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Distribution by Scientific Domains

Medical Sciences	53%
Life Sciences	46%

Selected Abstracts

RANKL Inhibition with Osteoprotegerin Increases Bone Strength by Improving Cortical and Trabecular bone Architecture in Ovariectomized Rats,,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008
Michael S Ominsky
Abstract Introduction: Ovariectomy (OVX) results in bone loss caused by increased bone resorption. RANKL is an essential mediator of bone resorption. We examined whether the RANKL inhibitor osteoprotegerin (OPG) would preserve bone volume, density, and strength in OVX rats. Materials and Methods: Rats were OVX or sham-operated at 3 mo of age. Sham controls were treated for 6 wk with vehicle (Veh, PBS). OVX rats were treated with Veh or human OPG-Fc (10 mg/kg, 2/wk). Serum RANKL and TRACP5b was measured by ELISA. BMD of lumbar vertebrae (L1,L5) and distal femur was measured by DXA. Right distal femurs were processed for bone histomorphometry. Left femurs and the fifth lumbar vertebra (L5) were analyzed by ,CT and biomechanical testing, and L6 was analyzed for ash weight. Results: OVX was associated with significantly greater serum RANKL and osteoclast surface and with reduced areal and volumetric BMD. OPG markedly reduced osteoclast surface and serum TRACP5b while completely preventing OVX-associated bone loss in the lumbar vertebrae, distal femur, and femur neck. Vertebrae from OPG-treated rats had increased dry and ash weight, with no significant differences in tissue mineralization versus OVX controls. ,CT showed that trabecular compartments in OVX-OPG rats had significantly greater bone volume fraction, vBMD, bone area, trabecular thickness, and number, whereas their cortical compartments had significantly greater bone area (p < 0.05 versus OVX-Veh). OPG improved cortical area in L5 and the femur neck to levels that were significantly greater than OVX or sham controls (p < 0.05). Biomechanical testing of L5 and femur necks showed significantly greater maximum load values in the OVX-OPG group (p < 0.05 versus OVX-Veh). Bone strength at both sites was linearly correlated with total bone area (r2 = 0.54,0.74, p < 0.0001), which was also significantly increased by OPG (p < 0.05 versus OVX). Conclusions: OPG treatment prevented bone loss, preserved trabecular architecture, and increased cortical area and bone strength in OVX rats. [source]

Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats

JOURNAL OF PINEAL RESEARCH, Issue 4 2008
Supriti Samantaray
Abstract:, Multiple investigations in vivo have shown that melatonin (MEL) has a neuroprotective effect in the treatment of spinal cord injury (SCI). This study investigates the role of MEL as an intervening agent for ameliorating Ca2+ -mediated events, including activation of calpain, following its administration to rats sustaining experimental SCI. Calpain, a Ca2+ -dependent neutral protease, is known to be involved in the pathogenesis of SCI. Rats were injured using a standard weight-drop method that induced a moderately severe injury (40 g.cm force) at T10. Sham controls received laminectomy only. Injured animals were given either 45 mg/kg MEL or vehicle at 15 min post-injury by intraperitoneal injection. At 48 hr post-injury, spinal cord (SC) samples were collected. Immunofluorescent labelings were used to identify calpain expression in specific cell types, such as neurons, glia, or macrophages. Combination of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and double immunofluorescent labelings was used to identify apoptosis in specific cells in the SC. The effect of MEL on axonal damage was also investigated using antibody specific for dephosphorylated neurofilament protein (dNFP). Treatment of SCI animals with MEL attenuated calpain expression, inflammation, axonal damage (dNFP), and neuronal death, indicating that MEL provided neuroprotective effect in SCI. Further, expression and activity of calpain and caspse-3 were examined by Western blotting. The results indicated a significant decrease in expression and activity of calpain and caspse-3 in SCI animals after treatment with MEL. Taken together, this study strongly suggested that MEL could be an effective neuroprotective agent for treatment of SCI. [source]

An in ovo chicken model to study the systemic and localized teratogenic effects of valproic acid

BIRTH DEFECTS RESEARCH, Issue 4 2002
Amy I. Whitsel
Background The antiepileptic valproic acid (VPA) is a teratogen whose embryopathic mechanism(s) remain uncertain. Elucidating potential cellular and molecular effects of VPA is complicated by systemic application paradigms. We developed an in ovo model to reproduce the teratogenic effects of VPA and a localized VPA application procedure to determine whether VPA can selectively effect abnormal development in one region of the embryo. Methods VPA was applied topically to chicken embryos in ovo at different embryonic stages. Embryos were later evaluated for gross and skeletal anomalies. Pax-2 and Pax-6 protein expression in the developing eye was also evaluated because VPA-induced eye anomalies are similar to those seen by the disruption of Pax-2 and Pax-6. For localized application, a thin sheet of the synthetic polymer Elvax was impregnated with VPA. A small piece of the VPA-impregnated polymer was applied directly to the presumptive wing bud region in Stage 10,17 embryos. Embryos were examined for gross and skeletal anomalies. Sham controls were employed for all experiments. Results Chicken embryos exposed to VPA in ovo demonstrated increased mortality, growth delay and anomalies similar to ones previously seen in humans: neural tube, cardiovascular, craniofacial, limb and skeletal. Pax-2 and Pax-6 protein expression was qualitatively diminished in the eye. Localized wing bud VPA exposure caused structural abnormalities in the developing wing in the absence of other anomalies in the embryos. These wing defects were similar to those observed after topical whole-embryo VPA application. Conclusions These results indicate that at least one mechanism for the teratogenicity of VPA involves a direct effect on developing tissue. The nature of the abnormalities observed implies that this effect may be mediated by disruption of genes that regulate pattern formation. Teratology 66:153,163, 2002. © 2002 Wiley-Liss, Inc. [source]

Overload-induced skeletal muscle extracellular matrix remodelling and myofibre growth in mice lacking IL-6

ACTA PHYSIOLOGICA, Issue 4 2009
J. P. White
Abstract Aim:, Overloading healthy skeletal muscle produces myofibre hypertrophy and extracellular matrix remodelling, and these processes are thought to be interdependent for producing muscle growth. Inflammatory cytokine interleukin-6 (IL-6) gene expression is induced in overloaded skeletal muscle, and the loss of this IL-6 induction can attenuate the hypertrophic response to overload (OV). Although the OV induction of IL-6 in skeletal muscle may be an important regulator of inflammatory processes and satellite cell proliferation, less is known about its role in the regulation of extracellular matrix remodelling. The purpose of the current study was to examine if OV-induced extracellular matrix remodelling, muscle growth, and associated gene expression were altered in mice that lack IL-6, when compared with wild-type mice. Methods:, Male C57/BL6 (WT) and C57/BL6 × IL-6,/, (IL-6,/,) mice (10 weeks of age) were assigned to either a sham control or synergist ablation OV treatments for 3, 21 or 56 days. Result:, Plantaris muscle mass increased 59% in WT and 116% in IL-6,/, mice after 21 day OV. Myofibre CSA was also increased by 21 day OV in both WT and IL-6,/, mice. OV induced a twofold greater increase in the volume of non-contractile tissue in IL-6,/, muscle compared to WT. OV also induced a significantly greater accumulation of hydroxyproline and procollagen-1 mRNA in IL-6,/, muscle, when compared with WT muscle after 21 day OV. Transforming growth factor-, and insulin-like growth factor-1 mRNA expression were also induced to a greater extent in IL-6,/, muscle when compared with WT muscle after 21 day OV. There was no effect of IL-6 loss on the induction of myogenin, and cyclin D1 mRNA expression after 3 day OV. However, MyoD mRNA expression in 3 day OV IL-6,/, muscle was attenuated when compared with WT OV mice. Conclusion:, IL-6 appears to be necessary for the normal regulation of extracellular matrix remodelling during OV-induced growth. [source]

Non-penetrating sham needle , is it an adequate sham control for acupuncture research in Korean people?

FOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 2006
HS Lee
[source]

Acute Ethanol Exposure Combined With Burn Injury Enhances IL-6 Levels in the Murine Ileum

ALCOHOLISM, Issue 10 2007
Michael T. Scalfani
Background:, Recent studies suggest that ethanol use imposes a greater risk of trauma-associated intestinal injury than trauma alone. The initiating and regulatory factors for multiple organ dysfunction syndromes are not well defined, yet evidence points to the gut as a possible trigger of the systemic inflammatory cascade as well as a potential source of cytokines. In the current study, we hypothesized that ethanol administration would alter cytokine levels and intestinal infiltration by neutrophils within the ileum of mice exposed to burn injury (15% total body surface of dorsal skin). Methods:, Ileal samples were collected for histological assessment, myeloperoxidase quantitation and the protein presence of tumor necrosis factor alpha (TNF,), interleukin (IL-) 6, macrophage inflammatory protein-2 (MIP-2; CXCL2) and the anti-inflammatory cytokine, IL-10. Additional ileal tissue samples were examined for localization of the IL-6 immunoreactivity. Results:, We did not detect statistically significant cytokine/chemokine differences (MIP-2 and IL-10) between sham control and treatment conditions at either 2 or 24 hours. However, there was a significant decrease in TNF, at 24 hours in both burn injury alone and in combination with ethanol treatment conditions (p < 0.05). In addition, there was an increase in IL-6 levels at 24 hours in intestinal tissue obtained from mice subjected to a combination of acute ethanol and burn injury, compared to the mice receiving burn or sham injury (p < 0.001). Ileal homogenate increases in IL-6 at 24 hours were concurrent with decreased villus height in the ileum, but no discernable changes in neutrophil infiltration (myeloperoxidase activity levels) at either 2 or 24 hours. Additional immunocytochemical localization studies of ileal tissue revealed that there was a substantial increase of IL-6 in intestinal enterocytes subjected to both burn injury alone, or in combination with acute ethanol exposure. Conclusions:, The present study suggests that acute ethanol exposure combined with burn injury enhances levels of IL-6 protein in the ileum. The enhanced levels of ileal IL-6 are likely due to enterocyte production of the cytokine. [source]

Nuclear factor-,B inhibition improves myocardial contractility in rats with cirrhotic cardiomyopathy

LIVER INTERNATIONAL, Issue 5 2008
Hongqun Liu
Abstract Background/Aims: Cytokines such as tumour necrosis factor (TNF-,) contribute to the pathogenesis of cirrhotic cardiomyopathy. Nuclear factor-,B (NF-,B) is crucial for cytokine regulation, and induces cardiac dysfunction in several heart disease models. We aimed to elucidate possible NF-,B involvement in cirrhotic cardiomyopathy. Methods: Rats were bile duct ligated (BDL) to produce cirrhosis; controls received sham operation. Animals were studied 4 weeks later. Two NF-,B inhibitors were used: pyrrolidine dithiocarbamate (PDTC) and Bay 11-7082. Four groups were studied in most protocols: sham control, sham+PDTC, BDL and BDL+PDTC. Additional contractility studies were performed with Bay 11-7082. Myocardial NF-,B and TNF-, expression was measured by Western blot and ELISA. The contractility of isolated cardiomyocytes was observed under direct microscopy. Results: Nuclear factor-,B and TNF-, levels were increased in cirrhotic hearts compared with controls. PDTC significantly reduced NF-,B activity and TNF-, expression in cirrhotic hearts; controls were unaffected. Cirrhotic cardiomyocytes showed decreased systolic and diatolic velocity compared with sham controls. Both PDTC and Bay 11-7082 restored contractile function in cirrhotic cardiomyocytes, but did not affect controls. Conclusions: Inhibition of the increased NF-,B activity in cirrhotic hearts was associated with improvement of attenuated cardiomyocyte contractility. NF-,B, via effects on cytokine expression, may contribute to the pathogenesis of cirrhotic cardiomyopathy. [source]

Influence of exposure to electromagnetic field on the cardiovascular system

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2005
J. H. Jeong
Summary 1 We examined whether extremely low frequency electromagnetic fields (ELF-EMF) affect the basal level of cardiovascular parameters and influence of drugs acting on the sympathetic nervous system. 2 Male rats were exposed to sham control and EMF (60 Hz, 20 G) for 1 (MF-1) or 5 days (MF-5). We evaluated the alterations of blood pressure (BP), pulse pressure (PP), heart rate (HR), and the PR interval, QRS interval and QT interval on the electrocardiogram and dysrhythmic ratio in basal level and dysrhythmia induced by , -adrenoceptor agonists. 3 In terms of the basal levels, there were no statistically significant differences among control, MF-1 and MF-5 in PR interval, QRS interval, mean BP, HR and PP. However, the QT interval, representing ventricular repolarization, was significantly reduced by MF-1 (P < 0.05). 4 (,)-Dobutamine (,1 -adrenoceptor-selective agonist)-induced tachycardia was significantly suppressed by ELF-EMF exposure in MF-1 for the increase in HR (,HR), the decrease in QRS interval (,QRS) and the decrease in QT (,QT) interval. Adrenaline (nonselective , -receptor agonist)-induced dysrhythmia was also significantly suppressed by ELF-EMF in MF-1 for the number of missing beats, the dysrhythmic ratio, and the increase in BP and PP. 5 These results indicated that 1-day exposure to ELF-EMF (60 Hz, 20 G) could suppress the increase in HR by affecting ventricular repolarization and may have a down-regulatory effect on responses of the cardiovascular system induced by sympathetic agonists. [source]

No effect of TETRA hand portable transmission signals on human cognitive function and symptoms

BIOELECTROMAGNETICS, Issue 5 2010
Ingunn S. Riddervold
Abstract Current radio frequency radiation exposure guidelines rest on well-established thermal effects. However, recent research into analogue and digital transmission fields at levels covered by the exposure guidelines has indicated possible detrimental effects on human cognitive performance. To investigate this, we conducted a controlled climate chamber study of possible changes in cognitive performance in healthy volunteers exposed to transmission signals from TETRA hand portables (TETRA handsets). The trial deployed a balanced, randomized, double-blinded cross-over design. Performance on different paper-and-pencil, auditory and computer-based cognitive tasks was monitored in 53 male volunteers (mean age 36.41 years, SD 8.35) during 45-min exposure to a TETRA handset and sham control signals remotely controlled from a laboratory more than 100,km away. The main cognitive outcome was the Trail Making B (TMB) test. In addition, the participants completed a computer-based questionnaire measuring self-reported psychological and physical symptoms. No statistically significant differences (P,<,0.05) between the TETRA and sham conditions were found for either TMB (estimated difference 3.8%, confidence interval (CI) ,1.6% to 9.2%) or any of the remaining cognitive tasks or symptoms. In conclusion, we found no evidence that brief exposure to hand-held TETRA transmitters' affects human cognitive function or subjective symptoms. Bioelectromagnetics 31:380,390, 2010. © 2010 Wiley-Liss, Inc. [source]

Lack of a co-promotion effect of 60,Hz circularly polarized magnetic fields on spontaneous development of lymphoma in AKR mice

BIOELECTROMAGNETICS, Issue 2 2010
Moon-Koo Chung
Abstract The present study was conducted to investigate the possible effect of 60,Hz circularly polarized magnetic fields (MFs) as promoters of genetically initiated lymphoma in AKR mice. One hundred sixty female animals were divided into four different groups. They were exposed to four different intensities of circularly polarized MFs. Animals received exposure to 60,Hz circularly polarized MF at field strengths (rms-value) of 0,µT (sham control, T1, Group I), 5,µT(T2, Group II), 83.3,µT (T3, Group III), or 500,µT(T4, Group IV), for 21,h/day from the age of 4,6 weeks to the age of 44,46 weeks. There were no exposure-related changes in mean survival time, clinical signs, body weights, hematological values, micronucleus assay, gene expression arrays, analysis of apoptosis, and necropsy findings. At histopathological examination, lymphoma was seen in all the groups. The tumor incidence was 31/40(78%), 30/40(75%), 32/40(80%), and 31/40(78%) in sham control, 5, 83.3, and 500,µT groups, respectively. However, there were no differences in the tumor incidence between the sham control (T1) and circularly polarized MF exposure groups (T2,T4). In conclusion, there was no evidence that exposure to 60,Hz circularly polarized MF strengths up to 500,µT promoted lymphoma in AKR mice. Bioelectromagnetics 31:130,139, 2010. © 2009 Wiley-Liss, Inc. [source]

Effect of millimeter wave irradiation on tumor metastasis

BIOELECTROMAGNETICS, Issue 4 2006
Mahendra K. Logani
Abstract One of the major side effects of chemotherapy in cancer treatment is that it can enhance tumor metastasis due to suppression of natural killer (NK) cell activity. The present study was undertaken to examine whether millimeter electromagnetic waves (MMWs) irradiation (42.2 GHz) can inhibit tumor metastasis enhanced by cyclophosphamide (CPA), an anticancer drug. MMWs were produced with a Russian-made YAV-1 generator. Peak SAR and incident power density were measured as 730,±,100 W/kg and 36.5,±,5 mW/cm2, respectively. Tumor metastasis was evaluated in C57BL/6 mice, an experimental murine model commonly used for metastatic melanoma. The animals were divided into 5 groups, 10 animals per group. The first group was not given any treatment. The second group was irradiated on the nasal area with MMWs for 30 min. The third group served as a sham control for group 2. The fourth group was given CPA (150 mg/kg body weight, ip) before irradiation. The fifth group served as a sham control for group 4. On day 2, all animals were injected, through a tail vein, with B16F10 melanoma cells, a tumor cell line syngeneic to C57BL/6 mice. Tumor colonies in lungs were counted 2 weeks following inoculation. CPA caused a marked enhancement in tumor metastases (fivefold), which was significantly reduced when CPA-treated animals were irradiated with MMWs. Millimeter waves also increased NK cell activity suppressed by CPA, suggesting that a reduction in tumor metastasis by MMWs is mediated through activation of NK cells. Bioelectromagnetics 27:258,264, 2006. © 2006 Wiley-Liss, Inc. [source]

Lack of adverse effects in pregnant/lactating female rats and their offspring following pre- and postnatal exposure to ELF magnetic fields

BIOELECTROMAGNETICS, Issue 4 2004
Moon-Koo Chung
Abstract We have recently reported that exposure of pregnant rats to 60 Hz at field strengths up to 0.5 mT during the entire period of pregnancy did not induce any biologically significant effects on both pregnant dams and embryo-fetal development. The present study was carried out to investigate the potential effects of gestational and lactational MF exposure on pregnancy, delivery, and lactation of dams and growth, behavior, and mating performance of their offspring in rats. Timed-pregnant female Sprague,Dawley (SD) rats (24/group) received continuous exposure to 60 Hz magnetic field (MF) at field strengths of 0 (sham control), 5 ,T, 83.3 ,T, or 0.5 mT. Dams received MF or sham exposures for 21 h/day from gestational day 6 through lactational day 21. Experimentally generated MF was monitored continuously throughout the study. No exposure-related changes in clinical signs, body weight, food consumption, pregnancy length, and necropsy findings were observed in dams. Parameters of growth, behavior, and reproductive performance of offspring showed no changes related to MF exposure. There were no adverse effects on embryo-fetal development of F2 offspring from dams exposed to MF. In conclusion, exposure of pregnant SD rats to 60 Hz at field strengths up to 0.5 mT from gestational day 6 to lactational day 21 did not produce biologically significant effects in dams, F1 offspring, or F2 fetuses. Bioelectromagnetics 25:236,244, 2004. © 2004 Wiley-Liss, Inc. [source]

Developmental toxicity evaluation of ELF magnetic fields in Sprague,Dawley rats

BIOELECTROMAGNETICS, Issue 4 2003
Moon-Koo Chung
Abstract To identify possible effects of horizontally polarized magnetic field (MF) exposure on maintenance of pregnancy and embryo-fetal development, an MF exposure system was designed and constructed and 96 time-mated female Sprague,Dawley (SD) rats (24/group) received continuous exposure to 60 Hz MF at field strengths of 0 (sham control) and 5, 83.3, or 500 ,T (50, 833, or 5000 mG). Dams received MF or sham exposures for 22 h/day on gestational day 6,20. MF was monitored continuously throughout the study. There were no evidences of maternal toxicity or developmental toxicity in any MF exposed groups. Mean maternal body weight, organ weights, and hematological and serum biochemical parameters in groups exposed to MF did not differ from those in sham control. No exposure related differences in fetal deaths, fetal body weight, and placental weight were observed between MF exposed groups and sham control. External, visceral, and skeletal examination of fetuses demonstrated no significant differences in the incidence of fetal malformations between MF exposed and sham control groups. In conclusion, exposure of pregnant rats to 60 Hz at MF strengths up to 500 ,T during gestation day 6,20 did not produce any biologically significant effect in either dams or fetuses. Bioelectromagnetics 24:231-240, 2003. © 2003 Wiley-Liss, Inc. [source]

The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation

BJU INTERNATIONAL, Issue 9 2002
A.M. Freitas
Objective,To evaluate the effect of an aqueous extract of Phyllanthus niruri (Pn), a plant used in folk medicine to treat lithiasis, on the urinary excretion of endogenous inhibitors of lithogenesis, citrate, magnesium and glycosaminoglycans (GAGs). Materials and methods,The effect of chronic (42 days) administration of Pn (1.25 mg/mL/day, orally) was evaluated in a rat model of urolithiasis induced by the introduction of a calcium oxalate (CaOx) seed into the bladder of adult male Wistar rats. The animals were divided into four groups: a sham control (16 rats); a control+Pn (six); CaOx+water instead of Pn (14); and CaOx+Pn (22). Plasma and urine were collected after 42 days of treatment for biochemical analysis and the determination of urinary excretion of citrate, magnesium and GAGs. The animals were then killed and the calculi analysed. Results,The creatinine clearance or urinary and plasma concentrations of Na+, K+, Ca2+, oxalate, phosphate and uric acid were unaffected by Pn or the induction of lithiasis. Treatment with Pn strongly inhibited the growth of the matrix calculus and reduced the number of stone satellites compared with the group receiving water. The calculi were eliminated or dissolved in some treated animals (three of 22). The urinary excretion of citrate and magnesium was unaffected by Pn treatment. However, the mean (sd) urinary concentration of GAGs was significantly lower in rats treated with CaOx+Pn, at 5.64 (0.86) mg/g creatinine, than when treated with CaOx + water, at 11.78 (2.21) mg/g creatinine. In contrast, the content of GAGs in the calculi was higher in the CaOx + Pn rats, at 48.0 (10.4) g/g calculus, than in the CaOx + water group, at 16.6 (9.6) g/g calculus. Conclusion,These results show that Pn has an inhibitory effect on crystal growth, which is independent of changes in the urinary excretion of citrate and Mg, but might be related to the higher incorporation of GAGs into the calculi. [source]

Gastroduodenal reflux induces group IIa secretory phospholipase A2 expression and activity in murine esophagus

DISEASES OF THE ESOPHAGUS, Issue 5 2010
David Mauchley
SUMMARY Exposure of esophageal epithelium to gastric and duodenal contents results in the histologic changes of hyperproliferation and mucosal thickening. We have previously shown that presence of secretory phospholipase A2 (sPLA2) is necessary to produce these histologic changes in a murine model of gastroduodenal reflux. We sought to determine the influence of gastroduodenal reflux (GDR) on sPLA2 protein and mRNA levels as well as enzyme activity in esophageal tissue. BALB/c (sPLA2+/+) mice (n= 28) underwent side-to-side surgical anastomosis of the first portion of the duodenum and GE junction (DGEA) resulting in continuous exposure of esophageal mucosa to mixed gastric and duodenal contents. Sham control mice (n= 14) underwent laparotomy, esophagotomy and closure. Real-time RT PCR was used to quantitate the influence of GDR on group IIa sPLA2 expression. Immunofluorescent staining was quantitated by digital microscopy using a specific antibody to identify and locate sPLA2 protein. A colorimetric assay was used to quantify total sPLA2 activity after standardization of protein levels. Statistical analysis was conducted using Student's t -test. Group IIa sPLA2 mRNA and protein levels were increased at 4 and 8 weeks compared with sham controls. This increase occurred in a time-dependent manner and correlated with esophageal mucosal thickness. Furthermore, sPLA2 enzyme activity was increased significantly at 4 and 8 weeks compared with untreated controls. The expression of group IIa sPLA2 as well as sPLA2 activity is induced by GDR. This novel finding indicates that sPLA2 may play a role in the development of the histologic changes produced by GDR in esophageal mucosa. [source]

Kindling Limits the Interictal Neuronal Temporal Response Properties in Cat Primary Auditory Cortex

EPILEPSIA, Issue 2 2005
Pamela A. Valentine
Summary:,Purpose: The present study examined the effect of electrical kindling on the interictal temporal response properties of single units recorded from primary auditory cortex (AI) of the adult cat. Methods: Cats were permanently implanted with electrodes in AI, kindled twice daily for 40 sessions, and the contralateral AI was subsequently mapped. Kindling stimulation consisted of 1-s trains of biphasic square-wave pulses applied at a frequency of 60 Hz, 100 ,A above the afterdischarge (AD) threshold. The EEG activity was recorded during each kindling session, and the behavioral manifestation was scored. Subsequent to kindling, multiple single-unit responses were recorded under ketamine anesthesia in response to 1-s-long periodic click trains, with click rates between 2 and 64 Hz. Neuronal responses were characterized according to their ability to respond in time-locked fashion to the clicks. Results: Kindling stimulation resulted in progression of the AD characteristics and seizure behavior, with six of 10 kindled cats reaching a fully generalized state. In the fully kindled cats, the best modulation frequencies and limiting following rates for the single-unit responses were significantly lower compared with those of naive and sham controls. Conclusions: Repeated epileptiform activity interferes with temporal processing in cat auditory cortex in the interictal state. This may have implications for people with epileptic foci in auditory-related areas. [source]

Chemokine expression in the white matter spinal cord precursor niche after force-defined spinal cord contusion injuries in adult rats

GLIA, Issue 8 2010
Friederike Knerlich-Lukoschus
Abstract Inflammatory cascades induced by spinal cord injuries (SCI) are localized in the white matter, a recognized neural stem- and progenitor-cell (NSPC) niche of the adult spinal cord. Chemokines, as integrators of these processes, might also be important determinants of this NSPC niche. CCL3/CCR1, CCL2/CCR2, and SDF-1,/CXCR4 were analyzed in the ventrolateral white matter after force defined thoracic SCI: Immunoreactivity (IR) density levels were measured 2 d, 7 d, 14 d, and 42 d on cervical (C 5), thoracic (T 5), and lumbar (L 5) levels. On day post operation (DPO) 42, chemokine inductions were further evaluated by real-time RT-PCR and Western blot analyses. Cellular phenotypes were confirmed by double labeling with markers for major cell types and NSPCs (nestin, Musashi-1, NG2, 3CB2, BLBP). Mitotic profiles were investigated in parallel by BrdU labeling. After lesion, chemokines were induced in the ventrolateral white matter on IR-, mRNA-, and protein-level. IR was generally more pronounced after severe lesions, with soaring increases of CCL2/CCR2 and continuous elevations of CCL3/CCR1. SDF-1, and CXCR4 IR induction was focused on thoracic levels. Chemokines/-receptors were co-expressed with astroglial, oligodendroglial markers, nestin, 3CB2 and BLBP by cells morphologically resembling radial glia on DPO 7 to DPO 42, and NG2 or Musashi-1 on DPO 2 and 7. In the white matter BrdU positive cells were significantly elevated after lesion compared with sham controls on all investigated time points peaking in the early time course on thoracic level: Here, chemokines were co-expressed by subsets of BrdU-labeled cells. These findings suggest an important role of chemokines/-receptors in the subpial white matter NSPC niche after SCI. © 2010 Wiley-Liss, Inc. [source]

Hippocampal synaptic transmission and LTP in vivo are intact following bilateral vestibular deafferentation in the rat

HIPPOCAMPUS, Issue 4 2010
Yiwen Zheng
Abstract Numerous studies in animals and humans have shown that damage to the vestibular system in the inner ear results in spatial memory deficits, presumably because areas of the brain such as the hippocampus require vestibular input to accurately represent the spatial environment. Consistent with this hypothesis, studies in animals have demonstrated that complete bilateral vestibular deafferentation (BVD) causes a disruption of place cell firing as well as theta activity. The aim of this study was to investigate whether BVD in rats affects baseline field potentials (field excitatory postsynaptic potentials and population spikes) and long-term potentiation (LTP) in CA1 and the dentate gyrus (DG) of awake freely moving rats up to 43 days post-BVD and of anesthetized rats at 7 months post-BVD. Compared to sham controls, BVD had no significant effect on either baseline field potentials or LTP in either condition. These results suggest that although BVD interferes with the encoding, consolidation, and/or retrieval of spatial memories and the function of place cells, these changes are not related to detectable in vivo decrements in basal synaptic transmission or LTP, at least in the investigated pathways. © 2009 Wiley-Liss, Inc. [source]

Synaptic protein expression in the medial temporal lobe and frontal cortex following chronic bilateral vestibular loss

HIPPOCAMPUS, Issue 5 2008
Matthew Goddard
Abstract Several studies have reported that bilateral vestibular deafferentation (BVD) results in the disruption of place cell function and theta activity in the hippocampus. Recent magnetic resonance imaging (MRI) studies in humans demonstrated that bilateral but not unilateral vestibular loss is associated with a bilateral atrophy of the hippocampus. In this study we investigated whether BVD in rats resulted in changes in the expression of four proteins related to neuronal plasticity, synaptophysin, SNAP-25, drebrin and neurofilament-L, in the hippocampal subregions (CA1, CA2/3, the DG) and the entorhinal (EC), perirhinal (PRC) and frontal cortices (FC), using western blotting. At 6 months following BVD, there were no significant differences in the expression of synaptophysin in any region. There were also no significant differences in SNAP-25 expression in CA1, CA2/3, EC, PRC, or the FC; however, there was a significant increase in SNAP-25 expression in the DG compared to sham controls. Drebrin A and E expression was significantly reduced in the EC and drebrin A was significantly reduced in the FC of BVD animals. NF-L expression was not significantly different in CA1, CA2/3, DG, EC, or the PRC. However, its expression was significantly reduced in the FC of BVD animals. These data suggest that circumscribed neurochemical changes in SNAP-25, drebrin and NF-L expression occur in the DG, EC, and the FC over 6 months following BVD. © 2008 Wiley-Liss, Inc. [source]

RANKL Inhibition with Osteoprotegerin Increases Bone Strength by Improving Cortical and Trabecular bone Architecture in Ovariectomized Rats,,

Persistent Deficits in Heart Rate Response Habituation Following Neonatal Binge Ethanol Exposure

ALCOHOLISM, Issue 9 2009
Katherine C. Morasch
Background:, We have previously shown that the rate of habituation of the heart rate orienting response to a novel odor in rats is negatively affected by neonatal ethanol exposure. Thus far, however, only young rats (16 days of age) have been tested. Given the persistence of attention and memory problems evident in humans exposed to ethanol in utero, the purpose of this experiment was to examine the longer-term consequences of ethanol exposure on response habituation. Methods:, Ethanol (5.25 g/kg/d) was administered intragastrically to male and female Sprague-Dawley rats on postnatal days (PD) 4 to 9, and controls were given sham intubations. Animals were tested for heart rate orienting and response habituation to a novel olfactory stimulus (amyl acetate) on PD 16, 23, or 30. Results:, Animals tested on PD 16 or 23 showed normal heart rate deceleration to the novel odor, a measure of the orienting response. However, ethanol-treated subjects showed impaired response habituation compared with sham controls. While controls exhibited complete habituation within 4 to 5 trials, ethanol-treated animals continued to respond throughout the testing session, with little decrement in heart rate response magnitude across 10 stimulus presentations. A different pattern of responding was observed in animals tested during adolescence (PD 30). Control animals failed to show the typical heart rate decrease indicative of orienting, and instead showed a tendency toward tachycardia. In contrast, ethanol-treated animals tested on PD 30 showed orienting bradycardia that persisted for several trials. Conclusions:, These data suggest that there are relatively long-term consequences of neonatal ethanol exposure on nonassociative memory. This impairment in habituation may be relevant to the distractibility and poor focused attention that is pervasive among humans diagnosed with fetal alcohol spectrum disorders. [source]

Characterization of the Acute Cardiac Electrophysiologic Effects of Ethanol in Dogs

ALCOHOLISM, Issue 9 2007
Guilherme Fenelon
Background: Alcohol has been related to atrial fibrillation (holiday heart syndrome), but its electrophysiologic actions remain unclear. Methods: We evaluated the effects of alcohol in 23 anesthetized dogs at baseline and after 2 cumulative intravenous doses of ethanol: first dose 1.5 ml/kg (plasma level 200 mg/dl); second dose 1.0 ml/kg (279 mg/dl). In 13 closed-chest dogs (5 with intact autonomic nervous system, 5 under combined autonomic blockade and 3 sham controls), electrophysiologic evaluation and monophasic action potential (MAP) recordings were undertaken in the right atrium and ventricle. In 5 additional dogs, open-chest biatrial epicardial mapping with 8 bipoles on Bachmann's bundle was undertaken. In the remaining 5 dogs, 2D echocardiograms and ultrastructural analysis were performed. Results: In closed-chest dogs with intact autonomic nervous system, ethanol had no effects on surface electrocardiogram and intracardiac variables. At a cycle length of 300 milliseconds, no effects were noted on atrial and ventricular refractoriness and on the right atrial MAP. These results were not altered by autonomic blockade. No changes occurred in sham controls. In open-chest dogs, ethanol did not affect inter-atrial conduction time, conduction velocity, and wavelength. Atrial arrhythmias were not induced in any dog, either at baseline or after ethanol. Histological and ultrastructural findings were normal but left ventricular (LV) ejection fraction decreased in treated dogs (77 vs. 73 vs. 66%; p = 0.04). Conclusion: Ethanol at medium and high doses depresses LV systolic function but has no effects on atrial electrophysiological parameters. These findings suggest that acute alcoholic intoxication does not directly promote atrial arrhythmias. [source]

Methylprednisolone exacerbates axonal loss following optic nerve trauma in rats

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2002
KD Steinsapir
PURPOSE: This study investigates the clinical dogma that very high doses of methylprednisolone helpful in spinal cord injury are also helpful in optic nerve trauma. Methods: The right optic nerve of 29 male rats received a 5 second traumatic crush followed 30 minutes later by one of five intravenous treatments (methylprednisolone 30 mg/kg, 60 mg/kg, 90 mg/kg, 120 mg/kg, or saline). Treatment was continued for three additional administrations at 6 hour intervals. Untreated sham controls (n = 7) were also prepared. Six weeks after injury, animals were sacrificed, perfused and optic nerves systematically counted. RESULTS: Axon counts (means +/, s.e.m.) were as follows: Saline = 16,670 +/, 8,900 (n = 5); Methylprednisolone: 30 mg/kg = 8,098 +/, 4,741 (n = 5); 60 mg/kg = 6,925 +/, 6,517 (n = 4); 90 mg/kg = 2,663 +/, 2,653 (n = 4); 120 mg/kg = 6,149 +/, 3,487 (n = 6). Consequently, the data revealed that saline treated animals retained more axons than those that were administered methylprednisolone (p < 0.02). CONCLUSIONS: We conclude that methylprednisolone exacerbates axonal loss following crush injury in the rat optic nerve. Based on the results of this study, clinical studies of traumatic optic neuropathy in the future should also examine the possibility that corticosteroid treatment may have an adverse effect on visual outcome following optic nerve trauma. [source]

Nuclear factor-,B inhibition improves myocardial contractility in rats with cirrhotic cardiomyopathy

Vascular endothelial growth factor gene expression in middle cerebral artery occlusion in the rat

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2005
F. Lennmyr
Background:, Focal cerebral ischemia induces up-regulation of angiogenic growth factors such as vascular endothelial growth factor (VEGF), which may have both beneficial and harmful effects to the ischemic brain. Vascular endothelial growth factor is up-regulated in models of brain ischemia, but the underlying mechanisms in vivo remain unclear. In the present report we have investigated the concomitant changes in VEGF and glyceraldehyde dehydrogenase (GAPDH) mRNA expression in a model of permanent and transient cerebral ischemia. Methods:, Male Sprague-Dawley rats were exposed to permanent or transient (2 h) middle cerebral artery occlusion (PMCAO, TMCAO). Brain samples were collected at survival times ranging from 6 h to 1 week, and the levels of VEGF164 and GAPDH mRNA were determined using reverse-transcriptase real-time polymerase chain reaction (RT-PCR). Results:, The VEGF mRNA levels decreased gradually over the observation period in a similar manner in both PMCAO and TMCAO. Maximum levels, seen at early observation time points, did not significantly deviate from sham controls. No statistically significant changes in GAPDH mRNA levels were observed, but there was a tendency towards a postischemic decrease with subsequent return to control levels over time. The VEGF/GAPDH ratio followed a pattern of decrease similar to VEGF mRNA alone. Conclusion:, The VEGF mRNA levels at 6 h after MCAO remain near baseline and thereafter decline, regardless of whether the occlusion is permanent or transient (2 h). The findings raise the question of other than transcriptional regulation of VEGF in cerebral ischemia. [source]

Effects of 60 Hz 14 µT magnetic field on the apoptosis of testicular germ cell in mice

BIOELECTROMAGNETICS, Issue 1 2009
Yoon-Won Kim
Abstract We recently reported that continuous exposure, for 8 weeks, of extremely low frequency (ELF) magnetic field (MF) of 0.1 or 0.5 mT might induce testicular germ cell apoptosis in BALB/c mice. In that report, the ELF MF exposure did not significantly affect the body weight or testicular weight, but significantly increased the incidence of testicular germ cell death. In the present study, we aimed to further characterize the effect of a 16-week continuous exposure to ELF MF of 14 or 200 µT on testicular germ cell apoptosis in mice. There were no significant effects of MF on body weight and testosterone levels in mice. In TUNEL staining (In situ terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling), germ cells showed a significantly higher apoptotic rate in exposed mice than in sham controls (P,<,0.001). TUNEL-positive cells were mainly spermatogonia. In an electron microscopic study, degenerating spermatogonia showed condensation of nuclear chromatin similar to apoptosis. These results indicate that apoptosis may be induced in spermatogenic cells in mice by continuous exposure to 60 Hz MF of 14 µT. Bioelectromagnetics 30:66,72, 2009. © 2008 Wiley-Liss, Inc. [source]

Continuous wave and simulated GSM exposure at 1.8 W/kg and 1.8 GHz do not induce hsp16-1 heat-shock gene expression in Caenorhabditis elegans

BIOELECTROMAGNETICS, Issue 2 2008
Adam S. Dawe
Abstract Recent data suggest that there might be a subtle thermal explanation for the apparent induction by radiofrequency (RF) radiation of transgene expression from a small heat-shock protein (hsp16-1) promoter in the nematode, Caenorhabditis elegans. The RF fields used in the C. elegans study were much weaker (SAR 5,40 mW,kg,1) than those routinely tested in many other published studies (SAR ,2 W,kg,1). To resolve this disparity, we have exposed the same transgenic hsp16-1::lacZ strain of C. elegans (PC72) to higher intensity RF fields (1.8 GHz; SAR ,1.8 W,kg,1). For both continuous wave (CW) and Talk-pulsed RF exposures (2.5 h at 25 °C), there was no indication that RF exposure could induce reporter expression above sham control levels. Thus, at much higher induced RF field strength (close to the maximum permitted exposure from a mobile telephone handset), this particular nematode heat-shock gene is not up-regulated. However, under conditions where background reporter expression was moderately elevated in the sham controls (perhaps as a result of some unknown co-stressor), we found some evidence that reporter expression may be reduced by ,15% following exposure to either Talk-pulsed or CW RF fields. Bioelectromagnetics 29:92,99, 2008. © 2007 Wiley-Liss, Inc. [source]

A small temperature rise may contribute towards the apparent induction by microwaves of heat-shock gene expression in the nematode Caenorhabditis Elegans

BIOELECTROMAGNETICS, Issue 2 2006
Adam S. Dawe
Abstract We have previously reported that low intensity microwave exposure (0.75,1.0 GHz CW at 0.5 W; SAR 4,40 mW/kg) can induce an apparently non-thermal heat-shock response in Caenorhabditis elegans worms carrying hsp16-1::reporter genes. Using matched copper TEM cells for both sham and exposed groups, we can detect only modest reporter induction in the latter exposed group (15,20% after 2.5 h at 26 °C, rising to ,50% after 20 h). Traceable calibration of our copper TEM cell by the National Physical Laboratory (NPL) reveals significant power loss within the cell (8.5% at 1.0 GHz), accompanied by slight heating of exposed samples (,0.3 °C at 1.0 W). Thus, exposed samples are in fact slightly warmer (by ,0.2 °C at 0.5 W) than sham controls. Following NPL recommendations, our TEM cell design was modified with the aim of reducing both power loss and consequent heating. In the modified silver-plated cell, power loss is only 1.5% at 1.0 GHz, and sample warming is reduced to ,0.15 °C at 1.0 W (i.e., ,0.1 °C at 0.5 W). Under sham:sham conditions, there is no difference in reporter expression between the modified silver-plated TEM cell and an unmodified copper cell. However, worms exposed to microwaves (1.0 GHz and 0.5 W) in the silver-plated cell also show no detectable induction of reporter expression relative to sham controls in the copper cell. Thus, the 20% "microwave induction" observed using two copper cells may be caused by a small temperature difference between sham and exposed conditions. In worms incubated for 2.5 h at 26.0, 26.2, and 27.0 °C with no microwave field, there is a consistent and significant increase in reporter expression between 26.0 and 26.2 °C (by ,20% in each of the six independent runs), but paradoxically expression levels at 27.0 °C are similar to those seen at 26.0 °C. This surprising result is in line with other evidence pointing towards complex regulation of hsp16-1 gene expression across the sub-heat-shock range of 25,27.5 °C in C. elegans. We conclude that our original interpretation of a non-thermal effect of microwaves cannot be sustained; at least part of the explanation appears to be thermal. Bioelectromagnetics 27:88,97, 2006. © 2005 Wiley-Liss, Inc. [source]

Tumour growth following portal branch ligation in an experimental model of liver metastases,

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 6 2010
O. Kollmar
Background: Portal branch ligation (PBL) is being used increasingly before hepatectomy for colorectal metastases. This study evaluated the effect of PBL on angiogenesis, growth factor expression and tumour growth in a mouse model of hepatic colorectal metastases. Methods: CT26.WT cells were implanted into the left liver lobe of BALB/c mice. Animals underwent PBL of the left liver lobe or sham treatment. Angiogenesis, microcirculation, growth factor expression, cell proliferation and tumour growth were studied over 14 and 21 days by intravital multifluorescence microscopy, laser Doppler flowmetry, immunohistochemistry and western blotting. Results: Left hilar blood flow and tumour microcirculation were significantly diminished during the first 7 days after PBL. This resulted in tumour volume being 20 per cent less than in sham controls by day 14. Subsequently, PBL-treated animals demonstrated recovery of left hilar blood flow and increased expression of hepatocyte growth factor and transforming growth factor ,, associated with increased cell proliferation and acceleration of growth by day 21. Conclusion: PBL initially reduced vascular perfusion and tumour growth, but this was followed by increased growth factor expression and cell proliferation. This resulted in delayed acceleration of tumour growth, which might explain the stimulated tumour growth observed occasionally after PBL. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

Role of mast cells in the development of pancreatitis-induced multiple organ dysfunction

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 2 2002
M. Dib
Background: Activated mast cells can produce and release a number of inflammatory mediators involved in the pathophysiology of acute conditions. The aim of the present study was to evaluate the role of activated tissue mast cells in the pathogenesis of multiple organ dysfunction syndrome following acute pancreatitis (AP). Methods: AP was induced by the intraductal infusion of 5 per cent sodium taurodeoxycholate in the rat. Some 30 min before induction of AP, a mast cell stabilizer (sodium cromoglycate (SCG)) or antihistamines (pyrilamine, cyproheptadine, meclizine and amitriptyline) were administered intra peritoneally. Plasma exudation of radiolabelled albumin, histamine, myeloperoxidase (MPO), monocyte chemoattractant protein (MCP) 1 and adhesion molecules (platelet endothelial cell adhesion molecule (PECAM) 1 and L-selectin) were measured. Results: The mast cell stabilizer significantly reduced plasma exudation in the pancreas, colon and lungs (P < 0·05), decreased the release of histamine at 1 h (P < 0·05), and reduced MPO activity and MCP-1 levels in the colon and lungs (P < 0·05) but not in the pancreas. Expression of PECAM-1 and L-selectin on total circulating leucocytes in rats with AP and SCG pretreatment did not differ from that in sham controls, while levels in animals that had AP and saline pretreatment were half of those seen following sham operation. Conclusion: Activation of mast cells after induction of AP is involved in the development of endothelial barrier dysfunction in both the pancreas and extrapancreatic organs/tissues, particularly in the lungs and colon. This may, at least partly, contribute to the sequential development of multiple organ dysfunction and organ/tissue-specific endothelial barrier dysfunction. © 2002 British Journal of Surgery Society Ltd [source]