged escape latency in the molarless group was detected, the locomotor activity was examined in an open field test. Subsequently, the animals were decapitated and the cortex and hippocampus were dissected for Western blotting to measure the expression levels of brain-derived neurotrophic factor (BDNF) and the tropomyosin related kinase B (TrkB), the high affinity receptor of BDNF.Results Slightly lower weights were consistently observed in the molarless group, but there was no significant difference in weights between the two groups (P＞0.05). Compared with the sham group, the molarless group exhibited lengthened escape latency in the water maze test three months after surgery, whereas no difference in locomotor activity was observed. Meanwhile, in the cortex and hippocampus, BDNF levels were significantly decreased in the molarless group (P＜0.05); but the expression of its receptor, TrkB, was not significantly affected.Conclusion These results suggested that the molarless condition impaired learning and memory abilities in SAMP8mice three months after teeth extraction, and this

Improved healing response in delayed unions of the tibia with low-intensity pulsed ultrasound: results of a randomized sham-controlled trial

Directory of Open Access Journals (Sweden)

Aigner Julia

2010-10-01

Full Text Available Abstract Background We compared the healing response of tibial delayed unions between subjects treated with low-intensity pulsed ultrasound (LIPUS (n = 51 and subjects treated with a sham device (n = 50. Fracture age was ≥ 4 months in all cases. Study personnel and participants were blinded to random treatment assignment throughout the study. Methods This multi-center randomized sham-controlled trial was undertaken at six hospitals in Germany. Adult patients who had sustained a tibial shaft fracture that subsequently showed inadequate progress toward healing (i.e., delayed union were enrolled and randomized to receive either LIPUS (Exogen 2000/2000+, Smith & Nephew GmbH, Schenefeld, Germany or an identical nonoperative sham device. The daily treatment duration was 20 minutes, for a period of 16 weeks. Subjects randomly assigned to active treatment had the ultrasound pressure wave signal set at the following parameters: 1.5 MHz frequency, 1 kHz repetition rate, 200 μs pulse duration, 30 mW/cm2 spatial intensity. Progress toward healing was estimated from changes in bone mineral density (BMD and gap area as determined from computed tomography scans. Intention-to-treat analysis was conducted using a multiple imputation methodology. Results Based on log-transformed data, mean improvement in BMD was 1.34 (90% confidence interval (CI 1.14 to 1.57 times greater for LIPUS-treated subjects compared to sham (p = 0.002. A mean reduction in bone gap area also favored LIPUS treatment (p = 0.014. Conclusions These findings demonstrate significantly greater progress toward bone healing after LIPUS treatment compared to no LIPUS treatment in subjects with established delayed unions of the tibia.

Stability conditions for exact-exchange Kohn-Sham methods and their relation to correlation energies from the adiabatic-connection fluctuation-dissipation theorem.

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Bleiziffer, Patrick; Schmidtel, Daniel; Görling, Andreas

2014-11-28

The occurrence of instabilities, in particular singlet-triplet and singlet-singlet instabilities, in the exact-exchange (EXX) Kohn-Sham method is investigated. Hessian matrices of the EXX electronic energy with respect to the expansion coefficients of the EXX effective Kohn-Sham potential in an auxiliary basis set are derived. The eigenvalues of these Hessian matrices determine whether or not instabilities are present. Similar as in the corresponding Hartree-Fock case instabilities in the EXX method are related to symmetry breaking of the Hamiltonian operator for the EXX orbitals. In the EXX methods symmetry breaking can easily be visualized by displaying the local multiplicative exchange potential. Examples (N2, O2, and the polyyne C10H2) for instabilities and symmetry breaking are discussed. The relation of the stability conditions for EXX methods to approaches calculating the Kohn-Sham correlation energy via the adiabatic-connection fluctuation-dissipation (ACFD) theorem is discussed. The existence or nonexistence of singlet-singlet instabilities in an EXX calculation is shown to indicate whether or not the frequency-integration in the evaluation of the correlation energy is singular in the EXX-ACFD method. This method calculates the Kohn-Sham correlation energy through the ACFD theorem theorem employing besides the Coulomb kernel also the full frequency-dependent exchange kernel and yields highly accurate electronic energies. For the case of singular frequency-integrands in the EXX-ACFD method a regularization is suggested. Finally, we present examples of molecular systems for which the self-consistent field procedure of the EXX as well as the Hartree-Fock method can converge to more than one local minimum depending on the initial conditions.

Stability conditions for exact-exchange Kohn-Sham methods and their relation to correlation energies from the adiabatic-connection fluctuation-dissipation theorem

International Nuclear Information System (INIS)

Bleiziffer, Patrick; Schmidtel, Daniel; Görling, Andreas

2014-01-01

The occurrence of instabilities, in particular singlet-triplet and singlet-singlet instabilities, in the exact-exchange (EXX) Kohn-Sham method is investigated. Hessian matrices of the EXX electronic energy with respect to the expansion coefficients of the EXX effective Kohn-Sham potential in an auxiliary basis set are derived. The eigenvalues of these Hessian matrices determine whether or not instabilities are present. Similar as in the corresponding Hartree-Fock case instabilities in the EXX method are related to symmetry breaking of the Hamiltonian operator for the EXX orbitals. In the EXX methods symmetry breaking can easily be visualized by displaying the local multiplicative exchange potential. Examples (N 2 , O 2 , and the polyyne C 10 H 2 ) for instabilities and symmetry breaking are discussed. The relation of the stability conditions for EXX methods to approaches calculating the Kohn-Sham correlation energy via the adiabatic-connection fluctuation-dissipation (ACFD) theorem is discussed. The existence or nonexistence of singlet-singlet instabilities in an EXX calculation is shown to indicate whether or not the frequency-integration in the evaluation of the correlation energy is singular in the EXX-ACFD method. This method calculates the Kohn-Sham correlation energy through the ACFD theorem theorem employing besides the Coulomb kernel also the full frequency-dependent exchange kernel and yields highly accurate electronic energies. For the case of singular frequency-integrands in the EXX-ACFD method a regularization is suggested. Finally, we present examples of molecular systems for which the self-consistent field procedure of the EXX as well as the Hartree-Fock method can converge to more than one local minimum depending on the initial conditions

Clinical Evaluation of Acupuncture as Treatment for Complications of Cerebrovascular Accidents: A Randomized, Sham-Controlled, Subject- and Assessor-Blind Trial.

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Liao, Hsien-Yin; Ho, Wen-Chao; Chen, Chun-Chung; Lin, Jaung-Geng; Chang, Chia-Chi; Chen, Liang-Yu; Lee, De-Chih; Lee, Yu-Chen

2017-01-01

Background and Purpose . The effect of acupuncture as treatment for poststroke complications is questionable. We performed a randomized, sham-controlled double-blind study to investigate it. Methods . Patients with first-time acute stroke were randomized to receive 24 sessions of either real or sham acupuncture during an eight-week period. The primary outcome measure was change in National Institute of Health Stroke Scale (NIHSS) score. Secondary outcome measures included changes in Barthel Index (BI), Instrumental Activities of Daily Living (IADL), Hamilton Depression Rating Scale (HAM-D), and Visual Analogue Scale (VAS) for pain scores. Results . Of the 52 patients who were randomized to receive acupuncture ( n = 28) or placebo ( n = 24), 10 patients in the acupuncture group and 9 patients in the placebo group failed to complete the treatment. In total, 18 patients in the acupuncture group and 15 patients in the control group completed the treatment course. Reduction in pain was significantly greater in the acupuncture group than in the control group ( p value = 0.04). There were no significant differences in the other measures between the two groups. Conclusions . Acupuncture provided more effective poststroke pain relief than sham acupuncture treatment. However, acupuncture had no better effect on neurological, functional, and psychological improvement.

A self-interaction-free local hybrid functional: Accurate binding energies vis-à-vis accurate ionization potentials from Kohn-Sham eigenvalues

International Nuclear Information System (INIS)

Schmidt, Tobias; Kümmel, Stephan; Kraisler, Eli; Makmal, Adi; Kronik, Leeor

2014-01-01

We present and test a new approximation for the exchange-correlation (xc) energy of Kohn-Sham density functional theory. It combines exact exchange with a compatible non-local correlation functional. The functional is by construction free of one-electron self-interaction, respects constraints derived from uniform coordinate scaling, and has the correct asymptotic behavior of the xc energy density. It contains one parameter that is not determined ab initio. We investigate whether it is possible to construct a functional that yields accurate binding energies and affords other advantages, specifically Kohn-Sham eigenvalues that reliably reflect ionization potentials. Tests for a set of atoms and small molecules show that within our local-hybrid form accurate binding energies can be achieved by proper optimization of the free parameter in our functional, along with an improvement in dissociation energy curves and in Kohn-Sham eigenvalues. However, the correspondence of the latter to experimental ionization potentials is not yet satisfactory, and if we choose to optimize their prediction, a rather different value of the functional's parameter is obtained. We put this finding in a larger context by discussing similar observations for other functionals and possible directions for further functional development that our findings suggest

Clinical Evaluation of Acupuncture as Treatment for Complications of Cerebrovascular Accidents: A Randomized, Sham-Controlled, Subject- and Assessor-Blind Trial

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Hsien-Yin Liao

2017-01-01

Full Text Available Background and Purpose. The effect of acupuncture as treatment for poststroke complications is questionable. We performed a randomized, sham-controlled double-blind study to investigate it. Methods. Patients with first-time acute stroke were randomized to receive 24 sessions of either real or sham acupuncture during an eight-week period. The primary outcome measure was change in National Institute of Health Stroke Scale (NIHSS score. Secondary outcome measures included changes in Barthel Index (BI, Instrumental Activities of Daily Living (IADL, Hamilton Depression Rating Scale (HAM-D, and Visual Analogue Scale (VAS for pain scores. Results. Of the 52 patients who were randomized to receive acupuncture (n=28 or placebo (n=24, 10 patients in the acupuncture group and 9 patients in the placebo group failed to complete the treatment. In total, 18 patients in the acupuncture group and 15 patients in the control group completed the treatment course. Reduction in pain was significantly greater in the acupuncture group than in the control group (p value = 0.04. There were no significant differences in the other measures between the two groups. Conclusions. Acupuncture provided more effective poststroke pain relief than sham acupuncture treatment. However, acupuncture had no better effect on neurological, functional, and psychological improvement.

[Facilitation of the retention and acceleration of operant conditioning extinction after cingulate cortex lesions in BALB/c mice].

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Destrade, C; Gauthier, M

1981-12-21

One week after receiving bilateral electrolytic lesions of the cingulate cortex, BALB/c Mice underwent acquisition, retention and extinction of an appetitive operant-conditioning task in a Skinner box. There was no significant difference between lesioned and control animals in acquisition; however, lesioned mice exhibited improved retention and faster extinction. These results suggest a possible involvement of the cingulate cortex in memory processes.

Inhibition of 2-arachydonoylgycerol degradation attenuates orofacial neuropathic pain in trigeminal nerve-injured mice.

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Kamimura, Rantaro; Hossain, Mohammad Z; Unno, Shumpei; Ando, Hiroshi; Masuda, Yuji; Takahashi, Kojiro; Otake, Masanori; Saito, Isao; Kitagawa, Junichi

2018-03-24

Current therapeutics are not effective for orofacial neuropathic pain, and better options are needed. The present study used inferior orbital nerve (ION)-injured mice to investigate the effect of inhibiting monoacylglycerol lipase (MAGL), an enzyme that degrades the major endocannabinoid 2-arachydonoylgycerol (2-AG) in orofacial neuropathic pain. The head-withdrawal threshold to mechanical stimulation of the whisker pad was reduced on days 3, 5, and 7 after ION injury. Injection of JZL184, a selective inhibitor of MAGL, on day 7 after ION injury attenuated the reduction in head-withdrawal threshold at 2 h after administration. Moreover, the numbers of MAGL-immunoreactive neurons in the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were significantly greater in ION-injured mice than in sham-operated mice but were reduced after administration of JZL184. The increase in MAGL immunoreactivity suggests that increased 2-AG production is followed by rapid enzymatic degradation of 2-AG. JZL184 inhibited this degradation and thus increased 2-AG concentration in the brain, particularly in the Vc and C1-C2 regions, thus attenuating pain. Our findings suggest that inhibition of 2-AG degradation by MAGL inhibitors is a promising therapeutic option for treatment of orofacial neuropathic pain.

A Randomized, Double-Blind, Sham-Controlled Trial of Transcranial Direct Current Stimulation in Attention-Deficit/Hyperactivity Disorder.

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Camila Cosmo

Full Text Available Current standardized treatments for cognitive impairment in attention-deficit/hyperactivity disorder remain limited and their efficacy restricted. Transcranial direct current stimulation (tDCS is a promising tool for enhancing cognitive performance in several neuropsychiatric disorders. Nevertheless, the effects of tDCS in reducing cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD have not yet been investigated.A parallel, randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on the modulation of inhibitory control in adults with ADHD. Thirty patients were randomly allocated to each group and performed a go/no-go task before and after a single session of either anodal stimulation (1 mA over the left dorsolateral prefrontal cortex or sham stimulation.A nonparametric two-sample Wilcoxon rank-sum (Mann-Whitney test revealed no significant differences between the two groups of individuals with ADHD (tDCS vs. sham in regard to behavioral performance in the go/no go tasks. Furthermore, the effect sizes of group differences after treatment for the primary outcome measures-correct responses, impulsivity and omission errors--were small. No adverse events resulting from stimulation were reported.According to these findings, there is no evidence in support of the use of anodal stimulation over the left dorsolateral prefrontal cortex as an approach for improving inhibitory control in ADHD patients. To the best of our knowledge, this is the first clinical study to assess the cognitive effects of tDCS in individuals with ADHD. Further research is needed to assess the clinical efficacy of tDCS in this population.ClinicalTrials.gov NCT01968512.

The carcinogenic effects of fetal and postnatal radiation in female mice

International Nuclear Information System (INIS)

Kusama, Tomoko; Yoshizawa, Yasuo

1982-01-01

The present study was designed to investigate the carcinogenic effects of fetal and postnatal irradiation in female mice. The C57BL/6J mice were subjected to whole-body exposure to 1-Gy or 4-Gy 137 Cs γ-ray irradiation on the 15th fetal day or the 30th postnatal day. Following this, all mice were observed throughout their respective life spans under conventional rearing conditions. The tumor incidence rate, average latent period and distributions of various tumors were used as the quantitative parameters of radiation-induced carcinogenesis. The following conclusions can be draw: (1) The mean life span of mice that underwent 4-Gy irradiation at the age of 30 days was shorter than that of non-irradiated control mice. (2) In control mice, the tumor incidence was 75.7%. (3) In order to estimate the mean age and tumor incidence, an adjustment for competing death is necessary. (4) The adjusted tumor incidences of thymic lymphoma and breast tumor of the irradiated groups were not different from those of control group. On the other hand, there was a significant difference between the two in the adjusted incidence of reticular tissue neoplasm. (author)

Independent effects of sham laparotomy and anesthesia on hepatic microRNA expression in rats.

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Werner, Wiebke; Sallmon, Hannes; Leder, Annekatrin; Lippert, Steffen; Reutzel-Selke, Anja; Morgül, Mehmet Haluk; Jonas, Sven; Dame, Christof; Neuhaus, Peter; Iacomini, John; Tullius, Stefan G; Sauer, Igor M; Raschzok, Nathanael

2014-10-08

Studies on liver regeneration following partial hepatectomy (PH) have identified several microRNAs (miRNAs) that show a regulated expression pattern. These studies involve major surgery to access the liver, which is known to have intrinsic effects on hepatic gene expression and may also affect miRNA screening results. We performed two-third PH or sham laparotomy (SL) in Wistar rats to investigate the effect of both procedures on miRNA expression in liver tissue and corresponding plasma samples by microarray and qRT-PCR analyses. As control groups, non-treated rats and rats undergoing anesthesia only were used. We found that 49 out of 323 miRNAs (15%) were significantly deregulated after PH in liver tissue 12 to 48 hours postoperatively (>20% change), while 45 miRNAs (14%) were deregulated following SL. Out of these miRNAs, 10 miRNAs were similarly deregulated after PH and SL, while one miRNA showed opposite regulation. In plasma, miRNA upregulation was observed for miR-133a and miR-133b following PH and SL, whereas miR-100 and miR-466c were similarly downregulated following anesthesia and surgery. We show that miRNAs are indeed regulated by sham laparotomy and anesthesia in rats. These findings illustrate the critical need for finding appropriate control groups in experimental surgery.

Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice.

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Dieguez, Hernán H; Romeo, Horacio E; González Fleitas, María F; Aranda, Marcos L; Milne, Georgia A; Rosenstein, Ruth E; Dorfman, Damián

2018-02-07

Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy) on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and

Functional renormalization group and Kohn-Sham scheme in density functional theory

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Liang, Haozhao; Niu, Yifei; Hatsuda, Tetsuo

2018-04-01

Deriving accurate energy density functional is one of the central problems in condensed matter physics, nuclear physics, and quantum chemistry. We propose a novel method to deduce the energy density functional by combining the idea of the functional renormalization group and the Kohn-Sham scheme in density functional theory. The key idea is to solve the renormalization group flow for the effective action decomposed into the mean-field part and the correlation part. Also, we propose a simple practical method to quantify the uncertainty associated with the truncation of the correlation part. By taking the φ4 theory in zero dimension as a benchmark, we demonstrate that our method shows extremely fast convergence to the exact result even for the highly strong coupling regime.

Lack of macrophage migration inhibitory factor in mice does not affect hallmarks of the inflammatory/immune response during the first week after stroke

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Deierborg Tomas

2011-06-01

Full Text Available Abstract Background Macrophage migration inhibitory factor (MIF has been proposed to play a detrimental role in stroke. We recently showed that MIF promotes neuronal death and aggravates neurological deficits during the first week after experimental stroke, in mice. Since MIF regulates tissue inflammation, we studied the putative role of MIF in post-stroke inflammation. Methods We subjected C57BL/6 mice, Mif-/- (MIF-KO or Mif+/+ (WT, to a transient occlusion of the right middle cerebral artery (tMCAo or sham-surgery. We studied MIF expression, GFAP expression and the number of CD74-positive cells in the ischemic brain hemisphere 7 days after tMCAo using primarily immunohistochemistry. We determined IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-12, KC/CXCL-1 and TNF-α protein levels in the brain (48 h after surgery and serum (48 h and 7 days after surgery by a multiplex immunoassay. Results We observed that MIF accumulates in neurons and astrocytes of the peri-infarct region, as well as in microglia/macrophages of the infarct core up to 7 days after stroke. Among the inflammatory mediators analyzed, we found a significant increase in cerebral IL-12 and KC levels after tMCAo, in comparison to sham-surgery. Importantly, the deletion of Mif did not significantly affect the levels of the cytokines evaluated, in the brain or serum. Moreover, the spleen weight 48 h and 7 days subsequent to tMCAo was similar in WT and MIF-KO mice. Finally, the extent of GFAP immunoreactivity and the number of MIF receptor (CD74-positive cells within the ischemic brain hemisphere did not differ significantly between WT and MIF-KO mice subjected to tMCAo. Conclusions We conclude that MIF does not affect major components of the inflammatory/immune response during the first week after experimental stroke. Based on present and previous evidence, we propose that the deleterious MIF-mediated effects in stroke depend primarily on an intraneuronal and/or interneuronal action.

Netrin-1 overexpression promotes white matter repairing and remodeling after focal cerebral ischemia in mice

OpenAIRE

He, Xiaosong; Li, Yaning; Lu, Haiyan; Zhang, Zhijun; Wang, Yongting; Yang, Guo-Yuan

2013-01-01

Damage of oligodendrocytes after ischemia has negative impact on white matter integrity and neuronal function. In this work, we explore whether Netrin-1 (NT-1) overexpression facilitates white matter repairing and remodeling. Adult CD-1 mice received stereotactic injection of adeno-associated virus carrying NT-1 gene (AAV-NT-1). One week after gene transfer, mice underwent 60 minutes of middle cerebral artery occlusion. The effect of NT-1 on neural function was evaluated by neurobehavioral te...

Chronic exercise prevents repeated restraint stress-provoked enhancement of immobility in forced swimming test in ovariectomized mice.

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Han, Tae-Kyung; Lee, Jang-Kyu; Leem, Yea-Hyun

2015-06-01

We assessed whether chronic treadmill exercise attenuated the depressive phenotype induced by restraint stress in ovariectomized mice (OVX). Immobility of OVX in the forced swimming test was comparable to that of sham mice (CON) regardless of the postoperative time. Immobility was also no difference between restrained mice (exposure to periodic restraint for 21 days; RST) and control mice (CON) on post-exposure 2nd and 9th day, but not 15th day. In contrast, the immobility of ovariectomized mice with repeated stress (OVX + RST) was profoundly enhanced compared to ovariectomized mice-alone (OVX), and this effect was reversed by chronic exercise (19 m/min, 60 min/day, 5 days/week for 8 weeks; OVX + RST + Ex) or fluoxetine administration (20 mg/kg, OVX + RST + Flu). In parallel with behavioral data, the immunoreactivity of Ki-67 and doublecortin (DCX) in OVX was significantly decreased by repeated stress. However, the reduced numbers of Ki-67- and DCX-positive cells in OVX + RST were restored in response to chronic exercise (OVX + RST + Ex) and fluoxetine (OVX + RST + Flu). In addition, the expression pattern of cAMP response element-binding protein (CREB) and calcium-calmodulin-dependent kinase IV (CaMKIV) was similar to that of the hippocampal proliferation and neurogenesis markers (Ki-67 and DCX, respectively). These results suggest that menopausal depression may be induced by an interaction between repeated stress and low hormone levels, rather than a deficit in ovarian secretion alone, which can be improved by chronic exercise.

Combined effects of soy isoflavone and fish oil on ovariectomy-induced bone loss in mice.

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Uchida, Raina; Chiba, Hiroshige; Ishimi, Yoshiko; Uehara, Mariko; Suzuki, Kazuharu; Kim, Hyounju; Matsumoto, Akiyo

2011-07-01

Both soy isoflavone and n-3 polyunsaturated fatty acids are known to reduce the levels of bone-resorbing cytokines; however, the synergistic effects of these food ingredients have not been examined yet. This study was performed to elucidate the effect of concomitant intake of soy isoflavone and fish oil on bone mass in ovariectomized mice. Eight-week-old ddY female mice were subjected to ovariectomy (OVX) or sham surgery, and then fed an AIN-93G with safflower oil (So) as a control lipid source, isoflavone-supplemented safflower oil (So + I), fish oil instead of safflower oil (Fo) or isoflavone-supplemented fish oil (Fo + I) for 4 weeks. Femoral bone mineral density was significantly decreased by OVX; however, this decrease was inhibited by the intake of isoflavone and/or fish oil. Histomorphometric analyses showed that bone volume and trabecular thickness in the distal femoral trabecular bone were significantly lower in the So group than in the sham group, but those were restored in the Fo + I groups. The number of osteoclasts was significantly decreased by isoflavone intake. The increased rate of bone resorption after OVX was inhibited by isoflavone and/or fish oil. The serum concentration of tumor necrosis factor alpha was increased after OVX, but was significantly lower with the combination of isoflavone with fish oil than isoflavone or fish oil alone. The results of this study indicated that the intakes of soy isoflavone and/or fish oil might have ameliorating effects on bone loss due to OVX. Further, the concomitant intake of soy isoflavone and fish oil at a low dose showed better effects on cytokines related with bone resorption.

Uncoupling protein-2 mRNA expression in mice subjected to intermittent hypoxia

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Luciana Rodrigues Vieira

2015-04-01

Full Text Available Objective: To investigate the effect of intermittent hypoxia-a model of obstructive sleep apnea (OSA-on pancreatic expression of uncoupling protein-2 (UCP2, as well as on glycemic and lipid profiles, in C57BL mice. Methods: For 8 h/day over a 35-day period, male C57BL mice were exposed to intermittent hypoxia (hypoxia group or to a sham procedure (normoxia group. The intermittent hypoxia condition involved exposing mice to an atmosphere of 92% N and 8% CO2 for 30 s, progressively reducing the fraction of inspired oxygen to 8 ± 1%, after which they were exposed to room air for 30 s and the cycle was repeated (480 cycles over the 8-h experimental period. Pancreases were dissected to isolate the islets. Real-time PCR was performed with TaqMan assays. Results: Expression of UCP2 mRNA in pancreatic islets was 20% higher in the normoxia group than in the hypoxia group (p = 0.11. Fasting serum insulin was higher in the hypoxia group than in the normoxia group (p = 0.01. The homeostasis model assessment of insulin resistance indicated that, in comparison with the control mice, the mice exposed to intermittent hypoxia showed 15% lower insulin resistance (p = 0.09 and 21% higher pancreatic β-cell function (p = 0.01. Immunohistochemical staining of the islets showed no significant differences between the two groups in terms of the area or intensity of α- and β-cell staining for insulin and glucagon. Conclusions: To our knowledge, this is the first report of the effect of intermittent hypoxia on UCP2 expression. Our findings suggest that UCP2 regulates insulin production in OSA. Further study of the role that UCP2 plays in the glycemic control of OSA patients is warranted.

Divergent systemic and local inflammatory response to hind limb demand ischemia in wild-type and ApoE-/- mice.

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Crawford, Robert S; Albadawi, Hassan; Robaldo, Alessandro; Peck, Michael A; Abularrage, Christopher J; Yoo, Hyung-Jin; Lamuraglia, Glenn M; Watkins, Michael T

2013-08-01

We designed studies to determine whether the ApoE-/- phenotype modulates the local skeletal muscle and systemic inflammatory (plasma) responses to lower extremity demand ischemia. The ApoE-/- phenotype is an experimental model for atherosclerosis in humans. Aged female ApoE-/- and C57BL6 mice underwent femoral artery ligation, then were divided into sedentary and demand ischemia (exercise) groups on day 14. We assessed baseline and postexercise limb perfusion and hind limb function. On day 14, animals in the demand ischemia group underwent daily treadmill exercise through day 28. Sedentary mice were not exercised. On day 28, we harvested plasma and skeletal muscle from ischemic limbs from sedentary and exercised mice. We assayed muscle for angiogenic and proinflammatory proteins, markers of skeletal muscle regeneration, and evidence of skeletal muscle fiber maturation. Hind limb ischemia was similar in ApoE-/- and C57 mice before the onset of exercise. Under sedentary conditions, plasma vascular endothelial cell growth factor and interleukin-6, but not keratinocyte chemoattractant factor (KC) or macrophage inflammatory protein-2 (MIP-2), were higher in ApoE (P factor, KC, and MIP-2, but not IL-6, were lower in ApoE (P demand ischemia in the C57BL6 mice, compared with the ApoE-/- mice (P = 0.01). Demand limb ischemia in the ApoE-/- phenotype exacerbated the expression of select systemic cytokines in plasma and blunted indices of muscle regeneration. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of radiation in chemical leukemogenesis in mice

International Nuclear Information System (INIS)

Kajitani, Takashi; Hamada, Katsutomo; Ito, Takaaki; Yokoro, Kenjiro

1980-01-01

Leukemia was induced in adult mice 6 to 8 months of age by the combined use of x-rays and N-nitrosoethylurea (NEU). Changes in thymocytes due to irradiation with x-rays were studied in order to determine the mechanism of leukemogenesis. The incidence of leukemia was 61.3% in mice given sucessive doses of NEU immediately after whole-body irradiation with x-rays and 18.8% in mice given successive doses of NEU 3 months after whole-body irradiation with x-rays. The thymus weight, the thymocyte count, the mitotic index in thymocytes, and the rate of DNA-synthesizing cells in the thymus decreased rapidly in both adult and young adult mice that underwent whole-body irradiation (400 R). The lowest values were observed 3 days after irradiation. The thymus weight and thymocyte count in the irradiated mice returned to within normal range 7 to 8 days after irradiation (the values were almost the same as those before irradiation). Rapid rebound phenomena were observed in the rate of DNA-synthesizing cells and mitotic index in the thymus 5 days after irradiation. The results suggest that there is a close relationship between the incidence of leukemia and thymocyte activity after irradiation with x-rays; that is, there is a large percentage of juvenile cells with energetic proliferation capacity. (Tsunoda, M.)

Liraglutide Reduces Both Atherosclerosis and Kidney Inflammation in Moderately Uremic LDLr-/- Mice

DEFF Research Database (Denmark)

Bisgaard, Line S; Bosteen, Markus H; Fink, Lisbeth N

2016-01-01

Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis and atherosc......Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis...... aim was to examine effects of liraglutide on kidney fibrosis and atherosclerosis in a mouse model of moderate uremia (5/6 nephrectomy (NX)). Uremic (n = 29) and sham-operated (n = 14) atherosclerosis-prone low density lipoprotein receptor knockout mice were treated with liraglutide (1000 μg/kg, s.......c. once daily) or vehicle for 13 weeks. As expected, uremia increased aortic atherosclerosis. In the remnant kidneys from NX mice, flow cytometry revealed an increase in the number of monocyte-like cells (CD68+F4/80-), CD4+, and CD8+ T-cells, suggesting that moderate uremia induced kidney inflammation...

Hypophysectomy eliminates and growth hormone (GH) maintains the midpregnancy elevation in GH receptor and serum binding protein in the mouse

International Nuclear Information System (INIS)

Sanchez-Jimenez, F.; Fielder, P.J.; Martinez, R.R.; Smith, W.C.; Talamantes, F.

1990-01-01

[ 125 I]Iodomouse GH [( 125 I]iodo-mGH) binding to samples of serum and hepatic microsomal membranes was measured in hypophysectomized pregnant, sham-operated pregnant, intact pregnant, and intact adult virgin mice. Surgeries were carried out on day 11 of pregnancy, and the animals were killed on day 14. The binding of mGH to both serum and hepatic microsomal membranes of intact virgin mice was much lower than to those of intact pregnant mice. In hypophysectomized mice, the mGH-binding capacity of both serum and hepatic microsomes decreased to values similar to those of nonpregnant mice. No significant differences were observed between intact and sham-operated pregnant animals in the maternal serum mGH concentration, the serum GH-binding protein concentration, or the hepatic GH receptor concentration. GH receptor and binding protein-encoding mRNAs were also higher in intact and sham-operated pregnant mice than in virgin and hypophysectomized mice. Hypophysectomized mice were treated with 200 micrograms/day bovine GH, administered by osmotic minipump; after 3 days of treatment, a significant elevation of hepatic GH receptor and serum GH-binding protein levels was observed. These results demonstrate an up-regulation of hepatic GH receptors and serum GH-binding protein by GH during pregnancy in the mouse

Effect of acupuncture for radioactive-iodine-induced anorexia in thyroid cancer patients: a randomized, double-blinded, sham-controlled pilot study.

Science.gov (United States)

Jeon, Ju-Hyun; Yoon, Jeungwon; Cho, Chong-Kwan; Jung, In-Chul; Kim, Sungchul; Lee, Suk-Hoon; Yoo, Hwa-Seung

2015-05-01

The aim of this study is to evaluate the efficacy and safety of acupuncture for radioactive iodine (RAI)-induced anorexia in thyroid cancer patients. Fourteen thyroid cancer patients with RAI-induced anorexia were randomized to a true acupuncture or sham acupuncture group. Both groups were given 6 true or sham acupuncture treatments in 2 weeks. Outcome measures included the change of the Functional Assessment of Anorexia and Cachexia Treatment (FAACT; Anorexia/Cachexia Subscale [ACS], Functional Assessment of Cancer Therapy-General [FACT-G]), Visual Analogue Scale (VAS), weight, body mass index (BMI), ACTH, and cortisol levels. The mean FAACT ACS scores of the true and sham acupuncture groups increased from baseline to exit in intention-to-treat (ITT) and per protocol (PP) analyses; the true acupuncture group showed higher increase but with no statistical significance. Between groups, from baseline to the last treatment, statistically significant differences were found in ITT analysis of the Table of Index (TOI) score (P = .034) and in PP analysis of the TOI (P = .016), FACT-G (P = .045), FAACT (P = .037) scores. There was no significant difference in VAS, weight, BMI, ACTH, and cortisol level changes between groups. Although the current study is based on a small sample of participants, our findings support the safety and potential use of acupuncture for RAI-induced anorexia and quality of life in thyroid cancer patients. © The Author(s) 2015.

Auricular Acupressure for Managing Postoperative Pain and Knee Motion in Patients with Total Knee Replacement: A Randomized Sham Control Study

Directory of Open Access Journals (Sweden)

Ling-hua Chang

2012-01-01

Full Text Available Background. Postoperative pain management remains a significant challenge for all healthcare providers. A randomized controlled trial was conducted to examine the adjuvant effects of auricular acupressure on relieving postoperative pain and improving the passive range of motion in patients with total knee replacement (TKR. Method. Sixty-two patients who had undergone a TKR were randomly assigned to the acupressure group and the sham control group. The intervention was delivered three times a day for 3 days. A visual analog scale (VAS and the Short-Form McGill Pain Questionnaire were used to assess pain intensity. Pain medication consumption was recorded, and the knee motion was measured using a goniometer. Results. The patients experienced a moderately severe level of pain postoperatively (VAS 58.66 ± 20.35 while being on the routine PCA. No differences were found in pain scores between the groups at all points. However, analgesic drug usage in the acupressure group patients was significantly lower than in the sham control group (<0.05, controlling for BMI, age, and pain score. On the 3rd day after surgery, the passive knee motion in the acupressure group patients was significantly better than in the sham control group patients (<0.05, controlling for BMI. Conclusion. The application of auricular acupressure at specific therapeutic points significantly reduces the opioid analgesia requirement and improves the knee motion in patients with TKR.

The Hartree product and the description of local and global quantities in atomic systems: A study within Kohn-Sham theory

International Nuclear Information System (INIS)

Garza, Jorge; Nichols, Jeffrey A.; Dixon, David A.

2000-01-01

The Hartree product is analyzed in the context of Kohn-Sham theory. The differential equations that emerge from this theory are solved with the optimized effective potential using the Krieger, Li, and Iafrate approximation, in order to get a local potential as required by the ordinary Kohn-Sham procedure. Because the diagonal terms of the exact exchange energy are included in Hartree theory, it is self-interaction free and the exchange potential has the proper asymptotic behavior. We have examined the impact of this correct asymptotic behavior on local and global properties using this simple model to approximate the exchange energy. Local quantities, such as the exchange potential and the average local electrostatic potential are used to examine whether the shell structure in an atom is revealed by this theory. Global quantities, such as the highest occupied orbital energy (related to the ionization potential) and the exchange energy are also calculated. These quantities are contrasted with those obtained from calculations with the local density approximation, the generalized gradient approximation, and the self-interaction correction approach proposed by Perdew and Zunger. We conclude that the main characteristics in an atomic system are preserved with the Hartree theory. In particular, the behavior of the exchange potential obtained in this theory is similar to those obtained within other Kohn-Sham approximations. (c) 2000 American Institute of Physics

The pre-ischaemic neuroprotective effect of a novel polyamine antagonist, N1-dansyl-spermine in a permanent focal cerebral ischaemia model in mice.

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Li, Jun; Henman, Martin C; Doyle, Karen M; Strbian, Daniel; Kirby, Brian P; Tatlisumak, Turgut; Shaw, Graham G

2004-12-10

The polyamine sites on the NMDA receptor complex offer a therapeutic target for focal ischaemia, potentially devoid of most side effects associated with NMDA antagonists. In this study, we investigated the effect of a novel polyamine antagonist, N(1)-dansyl-spermine (0.5-10 mg kg(-1)) in a permanent focal cerebral ischaemia model in mice, and compared its effect to that of MK-801 (0.3-3 mg kg(-1)) following administration 30 min prior to ischaemia. A battery of histological and behavioural tests was employed following permanent middle cerebral artery occlusion to assess any neuroprotective effect. Following middle cerebral artery occlusion, N(1)-dansyl-spermine (1-5 mg kg(-1)) and MK-801 (1 or 3 mg kg(-1)) caused a comparable and significant reduction in the percentage hemisphere lesion volume. Similarly, both drugs significantly reduced oedema and neurological deficit score to a similar extent. Locomotor activity in MCAO mice was not significantly improved by MK-801 or N(1)-dansyl-spermine, although N(1)-dansyl-spermine induced a trend towards significant improvement. Significant improvement in rotarod performance was observed at neuroprotective doses with both drugs. Upon comparison of the profile of effects, N(1)-dansyl-spermine at least matched the effectiveness of MK-801 as a neuroprotective agent in this model. In addition, in sham-operated control mice, N(1)-dansyl-spermine was well tolerated, in contrast to the pronounced adverse effects of MK-801 on locomotor activity and rotarod performance. In conclusion, this study has shown that N(1)-dansyl-spermine is as effective a neuroprotective drug as MK-801 in this model. Moreover, in contrast to MK-801, N(1)-dansyl-spermine could be a promising therapeutic candidate for stroke as it is well tolerated at neuroprotective doses in sham-operated animals.

Attribution-Based Nocebo Effects. Perceived Effects of a Placebo Pill and a Sham Magnetic Field on Cognitive Performance and Somatic Symptoms.

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Szemerszky, Renáta; Dömötör, Zsuzsanna; Berkes, Tímea; Köteles, Ferenc

2016-04-01

Negative non-specific (nocebo-like) effects of medications and electromagnetic fields are often described as results of mistaken attribution. The current study aimed to find empirical evidence supporting this theory. Participants completed questionnaires assessing modern health worries, health anxiety, and somatosensory amplification, were assigned to one of three conditions (placebo pill with sedative information, sham magnetic field, or control), and completed a 14-min vigilance task. Changes in physiological arousal (heart rate, heart rate variability, and skin conductance) and reported symptoms were also measured. Finally, causal attributions concerning cognitive performance and reported symptoms were assessed. No increase in symptom reports and physiological arousal was measured in the two intervention groups. A perceived negative effect on cognitive performance was attributed to both sham conditions, and attributions were connected to modern health worries. A proportion of reported symptoms was ascribed to the placebo pill but not to the sham magnetic field. Symptom attributions were not related to any assessed psychological variables. An aroused physiological state is not necessary for the automatic causal attribution process. Negative effects attributed to medication and environmental factors can be regarded as unavoidable side effects of human cognitive-emotional functioning; they might be alleviated, but cannot be completely eradicated.

Repetitive Transcranial Magnetic Stimulation Improved Symptoms of Obsessive-Compulsive Disorder, but Also Cognitive Performance: Results from a Randomized Clinical Trial with a Cross-Over Design and Sham Condition.

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Jahangard, Leila; Haghighi, Mohammad; Shyayganfard, Mehran; Ahmadpanah, Mohammad; Sadeghi Bahmani, Dena; Bajoghli, Hafez; Holsboer-Trachsler, Edith; Brand, Serge

2016-01-01

There is some evidence that repetitive transcranial magnetic stimulation (rTMS) is an effective method of treating patients suffering from obsessive-compulsive disorder (OCD). Here, we tested the hypothesis that rTMS has a positive impact both on symptom severity and cognitive performance in such patients. Specifically, short-term verbal processing speed and flexibility were assessed. Ten patients suffering from refractory OCD and treated with standard medication were randomly assigned either to a treatment-first or to a sham-first condition. At baseline and after 2 and 4 weeks, symptom severity (experts' ratings) and cognitive performance (auditory perception, visual perception, short-term memory, and processing speed) were assessed. After 2 weeks, the treatment condition switched to the sham condition, and the sham condition switched to the treatment condition. Under treatment but not under sham conditions, symptom severity reduced. Moreover, cognitive performance improved in parallel. rTMS is a safe and efficient treatment for patients suffering from refractory OCD; symptoms and cognitive performance improved in parallel. © 2016 S. Karger AG, Basel.

Inhibition of IKKβ in enterocytes exacerbates sepsis-induced intestinal injury and worsens mortality.

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Dominguez, Jessica A; Samocha, Alexandr J; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Coopersmith, Craig M

2013-10-01

Nuclear factor-κB is a critical regulator of cell-survival genes and the host inflammatory response. The purpose of this study was to investigate the role of enterocyte-specific NF-kB in sepsis through selective ablation of IkB kinase. Prospective, randomized controlled study. Animal laboratories in university medical centers. Mice lacking functional NF-kB in their intestinal epithelium (Vil-Cre/Ikkβ) and wild-type mice were subjected to sham laparotomy or cecal ligation and puncture. Animals were killed at 24 hours or followed 7 days for survival. Septic wild-type mice had decreased villus length compared with sham mice, whereas villus atrophy was further exacerbated in septic Vil-Cre/Ikkβ mice. Sepsis induced an increase in intestinal epithelial apoptosis compared with sham mice, which was further exacerbated in Vil-Cre/Ikkβ mice. Sepsis induced intestinal hyperpermeability in wild-type mice compared with sham mice, which was further exacerbated in septic Vil-Cre/Ikkβ mice. This was associated with increased intestinal expression of claudin-2 in septic wild-type mice, which was further increased in septic Vil-Cre/Ikkβ mice. Both, pro-inflammatory and anti-inflammatory cytokines were increased in serum following cecal ligation and puncture, and interleukin 10 and monocyte chemoattractant protein-1 levels were higher in septic Vil-Cre/Ikkβ mice than in septic wild-type mice. All septic mice were bacteremic, but no differences in bacterial load were identified between wild-type and Vil-Cre/Ikkβ mice. To determine the functional significance of these results, animals were followed for survival. Septic wild-type mice had lower mortality than septic Vil-Cre/Ikkβ mice (47% vs 80%, p<0.05). Antitumor necrosis factor administration decreased intestinal apoptosis, permeability, and mortality in wild-type septic mice, and a similar improvement in intestinal integrity and survival were seen when antitumor necrosis factor was given to Vil-Cre/Ikkβ mice. Enterocyte

Inhibition of IKKß in enterocytes exacerbates sepsis-induced intestinal injury and worsens mortality

Science.gov (United States)

Dominguez, Jessica A.; Samocha, Alexandr J.; Liang, Zhe; Burd, Eileen M.; Farris, Alton B.; Coopersmith, Craig M.

2013-01-01

Objective NF-kB is a critical regulator of cell survival genes and the host inflammatory response. The purpose of this study was to investigate the role of enterocyte-specific NF-kB in sepsis through selective ablation of IkB kinase (IKK)-ß. Design Prospective, randomized, controlled study. Setting Animal laboratories in university medical centers. Subjects and Interventions Mice lacking functional NF-kB in their intestinal epithelium (Vil-Cre/Ikkßf/Δ) and wild type (WT) mice were subjected to sham laparotomy or cecal ligation and puncture (CLP). Animals were sacrified at 24 hours or followed seven days for survival. Measurements and Main Results Septic WT mice had decreased villus length compared to sham mice while villus atrophy was further exacerbated in septic Vil-Cre/Ikkßf/Δ mice. Sepsis induced an increase in intestinal epithelial apoptosis compared to sham mice which was further exacerbated in Vil-Cre/Ikkßf/Δ mice. Sepsis induced intestinal hyperpermeability in WT mice compared to sham mice, which was further exacerbated in septic Vil-Cre/Ikkßf/Δ mice. This was associated with increased intestinal expression of claudin-2 in septic WT mice, which was further increased in septic Vil-Cre/Ikkßf/Δ mice. Both, pro-inflammatory and anti-inflammatory cytokines were increased in serum following CLP, and IL-10 and MCP-1 levels were higher in septic Vil-Cre/Ikkßf/Δ mice than septic WT mice. All septic mice were bacteremic, but no differences in bacterial load were identified between WT and Vil-Cre/Ikkßf/Δ mice. To determine the functional significance of these results, animals were followed for survival. Septic WT mice had lower mortality than septic Vil-Cre/Ikkßf/Δ mice (47% vs. 80%, p<0.05). Anti-TNF administration decreased intestinal apoptosis, permeability and mortality in WT septic mice and a similar improvement in intestinal integrity and survival were seen when anti-TNF was given to Vil-Cre/Ikkßf/Δ mice. Conclusions Enterocyte-specific NF

Evolution of elderly patients who underwent cardiac surgery with cardiopulmonary bypass

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Alain Moré Duarte

2016-01-01

Full Text Available Introduction: There is a steady increase in the number of elderly patients with severe cardiovascular diseases who require a surgical procedure to recover some quality of life that allows them a socially meaningful existence, despite the risks.Objectives: To analyze the behavior of elderly patients who underwent cardiac surgery with cardiopulmonary bypass.Method: A descriptive, retrospective, cross-sectional study was conducted with patients over 65 years of age who underwent surgery at the Cardiocentro Ernesto Che Guevara, in Santa Clara, from January 2013 to March 2014.Results: In the study, 73.1% of patients were men; and there was a predominance of subjects between 65 and 70 years of age, accounting for 67.3%. Coronary artery bypass graft was the most prevalent type of surgery and had the longest cardiopulmonary bypass times. Hypertension was present in 98.1% of patients. The most frequent postoperative complications were renal dysfunction and severe low cardiac output, with 44.2% and 34.6% respectively.Conclusions: There was a predominance of men, the age group of 65 to 70 years, hypertension, and patients who underwent coronary artery bypass graft with prolonged cardiopulmonary bypass. Renal dysfunction was the most frequent complication.

Postsurgical food and water consumption, fecal corticosterone metabolites, and behavior assessment as noninvasive measures of pain in vasectomized BALB/c mice

DEFF Research Database (Denmark)

Jacobsen, Kirsten R; Kalliokoski, Otto; Teilmann, Anne C

2012-01-01

Recognition of pain and stress is a common challenge when working with laboratory mice. The aim of the current study was to identify noninvasive parameters to assess the severity and duration of possible pain and stress after vasectomy in BALB/c mice. Mice underwent isoflurane anesthesia......-related behaviors, but not FCM, may be useful as noninvasive parameters to assess postoperative pain and stress in vasectomized mice....... group compared with mice given anesthesia only. FCM were elevated the first day after anesthesia in the control mice but not in the vasectomized group. Vasectomy resulted in behavioral changes that were not seen in the group that was anesthetized only. In conclusion, food and water consumption and pain...

BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway.

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Chen, Mei-Rong; Dai, Ping; Wang, Shu-Fen; Song, Shu-Hua; Wang, Hang-Ping; Zhao, Ya; Wang, Ting-Hua; Liu, Jia

2016-10-01

Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up-regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT.

Time- and task-dependent non-neural effects of real and sham TMS.

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Felix Duecker

Full Text Available Transcranial magnetic stimulation (TMS is widely used in experimental brain research to manipulate brain activity in humans. Next to the intended neural effects, every TMS pulse produces a distinct clicking sound and sensation on the head which can also influence task performance. This necessitates careful consideration of control conditions in order to ensure that behavioral effects of interest can be attributed to the neural consequences of TMS and not to non-neural effects of a TMS pulse. Surprisingly, even though these non-neural effects of TMS are largely unknown, they are often assumed to be unspecific, i.e. not dependent on TMS parameters. This assumption is inherent to many control strategies in TMS research but has recently been challenged on empirical grounds. Here, we further develop the empirical basis of control strategies in TMS research. We investigated the time-dependence and task-dependence of the non-neural effects of TMS and compared real and sham TMS over vertex. Critically, we show that non-neural TMS effects depend on a complex interplay of these factors. Although TMS had no direct neural effects, both pre- and post-stimulus TMS time windows modulated task performance on both a sensory detection task and a cognitive angle judgment task. For the most part, these effects were quantitatively similar across tasks but effect sizes were clearly different. Moreover, the effects of real and sham TMS were almost identical with interesting exceptions that shed light on the relative contribution of auditory and somato-sensory aspects of a TMS pulse. Knowledge of such effects is of critical importance for the interpretation of TMS experiments and helps deciding what constitutes an appropriate control condition. Our results broaden the empirical basis of control strategies in TMS research and point at potential pitfalls that should be avoided.

The influence of ictal cutaneous allodynia on the response to occipital transcutaneous electrical stimulation in chronic migraine and chronic tension-type headache: a randomized, sham-controlled study.

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Bono, F; Salvino, D; Mazza, M R; Curcio, M; Trimboli, M; Vescio, B; Quattrone, A

2015-04-01

The objective of this article is to determine whether cutaneous allodynia (CA) influences the response to treatment with occipital transcutaneous electrical stimulation (OTES) in chronic migraine (CM) and chronic tension-type headache (CTTH). One hundred and sixty consecutive patients with CM or CTTH were randomized to be treated with real or sham OTES stimulation three times a day for two consecutive weeks. All patients completed the validated 12-item allodynia symptom checklist for assessing the presence and the severity of CA during headache attack. Primary end-point was change (≥50%) in number of monthly headache-free days. There was a significant difference in the percentage of responders in the real OTES compared with sham OTES group (p headache-free days in the allodynic patients with CM and CTTH treated both with real and sham OTES, while the number of headache-free days per month was significantly reduced in the real (86%) but not in the sham group (7%) of non-allodynic patients with CTTH and CM. Severe CA is associated with decreased response to treatment with OTES in patients with CM and CTTH. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

Science.gov (United States)

Liang, Zhe; Xie, Yan; Dominguez, Jessica A; Breed, Elise R; Yoseph, Benyam P; Burd, Eileen M; Farris, Alton B; Davidson, Nicholas O; Coopersmith, Craig M

2014-01-01

Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO) exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week) Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis. Aged (20-24 months) Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival. In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005). Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice. Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice.

Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

Directory of Open Access Journals (Sweden)

Zhe Liang

Full Text Available Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis.Aged (20-24 months Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival.In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005. Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice.Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice.

Using the Mouse Grimace Scale to Reevaluate the Efficacy of Postoperative Analgesics in Laboratory Mice

Science.gov (United States)

Matsumiya, Lynn C; Sorge, Robert E; Sotocinal, Susana G; Tabaka, John M; Wieskopf, Jeffrey S; Zaloum, Austin; King, Oliver D; Mogil, Jeffrey S

2012-01-01

Postoperative pain management in animals is complicated greatly by the inability to recognize pain. As a result, the choice of analgesics and their doses has been based on extrapolation from greatly differing pain models or the use of measures with unclear relevance to pain. We recently developed the Mouse Grimace Scale (MGS), a facial-expression–based pain coding system adapted directly from scales used in nonverbal human populations. The MGS has shown to be a reliable, highly accurate measure of spontaneous pain of moderate duration, and therefore is particularly useful in the quantification of postoperative pain. In the present study, we quantified the relative intensity and duration of postoperative pain after a sham ventral ovariectomy (laparotomy) in outbred mice. In addition, we compiled dose–response data for 4 commonly used analgesics: buprenorphine, carprofen, ketoprofen, and acetaminophen. We found that postoperative pain in mice, as defined by facial grimacing, lasts for 36 to 48 h, and appears to show relative exacerbation during the early dark (active) photophase. We find that buprenorphine was highly effective in inhibiting postoperative pain-induced facial grimacing in mice at doses equal to or lower than current recommendations, that carprofen and ketoprofen are effective only at doses markedly higher than those currently recommended, and that acetaminophen was ineffective at any dose used. We suggest the revision of practices for postoperative pain management in mice in light of these findings. PMID:22330867

Hesperetin-5,7,3'-O-triacetate suppresses airway hyperresponsiveness in ovalbumin-sensitized and challenged mice without reversing xylazine/ketamine-induced anesthesia in normal mice.

Science.gov (United States)

Yang, You-Lan; Chen, Chi-Li; Chen, Chi-Ming; Ko, Wun-Chang

2017-05-30

We recently reported that hesperetin-5,7,3'-O-triacetate (HTA) dually inhibited phosphodiesterase (PDE)3/4 with a therapeutic ratio of 20.8. The application and development of PDE4 inhibitors for treating asthma or COPD are limited by their side effects, such as nausea, vomiting and gastric hypersecretion. PDE4 inhibitors were reported to reverse xylazine/ketamine-induced anesthesia in rats and triggered vomiting in ferrets. Thus the reversing effect of HTA on xylazine/ketamine-induced anesthesia in mice was studied to assess emetic effect of HTA. The aim of this study was to prove the therapeutic effect of HTA without vomiting effect at an effective dose for treating COPD. Ten female BALB/c mice in each group were sensitized by ovalbumin (OVA) on days 0 and 14. On day 21, these mice were emphasized the sensitization by Freund's complete adjuvant. Mice were challenged by 1% OVA nebulization on days 28, 29, and 30. Airway hyperresponsiveness (AHR) was assessed on day 32 in each group, using the FlexiVent system to determine airway resistance (R L ) and lung dynamic compliance (C dyn ) in anesthetized ovalbumin (OVA)-sensitized and challenged mice. Each group was orally administered HTA (10 ~ 100 μmol/kg), roflumilast (1 and 5 mg/kg) or vehicles (controls) 2 h before and 6 and 24 h after OVA provocation. For comparison, sham-treated mice were challenged with saline instead of 1% OVA. The ability to reverse xylazine/ketamine-induced anesthesia by HTA or roflumilast for 3 h was determined in normal mice. We used roflumilast, a selective PDE4 inhibitor and bronchodilator for severe COPD approved by the US Food and Drug Administration, as a reference drug. In the results, HTA (100 μmol/kg, p.o.) or roflumilast (5 mg/kg, p.o.) significantly suppressed all R L values of MCh at 0.78 ~ 25 mg/mL and enhanced C dyn values of MCh at 3.125 ~ 25 mg/mL compared to OVA-sensitized and -challenged control mice. Orally administered 1, 3 or 10 mg/kg roflumilast

A novel platelet activating factor receptor antagonist reduces cell infiltration and expression of inflammatory mediators in mice exposed to desiccating conditions after PRK.

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Esquenazi, Salomon; He, Jiucheng; Li, Na; Bazan, Nicolas G; Esquenazi, Isi; Bazan, Haydee E P

2009-01-01

To study the contribution of a novel PAF receptor antagonist LAU-0901 in the modulation of the increased inflammatory response in mice exposed to dessicating conditions (DE) after PRK. Eighty 13-14 week old female Balb/C mice were used. They were divided into two groups: One group was treated with LAU-0901 topical drops. The other group was treated with vehicle. In each group ten mice served as controls and ten were placed in DE. The other twenty mice underwent bilateral PRK and were divided in two additional groups: ten mice remained under normal conditions (NC) and the other ten were exposed to DE. After 1 week all animals underwent in vivo confocal microscopy, immunostaining and western blotting analysis. Confocal microscopy showed an increased number of reflective structures in the corneal epithelium after PRK and exposure to DE in eyes treated with vehicle as compared to eyes treated with LAU-090). Significant decrease of COX-2 and Arginase I expression and reduced alpha SMA cells was observed after PRK and exposure to DE in eyes treated with LAU-0901. Exposure of mice to a DE after PRK increases the epithelial turnover rate. PAF is involved in the inflammatory cell infiltration and expression of inflammatory cytokines that follow PRK under DE.

Open-system Kohn-Sham density functional theory.

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Zhou, Yongxi; Ernzerhof, Matthias

2012-03-07

A simple model for electron transport through molecules is provided by the source-sink potential (SSP) method [F. Goyer, M. Ernzerhof, and M. Zhuang, J. Chem. Phys. 126, 144104 (2007)]. In SSP, the boundary conditions of having an incoming and outgoing electron current are enforced through complex potentials that are added to the Hamiltonian. Depending on the sign of the imaginary part of the potentials, current density is generated or absorbed. In this way, a finite system can be used to model infinite molecular electronic devices. The SSP has originally been developed for the Hückel method and subsequently it has been extended [F. Goyer and M. Ernzerhof, J. Chem. Phys. 134, 174101 (2011)] to the Hubbard model. Here we present a step towards its generalization for first-principles electronic structure theory methods. In particular, drawing on our earlier work, we discuss a new generalized density functional theory for complex non-Hermitian Hamiltonians. This theory enables us to combine SSP and Kohn-Sham theory to obtain a method for the description of open systems that exchange current density with their environment. Similarly, the Hartree-Fock method is extended to the realm of non-Hermitian, SSP containing Hamiltonians. As a proof of principle, we present the first applications of complex-density functional theory (CODFT) as well as non-Hermitian Hartree-Fock theory to electron transport through molecules. © 2012 American Institute of Physics

Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.

Science.gov (United States)

Townsend, Raymond R; Mahfoud, Felix; Kandzari, David E; Kario, Kazuomi; Pocock, Stuart; Weber, Michael A; Ewen, Sebastian; Tsioufis, Konstantinos; Tousoulis, Dimitrios; Sharp, Andrew S P; Watkinson, Anthony F; Schmieder, Roland E; Schmid, Axel; Choi, James W; East, Cara; Walton, Anthony; Hopper, Ingrid; Cohen, Debbie L; Wilensky, Robert; Lee, David P; Ma, Adrian; Devireddy, Chandan M; Lea, Janice P; Lurz, Philipp C; Fengler, Karl; Davies, Justin; Chapman, Neil; Cohen, Sidney A; DeBruin, Vanessa; Fahy, Martin; Jones, Denise E; Rothman, Martin; Böhm, Michael

2017-11-11

Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; prenal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

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Nieman, Brian J., E-mail: brian.nieman@utoronto.ca [Department of Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Ontario Institute for Cancer Research, Toronto, Ontario (Canada); Guzman, A. Elizabeth de [Department of Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Gazdzinski, Lisa M. [Department of Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Ontario (Canada); Lerch, Jason P. [Department of Neurosciences & Mental Health, Hospital for Sick Children, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chakravarty, M. Mallar [Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec (Canada); Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, Quebec (Canada); Pipitone, Jon [Kimel Family Translational Imaging Genetics Research Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario (Canada); Strother, Douglas [Alberta Children' s Hospital, Calgary, Alberta (Canada); Departments of Oncology and Pediatrics, University of Calgary, Calgary, Alberta (Canada); Fryer, Chris [Division of Oncology/Hematology/BMT British Columbia Children' s Hospital and British Columbia Women' s Hospital and Health Centre, Vancouver, British Columbia (Canada); Department of Pediatrics, University of British Columbia, Vancouver, British Columbia (Canada); Bouffet, Eric [Department of Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Ontario (Canada); Department of Paediatrics, University of Toronto, Toronto, Ontario (Canada); and others

2015-11-15

Purpose: Pediatric patients treated with cranial radiation are at high risk of developing lasting cognitive impairments. We sought to identify anatomical changes in both gray matter (GM) and white matter (WM) in radiation-treated patients and in mice, in which the effect of radiation can be isolated from other factors, the time course of anatomical change can be established, and the effect of treatment age can be more fully characterized. Anatomical results were compared between species. Methods and Materials: Patients were imaged with T{sub 1}-weighted magnetic resonance imaging (MRI) after radiation treatment. Nineteen radiation-treated patients were divided into groups of 7 years of age and younger (7−) and 8 years and older (8+) and were compared to 41 controls. C57BL6 mice were treated with radiation (n=52) or sham treated (n=52) between postnatal days 16 and 36 and then assessed with in vivo and/or ex vivo MRI. In both cases, measurements of WM and GM volume, cortical thickness, area and volume, and hippocampal volume were compared between groups. Results: WM volume was significantly decreased following treatment in 7− and 8+ treatment groups. GM volume was unchanged overall, but cortical thickness was slightly increased in the 7− group. Results in mice mostly mirrored these changes and provided a time course of change, showing early volume loss and normal growth. Hippocampal volume showed a decreasing trend with age in patients, an effect not observed in the mouse hippocampus but present in the olfactory bulb. Conclusions: Changes in mice treated with cranial radiation are similar to those in humans, including significant WM and GM alterations. Because mice did not receive any other treatment, the similarity across species supports the expectation that radiation is causative and suggests mice provide a representative model for studying impaired brain development after cranial radiation and testing novel treatments.

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

International Nuclear Information System (INIS)

Nieman, Brian J.; Guzman, A. Elizabeth de; Gazdzinski, Lisa M.; Lerch, Jason P.; Chakravarty, M. Mallar; Pipitone, Jon; Strother, Douglas; Fryer, Chris; Bouffet, Eric

2015-01-01

Purpose: Pediatric patients treated with cranial radiation are at high risk of developing lasting cognitive impairments. We sought to identify anatomical changes in both gray matter (GM) and white matter (WM) in radiation-treated patients and in mice, in which the effect of radiation can be isolated from other factors, the time course of anatomical change can be established, and the effect of treatment age can be more fully characterized. Anatomical results were compared between species. Methods and Materials: Patients were imaged with T_1-weighted magnetic resonance imaging (MRI) after radiation treatment. Nineteen radiation-treated patients were divided into groups of 7 years of age and younger (7−) and 8 years and older (8+) and were compared to 41 controls. C57BL6 mice were treated with radiation (n=52) or sham treated (n=52) between postnatal days 16 and 36 and then assessed with in vivo and/or ex vivo MRI. In both cases, measurements of WM and GM volume, cortical thickness, area and volume, and hippocampal volume were compared between groups. Results: WM volume was significantly decreased following treatment in 7− and 8+ treatment groups. GM volume was unchanged overall, but cortical thickness was slightly increased in the 7− group. Results in mice mostly mirrored these changes and provided a time course of change, showing early volume loss and normal growth. Hippocampal volume showed a decreasing trend with age in patients, an effect not observed in the mouse hippocampus but present in the olfactory bulb. Conclusions: Changes in mice treated with cranial radiation are similar to those in humans, including significant WM and GM alterations. Because mice did not receive any other treatment, the similarity across species supports the expectation that radiation is causative and suggests mice provide a representative model for studying impaired brain development after cranial radiation and testing novel treatments.

Physical Meaning of Virtual Kohn-Sham Orbitals and Orbital Energies: An Ideal Basis for the Description of Molecular Excitations

NARCIS (Netherlands)

van Meer, R.; Gritsenko, O.V.; Baerends, E.J.

2014-01-01

In recent years, several benchmark studies on the performance of large sets of functionals in time-dependent density functional theory (TDDFT) calculations of excitation energies have been performed. The tested functionals do not approximate exact Kohn-Sham orbitals and orbital energies closely. We

Neutrophil extracellular traps promote deep vein thrombosis in mice

Science.gov (United States)

Brill, A.; Fuchs, T.A.; Savchenko, A.S.; Thomas, G.M.; Martinod, K.; De Meyer, S.F.; Bhandari, A.A.; Wagner, D.D.

2011-01-01

Summary Background Upon activation, neutrophils can release nuclear material known as neutrophil extracellular traps (NETs), which were initially described as a part of antimicrobial defense. Extracellular chromatin was recently reported to be pro-thrombotic in vitro and to accumulate in plasma and thrombi of baboons with experimental deep vein thrombosis (DVT). Objective To explore the source and role of extracellular chromatin in DVT. Methods We used an established murine model of DVT induced by flow restriction (stenosis) in the inferior vena cava (IVC). Results We demonstrate that the levels of extracellular DNA increase in plasma after 6 h IVC stenosis, compared to sham-operated mice. Immunohistochemical staining revealed the presence of Gr-1-positive neutrophils in both red (RBC-rich) and white (platelet-rich) parts of thrombi. Citrullinated histone H3 (CitH3), an element of NETs’ structure, was present only in the red part of thrombi and was frequently associated with the Gr-1 antigen. Immunofluorescent staining of thrombi showed proximity of extracellular CitH3 and von Willebrand factor (VWF), a platelet adhesion molecule crucial for thrombus development in this model. Infusion of Deoxyribonuclease 1 (DNase 1) protected mice from DVT after 6 h and also 48 h IVC stenosis. Infusion of an unfractionated mixture of calf thymus histones increased plasma VWF and promoted DVT early after stenosis application. Conclusions Extracellular chromatin, likely originating from neutrophils, is a structural part of a venous thrombus and both the DNA scaffold and histones appear to contribute to the pathogenesis of DVT in mice. NETs may provide new targets for DVT drug development. PMID:22044575

Liraglutide Reduces Both Atherosclerosis and Kidney Inflammation in Moderately Uremic LDLr-/- Mice.

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Line S Bisgaard

Full Text Available Chronic kidney disease (CKD leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis and atherosclerosis in uremic settings, insight into new treatment options with effects on both parameters is warranted. The GLP-1 analogue liraglutide improves glucose homeostasis, and is approved for treatment of type 2 diabetes. Animal studies suggest that GLP-1 also dampens inflammation and atherosclerosis. Our aim was to examine effects of liraglutide on kidney fibrosis and atherosclerosis in a mouse model of moderate uremia (5/6 nephrectomy (NX. Uremic (n = 29 and sham-operated (n = 14 atherosclerosis-prone low density lipoprotein receptor knockout mice were treated with liraglutide (1000 μg/kg, s.c. once daily or vehicle for 13 weeks. As expected, uremia increased aortic atherosclerosis. In the remnant kidneys from NX mice, flow cytometry revealed an increase in the number of monocyte-like cells (CD68+F4/80-, CD4+, and CD8+ T-cells, suggesting that moderate uremia induced kidney inflammation. Furthermore, markers of fibrosis (i.e. Col1a1 and Col3a1 were upregulated, and histological examinations showed increased glomerular diameter in NX mice. Importantly, liraglutide treatment attenuated atherosclerosis (~40%, p < 0.05 and reduced kidney inflammation in NX mice. There was no effect of liraglutide on expression of fibrosis markers and/or kidney histology. This study suggests that liraglutide has beneficial effects in a mouse model of moderate uremia by reducing atherosclerosis and attenuating kidney inflammation.

Cardioprotective Effects of QiShenYiQi Dripping Pills on Transverse Aortic Constriction-Induced Heart Failure in Mice.

Science.gov (United States)

Ruan, Guoran; Ren, Haojin; Zhang, Chi; Zhu, Xiaogang; Xu, Chao; Wang, Liyue

2018-01-01

QiShenYiQi dripping pills (QSYQ), a traditional Chinese medicine, are commonly used to treat coronary heart disease, and QSYQ was recently approved as a complementary treatment for ischemic heart failure in China. However, only few studies reported on whether QSYQ exerts a protective effect on heart failure induced by pressure overload. In this study, we explored the role of QSYQ in a mouse model of heart failure induced by transverse aortic constriction (TAC). Twenty-eight C57BL/6J mice were divided into four groups: Sham + NS group, Sham + QSYQ group, TAC + NS group, and TAC + QSYQ group. QSYQ dissolved in normal saline (NS) was administered intragastrically (3.5 mg/100 g/day) in the Sham + QSYQ and TAC + QSYQ groups. In the Sham + NS and TAC + NS groups, NS was provided every day intragastrically. Eight weeks after TAC, echocardiography, and cardiac catheterization were performed to evaluate the cardiac function, and immunofluorescent staining with anti-actinin2 antibody was performed to determine the structure of the myocardial fibers. Moreover, TUNEL staining and Masson trichrome staining were employed to assess the effects of QSYQ on cardiac apoptosis and cardiac fibrosis. Western blots and real-time polymerase chain reaction (PCR) were used to measure the expression levels of vascular endothelial growth factor (VEGF) in the heart, and immunohistochemical staining with anti-CD31 antibody was performed to explore the role of QSYQ in cardiac angiogenesis. Results showed that TAC-induced cardiac dysfunction and disrupted structure of myocardial fibers significantly improved after QSYQ treatment. Moreover, QSYQ treatment also significantly improved cardiac apoptosis and cardiac fibrosis in TAC-induced heart failure, which was accompanied by an increase in VEGF expression levels and maintenance of microvessel density in the heart. In conclusion, QSYQ exerts a protective effect on TAC-induced heart failure, which could be attributed to enhanced cardiac angiogenesis

Effects of real and sham whole-body mechanical vibration on spinal excitability at rest and during muscle contraction

NARCIS (Netherlands)

Hortobagyi, T.; Rider, P.; DeVita, P.

2014-01-01

We examined the effects of whole-body mechanical vibration (WBV) on indices of motoneuronal excitability at rest and during muscle contraction in healthy humans. Real and sham WBV at 30Hz had no effect on reflexes measured during muscle contraction. Real WBV at 30 and 50Hz depressed the H-reflex

Chronic social stress leads to altered sleep homeostasis in mice.

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Olini, Nadja; Rothfuchs, Iru; Azzinnari, Damiano; Pryce, Christopher R; Kurth, Salome; Huber, Reto

2017-06-01

Disturbed sleep and altered sleep homeostasis are core features of many psychiatric disorders such as depression. Chronic uncontrollable stress is considered an important factor in the development of depression, but little is known on how chronic stress affects sleep regulation and sleep homeostasis. We therefore examined the effects of chronic social stress (CSS) on sleep regulation in mice. Adult male C57BL/6 mice were implanted for electrocortical recordings (ECoG) and underwent either a 10-day CSS protocol or control handling (CON). Subsequently, ECoG was assessed across a 24-h post-stress baseline, followed by a 4-h sleep deprivation, and then a 20-h recovery period. After sleep deprivation, CSS mice showed a blunted increase in sleep pressure compared to CON mice, as measured using slow wave activity (SWA, electroencephalographic power between 1-4Hz) during non-rapid eye movement (NREM) sleep. Vigilance states did not differ between CSS and CON mice during post-stress baseline, sleep deprivation or recovery, with the exception of CSS mice exhibiting increased REM sleep during recovery sleep. Behavior during sleep deprivation was not affected by CSS. Our data provide evidence that CSS alters the homeostatic regulation of sleep SWA in mice. In contrast to acute social stress, which results in a faster SWA build-up, CSS decelerates the homeostatic build up. These findings are discussed in relation to the causal contribution of stress-induced sleep disturbance to depression. Copyright © 2017 Elsevier B.V. All rights reserved.

[Effects of chrysalis oil on learning, memory and oxidative stress in D-galactose-induced ageing model of mice].

Science.gov (United States)

Chen, Weiping; Yang, Qiongjie; Wei, Xing

2013-11-01

To investigate the effects of chrysalis oil on learning, memory and oxidative stress in D-galactose-induced ageing model of mice. Mice were injected intraperitoneally with D-galactose daily and received chrysalis oil intragastrically simultaneously for 30 d. Then mice underwent space navigation test and spatial probe test, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) activity and malondialdehyde (MDA) contents in mouse brain were measured. Compared to model group, escape latency in mice treated with 6 ml/kg*d chrysalis oil was significantly shorter (Pchrysalis oil were significantly increased (PChrysalis oil treatment (12ml/kg*d) significantly increased SOD and GSH-PX activity and reduced MDA contents in brain of D-galactose-induced aging mice. Chrysalis oil can improve the ability of learning and memory in D-galactose-induced aging mice, and inhibit peroxidation in brain tissue.

Understanding band gaps of solids in generalized Kohn-Sham theory.

Science.gov (United States)

Perdew, John P; Yang, Weitao; Burke, Kieron; Yang, Zenghui; Gross, Eberhard K U; Scheffler, Matthias; Scuseria, Gustavo E; Henderson, Thomas M; Zhang, Igor Ying; Ruzsinszky, Adrienn; Peng, Haowei; Sun, Jianwei; Trushin, Egor; Görling, Andreas

2017-03-14

The fundamental energy gap of a periodic solid distinguishes insulators from metals and characterizes low-energy single-electron excitations. However, the gap in the band structure of the exact multiplicative Kohn-Sham (KS) potential substantially underestimates the fundamental gap, a major limitation of KS density-functional theory. Here, we give a simple proof of a theorem: In generalized KS theory (GKS), the band gap of an extended system equals the fundamental gap for the approximate functional if the GKS potential operator is continuous and the density change is delocalized when an electron or hole is added. Our theorem explains how GKS band gaps from metageneralized gradient approximations (meta-GGAs) and hybrid functionals can be more realistic than those from GGAs or even from the exact KS potential. The theorem also follows from earlier work. The band edges in the GKS one-electron spectrum are also related to measurable energies. A linear chain of hydrogen molecules, solid aluminum arsenide, and solid argon provide numerical illustrations.

Development of heart failure is independent of K+ channel-interacting protein 2 expression

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Speerschneider, Tobias; Grubb, Søren; Metoska, Artina; Olesen, Søren-Peter; Calloe, Kirstine; Thomsen, Morten B

2013-01-01

Abnormal ventricular repolarization in ion channelopathies and heart disease is a major cause of ventricular arrhythmias and sudden cardiac death. K+ channel-interacting protein 2 (KChIP2) expression is significantly reduced in human heart failure (HF), contributing to a loss of the transient outward K+ current (Ito). We aim to investigate the possible significance of a changed KChIP2 expression on the development of HF and proarrhythmia. Transverse aortic constrictions (TAC) and sham operations were performed in wild-type (WT) and KChIP2−/− mice. Echocardiography was performed before and every 2 weeks after the operation. Ten weeks post-surgery, surface ECG was recorded and we paced the heart in vivo to induce arrhythmias. Afterwards, tissue from the left ventricle was used for immunoblotting. Time courses of HF development were comparable in TAC-operated WT and KChIP2−/− mice. Ventricular protein expression of KChIP2 was reduced by 70% after 10 weeks TAC in WT mice. The amplitudes of the J and T waves were enlarged in KChIP2−/− control mice. Ventricular effective refractory period, RR, QRS and QT intervals were longer in mice with HF compared to sham-operated mice of either genotype. Pacing-induced ventricular tachycardia (VT) was observed in 5/10 sham-operated WT mice compared with 2/10 HF WT mice with HF. Interestingly, and contrary to previously published data, sham-operated KChIP2−/− mice were resistant to pacing-induced VT resulting in only 1/10 inducible mice. KChIP2−/− with HF mice had similar low vulnerability to inducible VT (1/9). Our results suggest that although KChIP2 is downregulated in HF, it is not orchestrating the development of HF. Moreover, KChIP2 affects ventricular repolarization and lowers arrhythmia susceptibility. Hence, downregulation of KChIP2 expression in HF may be antiarrhythmic in mice via reduction of the fast transient outward K+ current. PMID:24099801

Serum Zn levels in dysphagic patients who underwent endoscopic gastrostomy for long term enteral nutrition

OpenAIRE

Adriana Santos, Carla; Fonseca, Jorge; Brito, José; Fernandes, Tânia; Gonçalves, Luísa; Sousa Guerreiro, António

2014-01-01

Background and aims: Dysphagic patients who underwent endoscopic gastrostomy (PEG) usually present protein-energy malnutrition, but little is known about micronutrient malnutrition. The aim of the present study was the evaluation of serum zinc in patients who underwent endoscopic gastrostomy and its relationship with serum proteins, whole blood zinc, and the nature of underlying disorder. Methods: From patients that underwent gastrostomy a blood sample was obtained minutes before the procedur...

Homogeneous immunoglobulins in the serum of irradiated and bone marrow reconstituted mice: the role of thymus and spleen

International Nuclear Information System (INIS)

Mink, J.G.; Radl, J.; Berg, P. van den; Muiswinkel, W.B. van; Oosterom, R. van.

1979-01-01

The influence of thymectomy and splenectomy on the frequency and class distribution of homogeneous immunoglobulins (H-Ig) in serum was studied in lethally irradiated (DBA/2 x C57B1/Rij)F 1 mice reconstituted with syngeneic bone marrow. During four follow-up periods in the first 9 months after transplantation, the sham-operated controls and splenectomized animals developed transient H-Ig in an average frequency of 14.2 and 15.7% respectively. There were no marked differences in the incidence of H-Ig within these two groups. In contrast, thymectomized mice and mice both thymectomized and splenectomized showed H-Ig in much higher frequencies (average percentages 31.6 and 36.5 respectively). The highest frequency of H-Ig was observed between 1.5 and 3.5 months after transplantation. H-Ig of the IgG1 and IgG2 subclasses were most frequent in all groups during the first 3.5 months. Later, H-Ig belonging to the IgM class also appeared in somewhat higher numbers. H-Ig of the IgA class was a very rare finding at any time. These results indicate that the presence of the thymus, but not necessarily of the spleen, is an important factor in the regulation of the immunoglobulin heterogeneity during the reconstitution of the immune system in lethally irradiated and bone marrow reconstituted mice. (author)

Prospective randomized controlled trial of an injectable esophageal prosthesis versus a sham procedure for endoscopic treatment of gastroesophageal reflux disease

NARCIS (Netherlands)

Fockens, P.; Cohen, L.; Edmundowicz, S.A.; Binmoeller, K.; Rothstein, R.I.; Smith, D.; Lin, E.; Nickl, N.; Overholt, B.; Kahrilas, P.J.; Vakil, N.; Abdel Aziz Hassan, A.M.; Lehman, G.A.

2010-01-01

This study aimed to assess whether endoscopic implantation of an injectable esophageal prosthesis, the Gatekeeper Reflux Repair System (GK), is a safe and effective therapy for controlling gastroesophageal reflux disease (GERD). A prospective, randomized, sham-controlled, single-blinded,

Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice

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Naoto Tokuyama

2015-06-01

Full Text Available We examined the individual and combined effects of teriparatide and anti-RANKL (receptor activator of nuclear factor κB ligand monoclonal antibody in ovariectomized mice. Three-month-old female C57BL/6 mice were ovariectomized (OVX or sham operated. Four weeks after OVX, they were assigned to 3 different groups to receive anti-RANKL monoclonal antibody (Ab alone (5 mg/kg single injection at 4 weeks after OVX, Ab group, teriparatide alone (80 μg/kg daily injection for 4 weeks from 4 weeks after OVX, PTH group, or mAb plus teriparatide (Ab + PTH group. Mice were sacrificed 8 weeks after OVX. Bone mineral density (BMD was measured at the femur and lumbar spine. Hind limbs were subjected to histological and histomorphometric analysis. Serum osteocalcin and CTX-I levels were measured to investigate the bone turnover. Compared with Ab group, Ab + PTH group showed a significant increase in BMD at distal femur and femoral shaft. Cortical bone volume was significantly increased in PTH and Ab + PTH groups compared with Ab group. Bone turnover in Ab + PTH group was suppressed to the same degree as in Ab group. The number of TRAP-positive multinucleated cells was markedly reduced in Ab and Ab + PTH groups. These results suggest that combined treatment of teriparatide with anti-RANKL antibody has additive effects on BMD in OVX mice compared with individual treatment.

Triptolide attenuates pressure overload-induced myocardial remodeling in mice via the inhibition of NLRP3 inflammasome expression

International Nuclear Information System (INIS)

Li, Rujun; Lu, Kuiying; Wang, Yao; Chen, Mingxing; Zhang, Fengyu; Shen, Hui; Yao, Deshan; Gong, Kaizheng; Zhang, Zhengang

2017-01-01

Triptolide is the predominant active component of the Chinese herb Tripterygium wilfordii Hook F (TwHF) that has been widely used to treat several chronic inflammatory diseases due to its immunosuppressive, anti-inflammatory, and anti-proliferative properties. In the present study, we elucidated the cardioprotective effects of triptolide against cardiac dysfunction and myocardial remodeling in chronic pressure-overloaded hearts. Furthermore, the potential mechanisms of triptolide were investigated. For this purpose, C57/BL6 mice were anesthetized and subjected to transverse aortic constriction (TAC) or sham operation. Six weeks after the operation, all mice were randomly divided into 4 groups: sham-operated with vehicle group, TAC with vehicle group, and TAC with triptolide (20 or 100 μg/kg/day intraperitoneal injection) groups. Our data showed that the levels of NLRP3 inflammasome were significantly increased in the TAC group and were associated with increased inflammatory mediators and profibrotic factor production, resulting in myocardial fibrosis, cardiomyocyte hypertrophy, and impaired cardiac function. Triptolide treatment attenuated TAC-induced myocardial remodeling, improved cardiac diastolic and systolic function, inhibited the NLRP3 inflammasome and downstream inflammatory mediators (IL-1β, IL-18, MCP-1, VCAM-1), activated the profibrotic TGF-β1 pathway, and suppressed macrophage infiltration in a dose-dependent manner. Our study demonstrated that the protective effect of triptolide against pressure overload in the heart may act by inhibiting the NLRP3 inflammasome-induced inflammatory response and activating the profibrotic pathway. - Highlights: • Chronic pressure overload increases expression of NLRP3 inflammasome in the heart. • Triptolide attenuates chronic pressure overload-induced myocardial remodeling. • The mechanism appears to involve inhibition of NLRP3 inflammasome expression. • Triptolide is a therapeutic candidate for

Acute airway effects of airborne formaldehyde in sensitized and non-sensitized mice housed in a dry or humid environment

Energy Technology Data Exchange (ETDEWEB)

Larsen, Søren Thor, E-mail: stl@nrcwe.dk; Wolkoff, Peder, E-mail: pwo@nrcwe.dk; Hammer, Maria, E-mail: mha@nrcwe.dk; Kofoed-Sørensen, Vivi, E-mail: vks@nrcwe.dk; Clausen, Per Axel, E-mail: pac@nrcwe.dk; Nielsen, Gunnar Damgård, E-mail: gdn@nrcwe.dk

2013-05-01

We investigated the role of air humidity and allergic sensitization on the acute airway response to inhaled formaldehyde (FA) vapor. Mice were sensitized to the immunogen ovalbumin (OVA) by three intraperitoneal injections followed by two aerosol challenges, giving rise to allergic airway inflammation. Control mice were sham sensitized by saline injections and challenged by saline aerosols. Once sensitized, the mice were housed at high (85–89%) or low (< 10%) relative humidity, respectively for 48 h prior to a 60-min exposure to either 0.4, 1.8 or about 5 ppm FA. Before, during and after exposure, breathing parameters were monitored. These included the specific markers of nose and lung irritations as well as the expiratory flow rate, the latter being a marker of airflow limitation. The sensory irritation response in the upper airways was not affected by allergic inflammation or changes in humidity. At high relative humidity, the OVA-sensitized mice had a decreased expiratory airflow rate compared to the saline control mice after exposure to approximately 5 ppm FA. This is in accordance with the observations that asthmatics are more sensitive than non-asthmatics to higher concentrations of airway irritants including FA. In the dry environment, the opposite trend was seen; here, the saline control mice had a significantly decreased expiratory airflow rate compared to OVA-sensitized mice when exposed to 1.8 and 4 ppm FA. We speculate that increased mucus production in the OVA-sensitized mice has increased the “scrubber effect” in the nose, consequently protecting the conducting and lower airways. - Highlights: ► Role of air humidity and allergy on sensitivity to an airway irritant was studied. ► In the humid environment, allergy amplified the effects of formaldehyde. ► In the dry environment, allergy reduced the effect of formaldehyde. ► Neither allergy nor humidity changed the formaldehyde-induced nasal irritation.

Acute airway effects of airborne formaldehyde in sensitized and non-sensitized mice housed in a dry or humid environment

International Nuclear Information System (INIS)

Larsen, Søren Thor; Wolkoff, Peder; Hammer, Maria; Kofoed-Sørensen, Vivi; Clausen, Per Axel; Nielsen, Gunnar Damgård

2013-01-01

We investigated the role of air humidity and allergic sensitization on the acute airway response to inhaled formaldehyde (FA) vapor. Mice were sensitized to the immunogen ovalbumin (OVA) by three intraperitoneal injections followed by two aerosol challenges, giving rise to allergic airway inflammation. Control mice were sham sensitized by saline injections and challenged by saline aerosols. Once sensitized, the mice were housed at high (85–89%) or low (< 10%) relative humidity, respectively for 48 h prior to a 60-min exposure to either 0.4, 1.8 or about 5 ppm FA. Before, during and after exposure, breathing parameters were monitored. These included the specific markers of nose and lung irritations as well as the expiratory flow rate, the latter being a marker of airflow limitation. The sensory irritation response in the upper airways was not affected by allergic inflammation or changes in humidity. At high relative humidity, the OVA-sensitized mice had a decreased expiratory airflow rate compared to the saline control mice after exposure to approximately 5 ppm FA. This is in accordance with the observations that asthmatics are more sensitive than non-asthmatics to higher concentrations of airway irritants including FA. In the dry environment, the opposite trend was seen; here, the saline control mice had a significantly decreased expiratory airflow rate compared to OVA-sensitized mice when exposed to 1.8 and 4 ppm FA. We speculate that increased mucus production in the OVA-sensitized mice has increased the “scrubber effect” in the nose, consequently protecting the conducting and lower airways. - Highlights: ► Role of air humidity and allergy on sensitivity to an airway irritant was studied. ► In the humid environment, allergy amplified the effects of formaldehyde. ► In the dry environment, allergy reduced the effect of formaldehyde. ► Neither allergy nor humidity changed the formaldehyde-induced nasal irritation

EFFECTS OF RUN TRAINING ON BONE DEVELOPMENT AND BONE MINERALIZATION IN GROWING MICE

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B Gönül

2011-06-01

Full Text Available We planned to study the body weights, bone sizes and bone mineral (Ca, Mg, Zn contents of growing mice subjected to treadmill training. Twelve 4-week-old male Swiss Albino mice were divided into sedentary and exercise groups. The mice were trained by running exercise on a flat bed treadmill with 15 m/min, 30 min/day motion, throughout 5 days per week, for 12 weeks. The body weight of animals, and length, fat-free dry weight and Ca, Mg, and Zn contents of bones were measured in both groups. Body weights of animals, and lengths and wet and dry weights of the femur and the tibia were significantly higher in the exercised group. Also, the Zn, Mg and Ca mineral contents of bones in the group that underwent exercise were higher than in the other group. Running exercise with a flat bed treadmill performed by the growing mice is an effective exercise mode, especially for bone morphology.

Depression-like behavior and mechanical allodynia are reduced by bis selenide treatment in mice with chronic constriction injury: a comparison with fluoxetine, amitriptyline, and bupropion.

Science.gov (United States)

Jesse, Cristiano R; Wilhelm, Ethel A; Nogueira, Cristina W

2010-12-01

Neuropathic pain is associated with significant co-morbidities, including depression, which impact considerably on the overall patient experience. Pain co-morbidity symptoms are rarely assessed in animal models of neuropathic pain. Neuropathic pain is characterized by hyperexcitability within nociceptive pathways and remains difficult to treat with standard analgesics. The present study determined the effect of bis selenide and conventional antidepressants (fluoxetine, amitriptyline, and bupropion) on neuropathic pain using mechanical allodynic and on depressive-like behavior. Male mice were subjected to chronic constriction injury (CCI) or sham surgery and were assessed on day 14 after operation. Mice received oral treatment with bis selenide (1-5 mg/kg), fluoxetine, amitriptyline, or bupropion (10-30 mg/kg). The response frequency to mechanical allodynia in mice was measured with von Frey hairs. Mice were evaluated in the forced swimming test (FST) test for depression-like behavior. The CCI procedure produced mechanical allodynia and increased depressive-like behavior in the FST. All of the drugs produced antiallodynic effects in CCI mice and produced antidepressant effects in control mice without altering locomotor activity. In CCI animals, however, only the amitriptyline and bis selenide treatments significantly reduced immobility in the FST. These data demonstrate an important dissociation between the antiallodynic and antidepressant effects in mice when tested in a model of neuropathic pain. Depressive behavior in CCI mice was reversed by bis selenide and amitriptyline but not by the conventional antidepressants fluoxetine and buproprion. Bis selenide was more potent than the other drugs tested for antidepressant-like and antiallodynic effects in mice.

Moderate injury in motor-sensory cortex causes behavioral deficits accompanied by electrophysiological changes in mice adulthood.

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Wei Ouyang

Full Text Available Moderate traumatic brain injury (TBI in children often happen when there's a sudden blow to the frontal bone, end with long unconscious which can last for hours and progressive cognitive deficits. However, with regard to the influences of moderate TBI during children adulthood, injury-induced alterations of locomotive ability, long-term memory performance, and hippocampal electrophysiological firing changes have not yet been fully identified. In this study, lateral fluid percussion (LFP method was used to fabricate moderate TBI in motor and somatosensory cortex of the 6-weeks-old mice. The motor function, learning and memory function, extracellular CA1 neural spikes were assessed during acute and subacute phase. Moreover, histopathology was performed on day post injury (DPI 16 to evaluate the effect of TBI on tissue and cell morphological changes in cortical and hippocampal CA1 subregions. After moderate LFP injury, the 6-weeks-old mice showed severe motor deficits at the early stage in acute phase but gradually recovered later during adulthood. At the time points in acute and subacute phase after TBI, novel object recognition (NOR ability and spatial memory functions were consistently impaired in TBI mice; hippocampal firing frequency and burst probability were hampered. Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop. These electrophysiological impacts were associated with substantially lowered NOR preference as compared to the sham group during adulthood. These results suggest that moderate TBI introduced at motorsenory cortex in 6-weeks-old mice causes obvious motor and cognitive deficits during their adulthood. While the locomotive ability progressively recovers, the cognitive deficits persisted while the mice mature as adult mice. The cognitive deficits may be attributed to the general suppressing of whole neural network, which could be labeled by marked reduction of excitability in hippocampal CA1

Moderate injury in motor-sensory cortex causes behavioral deficits accompanied by electrophysiological changes in mice adulthood.

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Ouyang, Wei; Yan, Qichao; Zhang, Yu; Fan, Zhiheng

2017-01-01

Moderate traumatic brain injury (TBI) in children often happen when there's a sudden blow to the frontal bone, end with long unconscious which can last for hours and progressive cognitive deficits. However, with regard to the influences of moderate TBI during children adulthood, injury-induced alterations of locomotive ability, long-term memory performance, and hippocampal electrophysiological firing changes have not yet been fully identified. In this study, lateral fluid percussion (LFP) method was used to fabricate moderate TBI in motor and somatosensory cortex of the 6-weeks-old mice. The motor function, learning and memory function, extracellular CA1 neural spikes were assessed during acute and subacute phase. Moreover, histopathology was performed on day post injury (DPI) 16 to evaluate the effect of TBI on tissue and cell morphological changes in cortical and hippocampal CA1 subregions. After moderate LFP injury, the 6-weeks-old mice showed severe motor deficits at the early stage in acute phase but gradually recovered later during adulthood. At the time points in acute and subacute phase after TBI, novel object recognition (NOR) ability and spatial memory functions were consistently impaired in TBI mice; hippocampal firing frequency and burst probability were hampered. Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop. These electrophysiological impacts were associated with substantially lowered NOR preference as compared to the sham group during adulthood. These results suggest that moderate TBI introduced at motorsenory cortex in 6-weeks-old mice causes obvious motor and cognitive deficits during their adulthood. While the locomotive ability progressively recovers, the cognitive deficits persisted while the mice mature as adult mice. The cognitive deficits may be attributed to the general suppressing of whole neural network, which could be labeled by marked reduction of excitability in hippocampal CA1 subregion.

Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice

International Nuclear Information System (INIS)

Ware, J.H.; Rusek, A.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X.S.; Kennedy, A.R.

2010-01-01

The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice.

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Ware, J H; Sanzari, J; Avery, S; Sayers, C; Krigsfeld, G; Nuth, M; Wan, X S; Rusek, A; Kennedy, A R

2010-09-01

The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

Megarectumsigma underwent surgery for chronic faecal impact action

International Nuclear Information System (INIS)

Canessa, C.; Gomez del Valle, M.; Caraballo, M.

2002-01-01

Seven patients with megarectumsigma underwent surgery for chronic faecal impaction,reviewing clinical diagnosis, aetiology and medical and surgical management.It is suggested medical management of chronic faecal impaction trying to achieve elective surgery.The curative surgery should include the resection of all pathologic bowel, but in Duhamel procedure and its modifications distal rectal tran section should be at the peritoneal reflection.Habr-Gama modification has shown to be technically easier and it has been communicated good functional results.Local unfavourable conditions may be resolve by staged surgery,which allows outline definitive bowel reconstruction after functional assessment

In Vivo MRI Measurement of Spinal Cord Displacement in the Thoracolumbar Region of Asymptomatic Subjects with Unilateral and Sham Straight Leg Raise Tests.

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M Rade

Full Text Available Normal displacement of the conus medullaris with unilateral and bilateral SLR has been quantified and the "principle of linear dependence" has been described.Explore whether previously recorded movements of conus medullaris with SLRs are i primarily due to transmission of tensile forces transmitted through the neural tissues during SLR or ii the result of reciprocal movements between vertebrae and nerves.Controlled radiologic study.Ten asymptomatic volunteers were scanned with a 1.5T magnetic resonance (MR scanner using T2 weighted spc 3D scanning sequences and a device that permits greater ranges of SLR. Displacement of the conus medullaris during the unilateral and sham SLR was quantified reliably with a randomized procedure. Conus displacement in response to unilateral and sham SLRs was quantified and the results compared.The conus displaced caudally in the spinal canal by 3.54±0.87 mm (mean±SD with unilateral (p≤.001 and proximally by 0.32±1.6 mm with sham SLR (p≤.542. Pearson correlations were higher than 0.99 for both intra- and inter-observer reliability and the observed power was 1 for unilateral SLRs and 0.054 and 0.149 for left and right sham SLR respectively.Four relevant points emerge from the presented data: i reciprocal movements between the spinal cord and the surrounding vertebrae are likely to occur during SLR in asymptomatic subjects, ii conus medullaris displacement in the vertebral canal with SLR is primarily due to transmission of tensile forces through the neural tissues, iii when tensile forces are transmitted through the neural system as in the clinical SLR, the magnitude of conus medullaris displacement prevails over the amount of bone adjustment.

HairMax LaserComb laser phototherapy device in the treatment of male androgenetic alopecia: A randomized, double-blind, sham device-controlled, multicentre trial.

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Leavitt, Matt; Charles, Glenn; Heyman, Eugene; Michaels, David

2009-01-01

The use of low levels of visible or near infrared light for reducing pain, inflammation and oedema, promoting healing of wounds, deeper tissue and nerves, and preventing tissue damage has been known for almost 40 years since the invention of lasers. The HairMax LaserComb is a hand-held Class 3R lower level laser therapy device that contains a single laser module that emulates 9 beams at a wavelength of 655 nm (+/-5%). The device uses a technique of parting the user's hair by combs that are attached to the device. This improves delivery of distributed laser light to the scalp. The combs are designed so that each of the teeth on the combs aligns with a laser beam. By aligning the teeth with the laser beams, the hair can be parted and the laser energy delivered to the scalp of the user without obstruction by the individual hairs on the scalp. The primary aim of the study was to assess the safety and effectiveness of the HairMax LaserComb laser phototherapy device in the promotion of hair growth and in the cessation of hair loss in males diagnosed with androgenetic alopecia (AGA). This double-blind, sham device-controlled, multicentre, 26-week trial randomized male patients with Norwood-Hamilton classes IIa-V AGA to treatment with the HairMax LaserComb or the sham device (2 : 1). The sham device used in the study was identical to the active device except that the laser light was replaced by a non-active incandescent light source. Of the 110 patients who completed the study, subjects in the HairMax LaserComb treatment group exhibited a significantly greater increase in mean terminal hair density than subjects in the sham device group (p laser phototherapy device for the treatment of AGA in males.

Efficacy of the RADPAD Protection Drape in Reducing Operators' Radiation Exposure in the Catheterization Laboratory: A Sham-Controlled Randomized Trial.

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Vlastra, Wieneke; Delewi, Ronak; Sjauw, Krischan D; Beijk, Marcel A; Claessen, Bimmer E; Streekstra, Geert J; Bekker, Robbert J; van Hattum, Juliette C; Wykrzykowska, Joanna J; Vis, Marije M; Koch, Karel T; de Winter, Robbert J; Piek, Jan J; Henriques, José P S

2017-11-01

Interventional cardiologists are increasingly exposed to radiation-induced diseases like cataract and the stochastic risk of left-sided brain tumors. The RADPAD is a sterile, disposable, lead-free shield placed on the patient with the aim to minimize operator-received scatter radiation. The objective of the trial was to examine the RADPAD's efficacy in a real-world situation. In the current, double-blind, sham-controlled, all-comer trial, patients undergoing diagnostic catheterization or percutaneous coronary interventions were randomized in a 1:1:1 ratio to a radiation absorbing shield (RADPAD), standard treatment (NOPAD), or a sham shield (SHAMPAD). The sham shield allowed testing for shield-induced radiation behavior. The primary outcome was the difference in relative exposure of the primary operator between the RADPAD and NOPAD arms and was defined as the ratio between operator's exposure (E in µSv) and patient exposure (dose area product in mGy·cm 2 ), measured per procedure. A total of 766 consecutive coronary procedures were randomized to the use of RADPAD (N=255), NOPAD (N=255), or SHAMPAD (N=256). The use of RADPAD was associated with a 20% reduction in relative operator exposure compared with that of NOPAD ( P =0.01) and a 44% relative exposure reduction compared with the use of a SHAMPAD ( P RADPAD radiation shield reduced operator radiation exposure compared with procedures with NOPAD or SHAMPAD. This study supports the routine use of RADPAD in the catheterization laboratory. URL: https://www.clinicaltrials.gov. Unique identifier: NCT03139968. © 2017 American Heart Association, Inc.

Effects of repetitive peripheral magnetic stimulation on upper-limb spasticity and impairment in patients with spastic hemiparesis: a randomized, double-blind, sham-controlled study.

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Krewer, Carmen; Hartl, Sandra; Müller, Friedemann; Koenig, Eberhard

2014-06-01

To investigate short-term and long-term effects of repetitive peripheral magnetic stimulation (rpMS) on spasticity and motor function. Monocentric, randomized, double-blind, sham-controlled trial. Neurologic rehabilitation hospital. Patients (N=66) with severe hemiparesis and mild to moderate spasticity resulting from a stroke or a traumatic brain injury. The average time ± SD since injury for the intervention groups was 26 ± 71 weeks or 37 ± 82 weeks. rpMS for 20 minutes or sham stimulation with subsequent occupational therapy for 20 minutes, 2 times a day, over a 2-week period. Modified Tardieu Scale and Fugl-Meyer Assessment (arm score), assessed before therapy, at the end of the 2-week treatment period, and 2 weeks after study treatment. Additionally, the Tardieu Scale was assessed after the first and before the third therapy session to determine any short-term effects. Spasticity (Tardieu >0) was present in 83% of wrist flexors, 62% of elbow flexors, 44% of elbow extensors, and 10% of wrist extensors. Compared with the sham stimulation group, the rpMS group showed short-term effects on spasticity for wrist flexors (P=.048), and long-term effects for elbow extensors (P<.045). Arm motor function (rpMS group: median 5 [4-27]; sham group: median 4 [4-9]) did not significantly change over the study period in either group, whereas rpMS had a positive effect on sensory function. Therapy with rpMS increases sensory function in patients with severe limb paresis. The magnetic stimulation, however, has limited effect on spasticity and no effect on motor function. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Comparison of radioprotective effects of caffeine and ascorbic acid in male mice

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Kim, Jin Kyu; Kim, Ji Hyang; Lee, Byoung Hun [KAERI, Taejon (Korea, Republic of); Yoon, Yong Dal [Hanyang Univ., Seoul (Korea, Republic of)

2003-04-01

The oxygen effect in radiation biology is well known. Since oxygen enhances radiation-induced biological damage, antioxidants should be radioprotectors. Ascorbic acid (vitamin C) or caffeine is an essential component in the diet of humans and a small range of other mammals. Radioprotective effects of vitamin C have been demonstrated in certain cells and animals, which would result from scavenging free radicals. Caffeine is the main psychoactive ingredient of coffee, tea, even coke with a high frequency of concurrent use in humans. Caffeine has been recently reported as a scavenger of hydroxyl radical in millimolar levels and a potently radioprotector in a chronically exposed rodent. This study investigates functional radioprotection of caffeine and ascorbic acid against gamma irradiation in male mice. Eight-week-old male C57BL/6N mice were irradiated with 6.5 Gy. A caffeine treated group was administered with 80 mg/kg body weight by i.p injection, a single exposure 1 hour before irradiation. Ascorbic acid was administered 330 mg/liter in drinking water through all the experimental period. The remaining mice were kept as sham controls. After collecting a serum from the experimental mice 6 hr after irradiation, qualitative analysis of testosterone was performed by means of radioimmunoassay (RIA). For histological investigation, testes were removed 1 week after irradiation and fixed in NBF. Fixed testes were processed for paraffin sections and stained by H-E. The circulating testosterone significantly decreased in all irradiated groups. The harmful effect of radiation on the body and organ weight and the appearance of semiferous tubules were significantly improved in the caffeine - or ascorbic acid-treated group. In conclusion, caffeine and ascorbic acid protected spermatogenesis from impairment against gamma radiation, acting as a radioprotector.

Comparison of radioprotective effects of caffeine and ascorbic acid in male mice

International Nuclear Information System (INIS)

Kim, Jin Kyu; Kim, Ji Hyang; Lee, Byoung Hun; Yoon, Yong Dal

2003-01-01

The oxygen effect in radiation biology is well known. Since oxygen enhances radiation-induced biological damage, antioxidants should be radioprotectors. Ascorbic acid (vitamin C) or caffeine is an essential component in the diet of humans and a small range of other mammals. Radioprotective effects of vitamin C have been demonstrated in certain cells and animals, which would result from scavenging free radicals. Caffeine is the main psychoactive ingredient of coffee, tea, even coke with a high frequency of concurrent use in humans. Caffeine has been recently reported as a scavenger of hydroxyl radical in millimolar levels and a potently radioprotector in a chronically exposed rodent. This study investigates functional radioprotection of caffeine and ascorbic acid against gamma irradiation in male mice. Eight-week-old male C57BL/6N mice were irradiated with 6.5 Gy. A caffeine treated group was administered with 80 mg/kg body weight by i.p injection, a single exposure 1 hour before irradiation. Ascorbic acid was administered 330 mg/liter in drinking water through all the experimental period. The remaining mice were kept as sham controls. After collecting a serum from the experimental mice 6 hr after irradiation, qualitative analysis of testosterone was performed by means of radioimmunoassay (RIA). For histological investigation, testes were removed 1 week after irradiation and fixed in NBF. Fixed testes were processed for paraffin sections and stained by H-E. The circulating testosterone significantly decreased in all irradiated groups. The harmful effect of radiation on the body and organ weight and the appearance of semiferous tubules were significantly improved in the caffeine - or ascorbic acid-treated group. In conclusion, caffeine and ascorbic acid protected spermatogenesis from impairment against gamma radiation, acting as a radioprotector

Carotid body denervation prevents fasting hyperglycemia during chronic intermittent hypoxia.

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Shin, Mi-Kyung; Yao, Qiaoling; Jun, Jonathan C; Bevans-Fonti, Shannon; Yoo, Doo-Young; Han, Woobum; Mesarwi, Omar; Richardson, Ria; Fu, Ya-Yuan; Pasricha, Pankaj J; Schwartz, Alan R; Shirahata, Machiko; Polotsky, Vsevolod Y

2014-10-01

Obstructive sleep apnea causes chronic intermittent hypoxia (IH) and is associated with impaired glucose metabolism, but mechanisms are unknown. Carotid bodies orchestrate physiological responses to hypoxemia by activating the sympathetic nervous system. Therefore, we hypothesized that carotid body denervation would abolish glucose intolerance and insulin resistance induced by chronic IH. Male C57BL/6J mice underwent carotid sinus nerve dissection (CSND) or sham surgery and then were exposed to IH or intermittent air (IA) for 4 or 6 wk. Hypoxia was administered by decreasing a fraction of inspired oxygen from 20.9% to 6.5% once per minute, during the 12-h light phase (9 a.m.-9 p.m.). As expected, denervated mice exhibited blunted hypoxic ventilatory responses. In sham-operated mice, IH increased fasting blood glucose, baseline hepatic glucose output (HGO), and expression of a rate-liming hepatic enzyme of gluconeogenesis phosphoenolpyruvate carboxykinase (PEPCK), whereas the whole body glucose flux during hyperinsulinemic euglycemic clamp was not changed. IH did not affect glucose tolerance after adjustment for fasting hyperglycemia in the intraperitoneal glucose tolerance test. CSND prevented IH-induced fasting hyperglycemia and increases in baseline HGO and liver PEPCK expression. CSND trended to augment the insulin-stimulated glucose flux and enhanced liver Akt phosphorylation at both hypoxic and normoxic conditions. IH increased serum epinephrine levels and liver sympathetic innervation, and both increases were abolished by CSND. We conclude that chronic IH induces fasting hyperglycemia increasing baseline HGO via the CSN sympathetic output from carotid body chemoreceptors, but does not significantly impair whole body insulin sensitivity. Copyright © 2014 the American Physiological Society.

Effects of pre-natal X-ray exposure on learning behaviour of mice

International Nuclear Information System (INIS)

Frank, P.; Faber, U.; Budny, T.

1983-01-01

The authors investigated whether prenatal X-raying affects the learning behaviour of mice. For this purpose they irradiated mice of strain C57BL/6Ffm with 130 r at different points of the fetal phase. Unirradiated mice served as controls. The animals underwent two learning test series of 14 days each teaching them optical signs. The results of the test series show a distinctly inferior learning ability in the animals exposed to pre-natal irradiation as compared to unirradiated controls. The extent of the reduction of the learning ability depends on the stage of the pregnancy at the time of X-ray exposure. The greatest difference as compared to non-irradiated mice occurred in the animals irradiated at the earliest stage (13th/14th day of pregnancy). The results of the other test groups (15th/16th and 17th/18th day of pregnancy) exhibited less distinct, but still significant differences to the controls. Exposure at the latest period (17th/18th day) coincided with the smallest difference. (orig./MG) [de

Investigation of standard care versus sham Reiki placebo versus actual Reiki therapy to enhance comfort and well-being in a chemotherapy infusion center.

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Catlin, Anita; Taylor-Ford, Rebecca L

2011-05-01

To determine whether provision of Reiki therapy during outpatient chemotherapy is associated with increased comfort and well-being. Double-blind, randomized clinical controlled trial. Outpatient chemotherapy center. 189 participants were randomized to actual Reiki, sham Reiki placebo, or standard care. Patients receiving chemotherapy were randomly placed into one of three groups. Patients received either standard care, a placebo, or an actual Reiki therapy treatment. A demographic tool and pre- and post-tests were given before and after chemotherapy infusion. Reiki therapy, sham Reiki placebo therapy, standard care, and self-reported levels of comfort and well-being pre- and postintervention. Although Reiki therapy was statistically significant in raising the comfort and well-being of patients post-therapy, the sham Reiki placebo also was statistically significant. Patients in the standard care group did not experience changes in comfort and well-being during their infusion session. The findings indicate that the presence of an RN providing one-on-one support during chemotherapy was influential in raising comfort and well-being levels, with or without an attempted healing energy field. An attempt by clinic nurses to provide more designated one-to-one presence and support for patients while receiving their chemotherapy infusions could increase patient comfort and well-being.

Scanning Ultrasound (SUS Causes No Changes to Neuronal Excitability and Prevents Age-Related Reductions in Hippocampal CA1 Dendritic Structure in Wild-Type Mice.

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Robert John Hatch

Full Text Available Scanning ultrasound (SUS is a noninvasive approach that has recently been shown to ameliorate histopathological changes and restore memory functions in an Alzheimer's disease mouse model. Although no overt neuronal damage was reported, the short- and long-term effects of SUS on neuronal excitability and dendritic tree morphology had not been investigated. To address this, we performed patch-clamp recordings from hippocampal CA1 pyramidal neurons in wild-type mice 2 and 24 hours after a single SUS treatment, and one week and 3 months after six weekly SUS treatments, including sham treatments as controls. In both treatment regimes, no changes in CA1 neuronal excitability were observed in SUS-treated neurons when compared to sham-treated neurons at any time-point. For the multiple treatment groups, we also determined the dendritic morphology and spine densities of the neurons from which we had recorded. The apical trees of sham-treated neurons were reduced at the 3 month time-point when compared to one week; however, surprisingly, no longitudinal change was detected in the apical dendritic trees of SUS-treated neurons. In contrast, the length and complexity of the basal dendritic trees were not affected by SUS treatment at either time-point. The apical dendritic spine densities were reduced, independent of the treatment group, at 3 months compared to one week. Collectively, these data suggest that ultrasound can be employed to prevent an age-associated loss of dendritic structure without impairing neuronal excitability.

Regulatory effects of adenosine A2A receptors on psychomotor ability and mood behavior of mice

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Li JIANG

2011-07-01

Full Text Available Objective To explore the effects of gene knock-out,agonist or inhibitor of adenosine A2A receptor on the locomotor activity,and anxiety-or depression-like behavior of mice.Methods Male C57BL/6 mice,comprising those underwent gene knock-out of adenosine A2A receptor(A2AKO and their wild-type(WT littermates,were assigned into A2AKO group and WT group.Another batch of male C57BL/6,specific-pathogen-free(SPF mice,were assigned into SCH58261 group,CGS21680 group and control group.Mice of aforesaid 3 groups were transperitoneally administered with SCH58261,a specific inhibitor of adenosine A2A receptor at a dose of 2mg/kg,CGS21680,a specific agonist of adenosine A2A receptor at a dose of 0.5mg/kg,and vehicle(0.25ml,comprising DMSO and saline,respectively.Ten minutes after injection,mice of the 3 groups underwent open-field test,elevated plus-maze test and forced swimming test to detect their locomotor activity,anxiety-and depression-like behavior.Results a Compared with WT group,the total movement distance decreased(P 0.05.b Compared with control group,the total movement distance decreased and the stay time in the peripheral area increased significantly in the open field test(P 0.05.Conclusions The agonist of adenosine A2A receptor may depress the spontaneous motility and exploratory behavior,and exacerbate the anxiety and depression,and it simulates the effect induced by knock-out of A2A receptor gene,but it is opposite to the effect induced by A2A receptor inhibitor.

Comment on 'Asymptotic form of the Kohn-Sham correlation potential'

International Nuclear Information System (INIS)

Holas, A.

2008-01-01

For finite systems that have the energetically highest-occupied molecular orbital (HOMO) with an asymptotic nodal surface, Joubert demonstrated recently [Phys. Rev. A 76, 012501 (2007)] strongly anisotropic behavior (in the asymptotic large-r region) of the exact correlation potential of density-functional theory. As is shown by us, this result is a direct and simple consequence of the strong anisotropy of the exact exchange potential obtained by Della Sala and Goerling [Phys. Rev. Lett. 89, 033003 (2002); Della Sala and GoerlingJ. Chem. Phys. 116, 5374 (2002)] and the assumption about the asymptotic isotropy of the Kohn-Sham (KS) potential (based on the investigation of Almbladh and von Barth [Phys. Rev. B 31, 3231 (1985)] for atoms). Joubert's result remains a hypothesis only, because the last assumption is in contradiction with the asymptotic strong anisotropy of the KS potential for systems with asymptotic nodal surface of the HOMO, demonstrated by Wu, Ayers, and Yang [J. Chem. Phys. 119, 2978 (2003)]. The correlation potential in the asymptotic region, stemming from their results, is given

German private mobile telecommunication research program. Effects of a) low-frequency magnetic fields, b) GSM mobile telecommunication signals, c) UMTS signals on the spontaneous leukemia rate of AKR mice

International Nuclear Information System (INIS)

2006-01-01

Since the introduction of private mobile telecommunication about 10 years ago, there is a worldwide discussion about the possible adverse health effects of such highfrequency electromagnetic fields (EMF). Main concerns are regarding the possible cancerogenic or promoting effect of mobile phones and base stations. The insecurity of the public is increased by the continuous development of new techniques and introduction of new systems (e.g. wireless LAN, UMTS), for which insufficient data are available about their possible health hazards. This project's aim was therefore to investigate if chronic exposure to EMF of the UMTS-standard will influence leukaemia or the development of solid tumors in an animal model. The experiment was performed with AKR mice, which is an accepted animal model for leukaemia. With high probability, these mice develop the disease within their lifespan, so that the time course of the onset of leukaemia, bodyweight, blood picture, time of survival, and pathological examinations were the endpoints of the investigation. 160 female AKR/J mice were exposed or sham-exposed for 24 hours per day to EMF of the UMTS-standard (0.4 W/kg SAR). Additionally, 33 animals were kept as cagecontrols. For this experiment special radial waveguides were constructed and built which have a low SAR variability. All experiments were performed in a blinded fashion. The only significant difference between exposed and sham-exposed mice was a higher survival rate of exposed animals. However, the number of ill animals, the mean survival time and the severity code of the disease did not differ between the experimental groups. Animals of the cage-control group had a significant lower growth rate compared to animals kept in the radial waveguides, likely the cause of differences in the method of food supply. The results of this study don't show any negative effects of the exposure. The results do not show any negative effects of exposure for months to EMF at levels 5-fold the

Regulation of IL-17 family members by adrenal hormones during experimental sepsis in mice.

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Bosmann, Markus; Meta, Fabien; Ruemmler, Robert; Haggadone, Mikel D; Sarma, J Vidya; Zetoune, Firas S; Ward, Peter A

2013-04-01

Severe sepsis is a life-threatening disease that causes major morbidity and mortality. Catecholamines and glucocorticoids often have been used for the treatment of sepsis. Several recent studies have suggested a potential role of IL-17 during the development and progression of sepsis in small animal models. In this study, the cross-talk of catecholamines and glucocorticoids with members of the IL-17 family was investigated during sepsis in C57BL/6 mice. The concentrations in plasma of IL-17A, IL-17F, and the IL-17AF heterodimer all were increased greatly in mice after endotoxemia or cecal ligation and puncture as compared with sham mice. Surprisingly, when compared with IL-17A (487 pg/mL), the concentrations of IL-17F (2361 pg/mL) and the heterodimer, IL-17AF (5116 pg/mL), were much higher 12 hours after endotoxemia. After surgical removal of the adrenal glands, mice had much higher mortality after endotoxemia or cecal ligation and puncture. The absence of endogenous adrenal gland hormones (cortical and medullary) was associated with 3- to 10-fold higher concentrations of IL-17A, IL-17F, IL-17AF, and IL-23. The addition of adrenaline, noradrenaline, hydrocortisone, or dexamethasone to lipopolysaccharide-activated peritoneal macrophages dose-dependently suppressed the expression and release of IL-17s. The production of IL-17s required activation of c-Jun-N-terminal kinase, which was antagonized by both catecholamines and glucocorticoids. These data provide novel insights into the molecular mechanisms of immune modulation by catecholamines and glucocorticoids during acute inflammation. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Damage of Inner Ear Sensory Hair Cells via Mitochondrial Loss in a Murine Model of Sleep Apnea With Chronic Intermittent Hypoxia.

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Seo, Young Joon; Ju, Hyun Mi; Lee, Sun Hee; Kwak, Sang Hyun; Kang, Min Jung; Yoon, Joo-Heon; Kim, Chang-Hoon; Cho, Hyung-Ju

2017-09-01

Investigating the exact pathophysiology of obstructive sleep apnea syndrome (OSAS)-induced hearing loss is critical. We sought to verify the hypothesis that a correlation exists between mitochondrial dysfunction in inner ear hair cells and the auditory dysfunction induced by chronic intermittent hypoxia (CIH) in a murine model of sleep apnea. C57BL/6J adult male mice were randomized to 4 weeks of CIH (n = 12) or normoxia (Sham) (n = 12). Hearing threshold was determined by auditory brainstem response. The activity of mitochondria was compared between CIH and Sham mice. Histological assessment and transmission electron microscopy were performed for assessing morphologic changes in mitochondria. The number of mtDNA copies as well as the levels of PGC1-α, Tfam, and VDAC (voltage-dependent anion channel) were determined in the hair cells of CIH mice. We observed that hearing ability in CIH mice was impaired and hair-cell mitochondria in CIH mice were fewer compared to that in Sham and also displayed an aberrant morphology. The mRNA levels of PGC-1α and Tfam were higher in the CIH group than in the Sham group. Moreover, the expression of VDAC was increased in the tectorial membrane, the basilar membrane, and especially in the inner hair cells of CIH mice. This study using CIH mice as a model for OSAS provides evidence of an association between OSAS and auditory function alteration, as well as of mitochondria being part of the pathophysiology of hearing impairment. Further investigation is required to determine whether mitochondria could serve as a valid target for preventive or therapeutic purposes. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Protective effects of a polymethoxy flavonoids-rich Citrus aurantium peel extract on liver fibrosis induced by bile duct ligation in mice.

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Lim, Seol-Wa; Lee, Dong-Ryung; Choi, Bong-Keun; Kim, Hong-Suk; Yang, Seung Hwan; Suh, Joo-Won; Kim, Kyung Soo

2016-12-01

To evaluate the possible protective effect of Citrus aurantium peel extract (CAE) against apoptosis in cholestatic liver fibrosis induced by bile duct ligation in mice. Male ICR mice were divided to 5 groups: 1) Control group (Sham-operated mice), 2) Cholestatic liver injury group induced by bile duct ligation (BDL), 3) BDL mice treated with silymarin (200 mg/kg) for 4 weeks, 4) BDL mice treated with 50 mg/kg CAE for 4 weeks, 5) BDL mice treated with 200 mg/kg CAE for 4 weeks. Mice were sacrificed and liver fibrosis was evaluated by serum and hepatic tissue biochemistry tests and liver histopathological examination. Effects of CAE on inflammation and apoptosis gene regulation were investigated through real-time PCR. CAE effect on lipid metabolism related signaling was determined by western blot analysis. In BDL mice, administration of CAE for 4 weeks markedly attenuated liver fibrosis based on histopathological alteration. Serum and hepatic tissue biochemistry results revealed that CAE (50 and 200 mg/kg) decreased the levels of alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, total bilirubin, nitric oxide, and thiobarbituric acid reactive substances. Real-time PCR and western blot analysis showed that CAE regulated inflammation, apoptosis, and lipid metabolism factors increased by BDL. Interleukin family, tumor necrosis factor α, and related apoptosis factors mRNA levels were increased by BDL treatment. However, these increases were suppressed by CAE administration. In addition, CAE effectively increased phosphorylation of AMP-activated protein kinase, nuclear factor E2-related factor 2, and related cytoprotective proteins. CAE can efficiently regulate BDL-induced liver injury with antioxidant, anti-inflammatory, and anti-apoptotic activities. Copyright © 2016 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Effects of acupuncture on peripheral T lymphocyte subpopulation and amounts of cerebral catecholamines in mice.

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Okumura, M; Toriizuka, K; Iijima, K; Haruyama, K; Ishino, S; Cyong, J C

1999-01-01

The aim of this study was to investigate the effects of acupuncture on peripheral lymphocyte subpopulations and cerebral catecholamines. In order to examine the effects of acupuncture, two experiments were performed. Experiment 1: Eighteen female mice (strain; C57BL/6) at the age of 7 weeks were divided three groups, (a) sham operated (control; n=6), (b) ovariectomized (OVX; n=6), and (c) ovariectomized and stimulated by subcutaneous needles on acupuncture point, Shenshu (BL23) at the both sides of the back for 20 days (OVX+Acu; n=6). These animals were sacrificed at 20 days after needle insertion, and the splenic lymphoid cells were examined by two-color flow cytometry, using monoclonal antibodies (mAb) to the cell surface antigens, CD3, CD4, CD8a and NK1.1 (CD56). In the ovariectomized (OVX) group, the peripheral CD4/CD8 ratio was significantly increased and the ratio of natural killer (NK) cells (CD3-NK1.1+; CD3 negative, NK1.1 positive) to T lymphocytes was decreased compared to the sham control group. In the ovariectomized with needle insertion (OVX+Acu) group, the CD4/CD8 ratio was reduced, but the NK cells ratio was not changed compared to the OVX group. Experiment 2: To investigate the acute effects of subcutaneous needle insertion, male C57BL/6 mice (7 weeks old) were used (n=6, each group). The acupuncture points Shen-shu (BL23) on the backs of the male mice were also stimulated by subcutaneous needles for 3 and 7 days. As a result, the CD4/CD8 ratio was significantly decreased at day 3 and day 7, compared to the control group. On the other hand the NK cells ratio and activated T-cells were increased at day 7. The mitogenic activities in the splenic lymphocytes were also increased by acupuncture stimulation at day 3. Catecholamine contents in the hippocampus were measured by high performance liquid chromatography with the electro-chemical detector (ECD-HPLC) method. No significant change was observed in either dopamine contents or norepinephrine; however

Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation

International Nuclear Information System (INIS)

Yamamoto, Tetsuo; Kinoshita, Manabu; Shinomiya, Nariyoshi; Hiroi, Sadayuki; Sugasawa, Hidekazu; Majima, Takashi; Seki, Shuhji; Matsushita, Yoshitaro; Saitoh, Daizoh

2010-01-01

While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome. (author)

Randomised sham-controlled double-blind multicentre clinical trial to ascertain the effect of percutaneous radiofrequency treatment for lumbar facet joint pain.

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van Tilburg, C W J; Stronks, D L; Groeneweg, J G; Huygen, F J P M

2016-11-01

The aim of this study was to compare the effect of a percutaneous radiofrequency heat lesion at the medial branch of the primary dorsal ramus with a sham procedure, for the treatment of lumbar facet joint pain. A randomised sham-controlled double blind multicentre trial was carried out at the multidisciplinary pain centres of two hospitals. A total of 60 patients aged > 18 years with a history and physical examination suggestive of facet joint pain and a decrease of ≥ 2 on a numerical rating scale (NRS 0 to 10) after a diagnostic facet joint test block were included. In the treatment group, a percutaneous radiofrequency heat lesion (80 o C during 60 seconds per level) was applied to the medial branch of the primary dorsal ramus. In the sham group, the same procedure was undertaken without for the radiofrequency lesion. Both groups also received a graded activity physiotherapy programme. The primary outcome measure was decrease in pain. A secondary outcome measure was the Global Perceived Effect scale (GPE). There was a statistically significant effect on the level of pain in the factor Period (T0-T1). However, there was no statistically significant difference with the passage of time between the groups (Group × Period) or in the factor Group. In the crossover group, 11 of 19 patients had a decrease in NRS of ≥ 2 at one month crossover (p = 0.65). There was no statistically significant difference in satisfaction with the passage of time between the groups (Group × Period). The independent factors Group and Period also showed no statistically significant difference. There was no statistically significant Group × Period effect for recovery, neither an effect of Group or of Period. The null hypothesis of no difference in the decrease in pain and in GPE between the treatment and sham groups cannot be rejected. Post hoc analysis revealed that the age of the patients and the severity of the initial pain significantly predicted a positive outcome. Cite this article

Anti-Inflammatory Effects of Tanshinone IIA on Atherosclerostic Vessels of Ovariectomized ApoE-/- Mice are Mediated by Estrogen Receptor Activation and Through the ERK Signaling Pathway

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Xin Liu

2015-03-01

Full Text Available Aims: Estrogen plays a protective role in atherosclerosis. Our preliminary work demonstrated that the active conformation of Tanshinone IIA(TanIIA is similar to the 17ß-estradiol and it can bind to the estrogen receptor. Here, we hypothesized that Tanshinone IIA might have anti-inflammatory and anti-oxidative effects in atherosclerosis, mediated through estrogen receptor activation. Methods: Subjects for this study were 120 apoE-/- female mice and 20 C57/BL female mice. The apoE-/- mice were ovariectomized (OVX and the C57/BL mice were sham ovariectomized. The sham OVX mice were maintained on a normal diet (NOR group. The OVX apoE-/- mice were fed a high fat diet and randomly divided into 6 groups: Model (MOD group which was fed a high fat diet only, E2 group were given estrogen (E2 0.13mg/kg/d; E2+ICI group were given E2:0.13mg/kg/d and ICI182780:65mg/kg/m; TLD group (TanIIA low dose were given TanIIA: 30mg/kg/d; THD group (TanIIA high dose were given TanIIA:60mg/kg/d; and TLD+ICI group were given TanIIA 30mg/kg/d and ICI182780 65mg/kg/m. After three months of treatment, the aorta and the blood of the mice from each group was collected. The aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE and oil red O staining and for testing the expression of p-ERK1/2 by Western blot. The blood was used for testing the serum cholesterol, superoxide dismutase (SOD, methane dicarboxylic aldehyde (MDA, nuclear factor kappa (NF-κB, soluble intercellular cell adhesion molecule-1 (sICAM-1, activating protein-1 (AP-1, E-selectin and 17ß-estradiol in serum. Results: Tanshinone IIA significantly reduced the lipid deposition in aorta, decreased the levels of total cholesterol (TC, triglyceride (TG, low density lipoprotein (LDL, very low density lipoprotein (VLDL, MDA, NF-κB, sICAM-1, AP-1, and E-selectin in serum but increased the levels of high density lipoprotein (HDL and SOD in serum. Tanshinone IIA also suppressed the

Acute myocardial infarctation in patients with critical ischemia underwent lower limb revascularization

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Esdras Marques Lins

2013-12-01

Full Text Available BACKGROUND: Atherosclerosis is the main cause of peripheral artery occlusive disease (PAOD of the lower limbs. Patients with PAOD often also have obstructive atherosclerosis in other arterial sites, mainly the coronary arteries. This means that patients who undergo infrainguinal bypass to treat critical ischemia have a higher risk of AMI. There are, however, few reports in the literature that have assessed this risk properly. OBJECTIVE: The aim of this study was to determine the incidence of acute myocardial infarction in patients who underwent infrainguinal bypass to treat critical ischemia of the lower limbs caused by PAOD. MATERIAL AND METHODS: A total of 64 patients who underwent 82 infrainguinal bypass operations, from February 2011 to July 2012 were studied. All patients had electrocardiograms and troponin I blood assays during the postoperative period (within 72 hours. RESULTS: There were abnormal ECG findings and elevated blood troponin I levels suggestive of AMI in five (6% of the 82 operations performed. All five had conventional surgery. The incidence of AMI as a proportion of the 52 conventional surgery cases was 9.6%. Two patients died. CONCLUSION: There was a 6% AMI incidence among patients who underwent infrainguinal bypass due to PAOD. Considering only cases operated using conventional surgery, the incidence of AMI was 9.6%.

Pain relief by transcutaneous electric nerve stimulation with bidirectional modulated sine waves in patients with chronic back pain: a randomized, double-blind, sham-controlled study.

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Shimoji, Koki; Takahashi, Norio; Nishio, Yasuyuki; Koyanagi, Mika; Aida, Sumihisa

2007-01-01

Objectives.  Newly developed bidirectional modulated sine waves (BMW) might provide some derived benefit to patients with low back pain. Pain relief by transcutaneous electric nerve stimulation (TENS) with BMWs was tested. Materials and Methods.  Analgesic effects of BMWs and conventional bidirectional pulsed waves on chronic back pain in 28 patients were compared, and effects of repeated TENS using BMWs on chronic back pain were investigated in 21 patients by means of a randomized double-blind, sham-controlled, parallel-group method. Pain intensity was assessed using numerical rating scale (NRS). Results.  There was significant immediate reduction in NRS in patients receiving BMWs, and 60 min after treatment compared to sham TENS. Weekly repeated treatments using massage and TENS with BMWs for 5 weeks resulted in a decrease of NRS, but there were no significant differences between the TENS plus massage and sham TENS plus massage groups. Conclusions.  This study shows that TENS with BMWs significantly inhibits chronic back pain, and treatment effects are attained within a day. The results also suggest that there were no statistically significant long-term effects of TENS with BMW in the repeated treatment.

Mice Lacking the β2 Adrenergic Receptor Have a Unique Genetic Profile before and after Focal Brain Ischaemia

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Robin E White

2012-08-01

Full Text Available The role of the β2AR (β2 adrenergic receptor after stroke is unclear as pharmacological manipulations of the β2AR have produced contradictory results. We previously showed that mice deficient in the β2AR (β2KO had smaller infarcts compared with WT (wild-type mice (FVB after MCAO (middle cerebral artery occlusion, a model of stroke. To elucidate mechanisms of this neuroprotection, we evaluated changes in gene expression using microarrays comparing differences before and after MCAO, and differences between genotypes. Genes associated with inflammation and cell deaths were enriched after MCAO in both genotypes, and we identified several genes not previously shown to increase following ischaemia (Ccl9, Gem and Prg4. In addition to networks that were similar between genotypes, one network with a central core of GPCR (G-protein-coupled receptor and including biological functions such as carbohydrate metabolism, small molecule biochemistry and inflammation was identified in FVB mice but not in β2KO mice. Analysis of differences between genotypes revealed 11 genes differentially expressed by genotype both before and after ischaemia. We demonstrate greater Glo1 protein levels and lower Pmaip/Noxa mRNA levels in β2KO mice in both sham and MCAO conditions. As both genes are implicated in NF-κB (nuclear factor κB signalling, we measured p65 activity and TNFα (tumour necrosis factor α levels 24 h after MCAO. MCAO-induced p65 activation and post-ischaemic TNFα production were both greater in FVB compared with β2KO mice. These results suggest that loss of β2AR signaling results in a neuroprotective phenotype in part due to decreased NF-κB signalling, decreased inflammation and decreased apoptotic signalling in the brain.

Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma A Multicenter, Randomized, Double-Blind, Sham-Controlled Clinical Trial

NARCIS (Netherlands)

Castro, Mario; Rubin, Adalberto S.; Laviolette, Michel; Fiterman, Jussara; Lima, Marina De Andrade; Shah, Pallav L.; Fiss, Elie; Olivenstein, Ronald; Thomson, Neil C.; Niven, Robert M.; Pavord, Ian D.; Simoff, Michael; Duhamel, David R.; McEvoy, Charlene; Barbers, Richard; ten Hacken, Nicolaas H. T.; Wechsler, Michael E.; Holmes, Mark; Phillips, Martin J.; Erzurum, Serpil; Lunn, William; Israel, Elliot; Jariour, Nizar; Kraft, Monica; Shargill, Narinder S.; Quiring, John; Berry, Scott M.; Cox, Gerard

2010-01-01

Rationale Bronchial thermoplasty (BT) is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle. Objectives: To evaluate the effectiveness and safety of BT versus a sham procedure in subjects with severe asthma who remain symptomatic

Effect of bite-raised condition on the hippocampal cholinergic system of aged SAMP8 mice.

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Katayama, Tasuku; Mori, Daisuke; Miyake, Hidekazu; Fujiwara, Shuu; Ono, Yumie; Takahashi, Toru; Onozuka, Minoru; Kubo, Kin-Ya

2012-06-27

Occlusal disharmony induces chronic stress, which results in learning deficits in association with the morphologic changes in the hippocampus, e.g., neuronal degeneration and increased hypertrophied glial fibrillary acidic protein-positive cells. To investigate the mechanisms underlying impaired hippocampal function resulting from occlusal disharmony, we examined the effects of the bite-raised condition on the septohippocampal cholinergic system by assessing acetylcholine release in the hippocampus and choline acetyltransferase immunoreactivity in the medial septal nucleus in aged SAMP8 mice that underwent the bite raising procedure. Aged bite-raised mice showed decreased acetylcholine release in the hippocampus and a reduced number of choline acetyltransferase-immunopositive neurons in the medial septal nucleus compared to age-matched control mice. These findings suggest that the bite-raised condition in aged SAMP8 mice enhances the age-related decline in the septohippocampal cholinergic system, leading to impaired learning. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Late-occurring chromosome aberrations and global DNA methylation in hematopoietic stem/progenitor cells of CBA/CaJ mice exposed to silicon ({sup 28}Si) ions

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Rithidech, Kanokporn Noy, E-mail: kanokporn.rithidech@stonybrookmedicine.edu [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Honikel, Louise M. [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Reungpathanaphong, Paiboon [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Department of Applied Radiation and Isotopes, Faculty of Sciences, Kasetsart University, Chatuchuck, Bangkok 10900 (Thailand); Tungjai, Montree [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Department of Radiologic Technology, Faculty of Associated Medical Sciences, Center of Excellence for Molecular Imaging, Chiang Mai University, Chiang Mai 50200 (Thailand); Jangiam, Witawat [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Department of Chemical Engineering, Faculty of Engineering, Burapha University, Chonburi 20131 (Thailand); Whorton, Elbert B. [StatCom, PO Box 3041, Galveston, TX 77551 (United States)

2015-11-15

Highlights: • Late-occurring chromosome aberrations were found in HSPCs of exposed CBA/CaJ mice. • A dose-dependent reduction in the level of global 5hmC was detected in HSPCs. • There is a link between reduced global 5hmC levels and genomic instability in vivo. • The level of global 5hmC is a better marker of radiation exposure than that of 5mC. - Abstract: Although myeloid leukemia (ML) is one of the major health concerns from exposure to space radiation, the risk prediction for developing ML is unsatisfactory. To increase the reliability of predicting ML risk, a much improved understanding of space radiation-induced changes in the target cells, i.e. hematopoietic stem/progenitor cells (HSPCs), is important. We focused on the in vivo induction of late-occurring damage in HSPCs of mice exposed to {sup 28}Si ions since such damage is associated with radiation-induced genomic instability (a key event of carcinogenesis). We gave adult male CBA/CaJ mice, known to be sensitive to radiation-induced ML, a whole-body exposure (2 fractionated exposures, 15 days apart, that totaled each selected dose, delivered at the dose-rate of 1 cGy/min) to various doses of 300 MeV/n {sup 28}Si ions, i.e. 0 (sham controls), 0.1, 0.25, or 0.5 Gy. At 6 months post-irradiation, we collected bone marrow cells from each mouse (five mice per treatment-group) for obtaining the myeloid-lineage of HSPC-derived clones for analyses. We measured the frequencies of late-occurring chromosome aberrations (CAs), using the genome-wide multicolor fluorescence in situ hybridization method. The measurement of CAs was coupled with the characterization of the global DNA methylation patterns, i.e. 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). A dose-dependent increase in the frequencies of CAs was detected (Analysis of Variance or ANOVA, p < 0.01), indicating the induction of genomic instability after exposure of mice to 300 MeV/n {sup 28}Si ions. Slight increases in the levels of 5m

The influence of stachydrine hydrochloride on the reperfusion model of mice with repetitive cerebral ischemia

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Mingsan Miao

2017-03-01

Full Text Available To study the influence of stachydrine hydrochloride on the inflammatory cytokines and tissue morphology of the re-perfusion model of mice with repetitive cerebral ischemia and probe into the protection mechanism of stachydrine hydrochloride for cerebral ischemia reperfusion impairment. Build a repetitive cerebral ischemia reperfusion model by first blocking the common carotid artery on both sides for 10 min, then resuming perfusion for 10 min and then blocking the common carotid artery on both sides again for 10 min. Before the operation, all the mice in the Nimodipine group, and the big, medium and small stachydrine hydrochloride dose groups were given corresponding gastric perfusion, the mice in the sham operation group and the modeled groups were at the same time given 0.5% sodium carboxymethyl cellulose for gastric perfusion of the same volume. The medicine was fed daily for 7 consecutive days. The model was built 1 h after the last feed and the perfusion continued for 24 h after the operation. Then the death rate of the mice was calculated. The mouse brains were taken out to test the ICAM-1 level and the TNF-α level, and the serum was taken out to test the NSE level and the MPO level. The tissue morphology changes were also observed. All the repetitive cerebral ischemia reperfusion models were successfully duplicated. The stachydrine hydrochloride in all the dose groups significantly reduced the death rates of big and small mice, reduced the level of ICAM-1 and the level of TNF-α in the brain tissues and the NSE level and the MPO level in the serum, significantly alleviating the pathological impairment in the hippocampus. Stachydrine hydrochloride can significantly reduce the death rate of mice, improve the pathological changes in the hippocampus, inhibit inflammatory reactions after ischemia, thus reducing the re-perfusion impairment after cerebral ischemia.

Tau reduction diminishes spatial learning and memory deficits after mild repetitive traumatic brain injury in mice.

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Jason S Cheng

Full Text Available OBJECTIVE: Because reduction of the microtubule-associated protein Tau has beneficial effects in mouse models of Alzheimer's disease and epilepsy, we wanted to determine whether this strategy can also improve the outcome of mild traumatic brain injury (TBI. METHODS: We adapted a mild frontal impact model of TBI for wildtype C57Bl/6J mice and characterized the behavioral deficits it causes in these animals. The Barnes maze, Y maze, contextual and cued fear conditioning, elevated plus maze, open field, balance beam, and forced swim test were used to assess different behavioral functions. Magnetic resonance imaging (MRI, 7 Tesla and histological analysis of brain sections were used to look for neuropathological alterations. We also compared the functional effects of this TBI model and of controlled cortical impact in mice with two, one or no Tau alleles. RESULTS: Repeated (2-hit, but not single (1-hit, mild frontal impact impaired spatial learning and memory in wildtype mice as determined by testing of mice in the Barnes maze one month after the injury. Locomotor activity, anxiety, depression and fear related behaviors did not differ between injured and sham-injured mice. MRI imaging did not reveal focal injury or mass lesions shortly after the injury. Complete ablation or partial reduction of tau prevented deficits in spatial learning and memory after repeated mild frontal impact. Complete tau ablation also showed a trend towards protection after a single controlled cortical impact. Complete or partial reduction of tau also reduced the level of axonopathy in the corpus callosum after repeated mild frontal impact. INTERPRETATION: Tau promotes or enables the development of learning and memory deficits and of axonopathy after mild TBI, and tau reduction counteracts these adverse effects.

Cigarette smoke exposure promotes arterial thrombosis and vessel remodeling after vascular injury in apolipoprotein E-deficient mice.