Anesthetic activity of plant essential oils on Cyprinus carpio (koi carp).

PubMed

Khumpirapang, Nattakanwadee; Pikulkaew, Surachai; Anuchapreeda, Songyot; Okonogi, Siriporn

2018-03-19

The aims of this study were to investigate the anesthetic and cytotoxic effects of essential oils (EOs) of Ocimum basilicum (OBO), O. canum (OCO), and O. sanctum (OSO) on Cyprinus carpio (koi carp). For anesthetic effect, induction time to surgical anesthesia and recovery time were determined. For cytotoxicity effect, viability of fish peripheral blood nuclear cells (PBMCs) was investigated. Results indicated that increasing oil concentration caused significant (p < 0.01) decrease of induction time. OSO at 100, 200, and 300 mg/L gave the induction time of 169.5 ± 10.2, 62.8 ± 2.3, 45.3 ± 2.2 sec, respectively, significantly shorter than OCO, and OBO. The recovery time of anesthetized fish was dose dependent (p <0.01). Among them, OCO showed the longest recovery time of 313.0 ± 8.1, 420.7 ± 12.6, 616.6 ± 12.1 sec for concentrations of 100, 200, and 300 mg/L, respectively, followed by OSO and OBO, respectively. Within 10 min contact time of the EOs and fish PBMCs, the fish PBMC viability was higher than 80%. Increase contact time and EO concentration caused an increase in cytotoxicity to fish PBMC. OBO showed less toxic than OSO and OCO. Based on the desired induction and recovery times for anesthetizing koi carp, OBO, OCO, and OSO at 300, 200, and 100 mg/L, respectively were suggested to be the most suitable. It was concluded that OBO, OCO, and OSO can be used as natural anesthetics for fish.

GABAergic Transmission in Rat Pontine Reticular Formation Regulates the Induction Phase of Anesthesia and Modulates Hyperalgesia Caused by Sleep Deprivation

PubMed Central

Vanini, Giancarlo; Nemanis, Kriste; Baghdoyan, Helen A.; Lydic, Ralph

2014-01-01

The oral part of the pontine reticular formation (PnO) contributes to the regulation of sleep, anesthesia, and pain. The role of PnO GABA in modulating these states remains incompletely understood. The present study used time to Loss and time to Resumption of Righting Response (LoRR and RoRR) as surrogate measures of loss and resumption of consciousness. This study tested three hypotheses: (1) pharmacologically manipulating GABA levels in rat PnO alters LoRR, RoRR, and nociception; (2) propofol decreases GABA levels in the PnO; and (3) inhibiting GABA synthesis in the PnO blocks hyperalgesia caused by sleep deprivation. Administering a GABA synthesis inhibitor (3-MPA) or a GABA uptake inhibitor (NPA) into rat PnO significantly altered LoRR caused by propofol. 3-MPA significantly decreased LoRR for propofol (−18%). NPA significantly increased LoRR during administration of propofol (36%). Neither 3-MPA nor NPA altered RoRR following cessation of propofol or isoflurane delivery. The finding that LoRR was decreased by 3-MPA and increased by NPA is consistent with measures showing that extracellular GABA levels in the PnO were decreased (41%) by propofol. Thermal nociception was significantly decreased by 3-MPA and increased by NPA, and 3-MPA blocked the hyperalgesia caused by sleep deprivation. The results demonstrate that GABA levels in the PnO regulate the time for loss of consciousness caused by propofol, extend the concept that anesthetic induction and emergence are not inverse processes, and suggest that GABAergic transmission in the PnO mediates hyperalgesia caused by sleep loss. PMID:24674578

GABAergic transmission in rat pontine reticular formation regulates the induction phase of anesthesia and modulates hyperalgesia caused by sleep deprivation.

PubMed

Vanini, Giancarlo; Nemanis, Kriste; Baghdoyan, Helen A; Lydic, Ralph

2014-07-01

The oral part of the pontine reticular formation (PnO) contributes to the regulation of sleep, anesthesia and pain. The role of PnO γ-aminobutyric acid (GABA) in modulating these states remains incompletely understood. The present study used time to loss and time to resumption of righting response (LoRR and RoRR) as surrogate measures of loss and resumption of consciousness. This study tested three hypotheses: (i) pharmacologically manipulating GABA levels in rat PnO alters LoRR, RoRR and nociception; (ii) propofol decreases GABA levels in the PnO; and (iii) inhibiting GABA synthesis in the PnO blocks hyperalgesia caused by sleep deprivation. Administering a GABA synthesis inhibitor [3-mercaptopropionic acid (3-MPA)] or a GABA uptake inhibitor [nipecotic acid (NPA)] into rat PnO significantly altered LoRR caused by propofol. 3-MPA significantly decreased LoRR for propofol (-18%). NPA significantly increased LoRR during administration of propofol (36%). Neither 3-MPA nor NPA altered RoRR following cessation of propofol or isoflurane delivery. The finding that LoRR was decreased by 3-MPA and increased by NPA is consistent with measures showing that extracellular GABA levels in the PnO were decreased (41%) by propofol. Thermal nociception was significantly decreased by 3-MPA and increased by NPA, and 3-MPA blocked the hyperalgesia caused by sleep deprivation. The results demonstrate that GABA levels in the PnO regulate the time for loss of consciousness caused by propofol, extend the concept that anesthetic induction and emergence are not inverse processes, and suggest that GABAergic transmission in the PnO mediates hyperalgesia caused by sleep loss. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Anesthetic induction with guaifenesin and propofol in adult horses.

PubMed

Brosnan, Robert J; Steffey, Eugene P; Escobar, André; Palazoglu, Mine; Fiehn, Oliver

2011-12-01

To evaluate whether guaifenesin can prevent adverse anesthetic induction events caused by propofol and whether a guaifenesin-propofol induction combination has brief cardiovascular effects commensurate with rapid drug washout. 8 healthy adult horses. Guaifenesin was administered IV for 3 minutes followed by IV injection of a bolus of propofol (2 mg/kg). Additional propofol was administered if purposeful movement was detected. Anesthesia was maintained for 2 hours with isoflurane or sevoflurane at 1.2 times the minimum alveolar concentration with controlled normocapnic ventilation. Normotension was maintained via a dobutamine infusion. Plasma concentrations of propofol and guaifenesin were measured every 30 minutes. Mean ± SD guaifenesin and propofol doses inducing anesthesia in half of the horses were 73 ± 18 mg/kg and 2.2 ± 0.3 mg/kg, respectively. No adverse anesthetic induction events were observed. By 70 minutes, there was no significant temporal change in the dobutamine infusion rate required to maintain normotension for horses anesthetized with isoflurane or sevoflurane. Mean plasma guaifenesin concentrations were 122 ± 30 μM, 101 ± 33 μM, 93 ± 28 μM, and 80 ± 24 μM at 30, 60, 90, and 120 minutes after anesthetic induction, respectively. All plasma propofol concentrations were below the limit of quantitation. Guaifenesin prevented adverse anesthetic induction events caused by propofol. Guaifenesin (90 mg/kg) followed by propofol (3 mg/kg) should be sufficient to immobilize > 99% of calm healthy adult horses. Anesthetic drug washout was rapid, and there was no change in inotrope requirements after anesthesia for 70 minutes.

Dexamethasone hepatic induction in rats subsequently treated with high dose buprenorphine does not lead to respiratory depression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hreiche, Raymond; Megarbane, Bruno; Pirnay, Stephane

In humans, asphyxic deaths and severe poisonings have been attributed to high-dosage buprenorphine, a maintenance therapy for heroin addiction. However, in rats, intravenous buprenorphine at doses up to 90 mg kg{sup -1} was not associated with significant effects on arterial blood gases. In contrast, norbuprenorphine, the buprenorphine major cytochrome P450 (CYP) 3A-derived metabolite, is a potent respiratory depressant. Thus, our aim was to study the consequences of CYP3A induction on buprenorphine-associated effects on resting ventilation in rats. We investigated the effects on ventilation of 30 mg kg{sup -1} buprenorphine alone or following cytochrome P450 (CYP) 3A induction with dexamethasone, usingmore » whole body plethysmography (N = 24) and arterial blood gases (N = 12). Randomized animals in 4 groups received sequential intraperitoneal dosing with: (dexamethasone [days 1-3] + buprenorphine [day 4]), (dexamethasone solvent [days 1-3] + buprenorphine [day 4]), (dexamethasone [days 1-3] + buprenorphine solvent [day 4]), or (dexamethasone solvent [days 1-3] + buprenorphine solvent [day 4]). Buprenorphine alone caused a significant rapid and sustained increase in the inspiratory time (P < 0.001), without significant effects on the respiratory frequency, the tidal volume, the minute volume, or arterial blood gases. In dexamethasone-pretreated rats, there was no significant alteration in the respiratory parameters, despite CYP3A induction and significant increase of the ratio of plasma norbuprenorphine-to-buprenorphine concentrations. In conclusion, dexamethasone did not modify the effects of 30 mg kg{sup -1} buprenorphine on rat ventilation. Our results suggest a limited role of drug-mediated CYP3A induction in the occurrence of buprenorphine-attributed respiratory depression in addicts.« less

Delayed Induction of Human NTE (PNPLA6) Rescues Neurodegeneration and Mobility Defects of Drosophila swiss cheese (sws) Mutants.

PubMed

Sujkowski, Alyson; Rainier, Shirley; Fink, John K; Wessells, Robert J

2015-01-01

Human PNPLA6 gene encodes Neuropathy Target Esterase protein (NTE). PNPLA6 gene mutations cause hereditary spastic paraplegia (SPG39 HSP), Gordon-Holmes syndrome, Boucher-Neuhäuser syndromes, Laurence-Moon syndrome, and Oliver-McFarlane syndrome. Mutations in the Drosophila NTE homolog swiss cheese (sws) cause early-onset, progressive behavioral defects and neurodegeneration characterized by vacuole formation. We investigated sws5 flies and show for the first time that this allele causes progressive vacuolar formation in the brain and progressive deterioration of negative geotaxis speed and endurance. We demonstrate that inducible, neuron-specific expression of full-length human wildtype NTE reduces vacuole formation and substantially rescues mobility. Indeed, neuron-specific expression of wildtype human NTE is capable of rescuing mobility defects after 10 days of adult life at 29°C, when significant degeneration has already occurred, and significantly extends longevity of mutants at 25°C. These results raise the exciting possibility that late induction of NTE function may reduce or ameliorate neurodegeneration in humans even after symptoms begin. In addition, these results highlight the utility of negative geotaxis endurance as a new assay for longitudinal tracking of degenerative phenotypes in Drosophila.

Induction of heme oxygenase-1 by chamomile protects murine macrophages against oxidative stress

PubMed Central

Bhaskaran, Natarajan; Shukla, Sanjeev; Kanwal, Rajnee; Srivastava, Janmejai K; Gupta, Sanjay

2012-01-01

Aims Protection of cells from oxidative insult may be possible through direct scavenging of reactive oxygen species, or through stimulation of intracellular antioxidant defense mechanisms by induction of antioxidant gene expression. In this study we investigated the cytoprotective effect of chamomile and elucidated the underlying mechanisms. Main Methods The cytoprotective effect of chamomile was examined on H2O2-induced cellular stress in RAW 264.7 murine macrophages. Key Findings RAW 264.7 murine macrophages treated with chamomile were protected from cell death caused by H2O2. Treatment with 50 μM H2O2 for 6 h caused significant increase in cellular stress accompanied by cell death in RAW 264.7 macrophages. Pretreatment with chamomile at 10-20 μg/mL for 16 h followed by H2O2 treatment protected the macrophages against cell death. Chamomile exposure significantly increased the expression of antioxidant enzymes viz. heme oxygenase-1 (HO-1), peroxiredoxin-1 (Prx-1), and thioredoxin-1 (Trx-1) in a dose-dependent manner, compared with their respective controls. Chamomile increased nuclear translocation of Nrf2 with increased phosphorylated Nrf2 levels, and binding to the antioxidant response element in the nucleus. Significance These molecular findings for the first time provide insights into the mechanisms underlying the induction of phase 2 enzymes through the Keap1-Nrf2 signaling pathway by chamomile, and provide evidence that chamomile possesses antioxidant and cytoprotective properties. PMID:22683429

Decreased term and postterm birthweight in the United States: impact of labor induction.

PubMed

Zhang, Xun; Joseph, K S; Kramer, Michael S

2010-08-01

We sought to assess recent trends in falling mean birthweight (BW) and gestational age (GA) among US non-Hispanic white singleton live births >or=37 weeks of gestation and the contribution of increased rates of induction to these trends. This was an ecological study based on US vital statistics from 1992 through 2003. From 1992 through 2003, mean BW fell by 37 g, mean GA by 3 days, and macrosomia rates by 25%. Rates of induction nearly doubled from 14% to 27%. Our ecological state-level analysis showed that the increased rate of induction was significantly associated with reduced mean BW (r = -0.54; 95% confidence interval [CI], -0.71 to -0.29), mean GA (r = -0.44; 95% CI, -0.65 to -0.17), and rate of macrosomia (r = -0.55; 95% CI, -0.74 to -0.32). Increasing use of induction is a likely cause of the observed recent declines in BW and GA. The impact of these trends on infant and long-term health warrants attention and investigation. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Interactive Effects of Jasmonic Acid, Salicylic Acid, and Gibberellin on Induction of Trichomes in Arabidopsis1

PubMed Central

Traw, M. Brian; Bergelson, Joy

2003-01-01

Leaf trichomes protect plants from attack by insect herbivores and are often induced following damage. Hormonal regulation of this plant induction response has not been previously studied. In a series of experiments, we addressed the effects of artificial damage, jasmonic acid, salicylic acid, and gibberellin on induction of trichomes in Arabidopsis. Artificial damage and jasmonic acid caused significant increases in trichome production of leaves. The jar1-1 mutant exhibited normal trichome induction following treatment with jasmonic acid, suggesting that adenylation of jasmonic acid is not necessary. Salicylic acid had a negative effect on trichome production and consistently reduced the effect of jasmonic acid, suggesting negative cross-talk between the jasmonate and salicylate-dependent defense pathways. Interestingly, the effect of salicylic acid persisted in the nim1-1 mutant, suggesting that the Npr1/Nim1 gene is not downstream of salicylic acid in the negative regulation of trichome production. Last, we found that gibberellin and jasmonic acid had a synergistic effect on the induction of trichomes, suggesting important interactions between these two compounds. PMID:14551332

Impact of Glycerol as Carbon Source onto Specific Sugar and Inducer Uptake Rates and Inclusion Body Productivity in E. coli BL21(DE3).

PubMed

Kopp, Julian; Slouka, Christoph; Ulonska, Sophia; Kager, Julian; Fricke, Jens; Spadiut, Oliver; Herwig, Christoph

2017-12-21

The Gram-negative bacterium E. coli is the host of choice for a multitude of used recombinant proteins. Generally, cultivation is easy, media are cheap, and a high product titer can be obtained. However, harsh induction procedures using isopropyl β-d-1 thiogalactopyranoside as inducer are often referred to cause stress reactions, leading to a phenomenon known as "metabolic" or "product burden". These high expressions of recombinant proteins mainly result in decreased growth rates and cell lysis at elevated induction times. Therefore, approaches tend to use "soft" or "tunable" induction with lactose and reduce the stress level of the production host. The usage of glucose as energy source in combination with lactose as induction reagent causes catabolite repression effects on lactose uptake kinetics and as a consequence reduced product titer. Glycerol-as an alternative carbon source-is already known to have positive impact on product formation when coupled with glucose and lactose in auto-induction systems, and has been referred to show no signs of repression when cultivated with lactose concomitantly. In recent research activities, the impact of different products on the lactose uptake using glucose as carbon source was highlighted, and a mechanistic model for glucose-lactose induction systems showed correlations between specific substrate uptake rate for glucose or glycerol (q s,C ) and the maximum specific lactose uptake rate (q s,lac,max ). In this study, we investigated the mechanistic of glycerol uptake when using the inducer lactose. We were able to show that a product-producing strain has significantly higher inducer uptake rates when being compared to a non-producer strain. Additionally, it was shown that glycerol has beneficial effects on viability of cells and on productivity of the recombinant protein compared to glucose.

Metabolic abnormalities associated with weight loss during chemoirradiation of head-and-neck cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Alexander; Jabbari, Siavash; Worden, Francis P.

2005-12-01

Purpose: Weight loss caused by acute mucositis and dysphagia is common during concurrent chemoirradiation (chemo-RT) of head-and-neck (HN) cancer. The metabolic consequences of weight loss during chemo-RT were investigated. Patients and Methods: Ninety-six patients with locally advanced HN cancer were treated from 1995 to 2001 on protocols that consisted of 1 to 2 cycles of induction cisplatin/5-fluorouracil followed by irradiation (70 Gy over 7 weeks) concurrent with cisplatin (100 mg/m{sup 2} every 3 weeks). Body weights and metabolic evaluations were obtained before and during induction chemotherapy and chemo-RT. Greatest percent changes in weight and in the laboratory values were calculatedmore » for each phase of therapy. Results: During induction chemotherapy, significant changes were found in BUN, BUN:creatinine ratio, HCO{sub 3}, Mg, and albumin, but not in creatinine, Na, K, or weight. During chemo-RT, significant additional changes were observed in all parameters measured, including increases in BUN, creatinine, BUN: creatinine ratio, and HCO{sub 3} and decreases in Mg, albumin, Na, K, and weight. The magnitude of most of these changes was significantly greater during chemo-RT than during induction chemotherapy. During chemo-RT, 35% of the patients had more than 10% body weight loss and 6 patients had an increase in creatinine of more than 100%, including 5 patients with Grade 2 nephrotoxicity, all of whom had weight loss 10% or more. Significant correlations were found between weight loss and creatinine (p < 0.0001) or BUN (p = 0.0002) rises, but not with BUN:creatinine ratio or other metabolic changes. Age, gender, tobacco history, hypertension, and diabetes mellitus were not significant predictors of nephrotoxicity. Conclusions: Weight loss during cisplatin-containing chemo-RT was found to be associated with reduced kidney function. These findings do not establish cause-effect relationships; however, they highlight the importance of intensive supportive measures of nutrition and hydration beyond standard hydration during cisplatin administration. These intensive measures should be enacted before a 10% weight loss is reached.« less

Methamphetamine induces heme oxygenase-1 expression in cortical neurons and glia to prevent its toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Y.-N.; Wu, C.-H.; Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan 114

2009-11-01

The impairment of cognitive and motor functions in humans and animals caused by methamphetamine (METH) administration underscores the importance of METH toxicity in cortical neurons. The heme oxygenase-1 (HO-1) exerts a cytoprotective effect against various neuronal injures; however, it remains unclear whether HO-1 is involved in METH-induced toxicity. We used primary cortical neuron/glia cocultures to explore the role of HO-1 in METH-induced toxicity. Exposure of cultured cells to various concentrations of METH (0.1, 0.5, 1, 3, 5, and 10 mM) led to cytotoxicity in a concentration-dependent manner. A METH concentration of 5 mM, which caused 50% of neuronal death andmore » glial activation, was chosen for subsequent experiments. RT-PCR and Western blot analysis revealed that METH significantly induced HO-1 mRNA and protein expression, both preceded cell death. Double and triple immunofluorescence staining further identified HO-1-positive cells as activated astrocytes, microglia, and viable neurons, but not dying neurons. Inhibition of the p38 mitogen-activated protein kinase pathway significantly blocked HO-1 induction by METH and aggravated METH neurotoxicity. Inhibition of HO activity using tin protoporphyrine IX significantly reduced HO activity and exacerbated METH neurotoxicity. However, prior induction of HO-1 using cobalt protoporphyrine IX partially protected neurons from METH toxicity. Taken together, our results suggest that induction of HO-1 by METH via the p38 signaling pathway may be protective, albeit insufficient to completely protect cortical neurons from METH toxicity.« less

Study of the pelvic floor muscles in vaginismus: a concept of pathogenesis.

PubMed

Shafik, Ahmed; El-Sibai, Olfat

2002-10-10

Neither the cause of vaginismus nor the muscles involved are precisely identified. To define the involved muscles and their role in the pathogenesis of vaginismus. The EMG activity of the levator ani (LA), puborectalis (PR) and bulbocavernosus (BC) muscles was studied in seven female patients (age (years): 25.6(mean)+/-1.2(S.D.)) and seven healthy volunteers who matched the patients in age. Recordings were performed at rest and during induction of vaginismus by a vaginal dilator. Upon approximating the vaginal dilator to the vaginal introitus or introducing it into the vagina of the healthy volunteers, the EMG activity of the LA, PR and BC muscles showed no significant difference from the basal activity. In the patients, the basal EMG activity of the examined muscles was significantly higher than that of the healthy volunteers (P<0.05). Upon vaginismus induction, the muscles showed a significant increase of the EMG activity (P<0.01). The latency recorded a mean of 14.2+/-2.3, 13.9+/-2.3 and 14.1+/-2.2ms (P>0.05) in the LA, PR and BC muscles, respectively. The muscle response was momentary lasting a mean of 31.2+/-5.7s. It was reproducible provided an off-time of a mean of 13.2+/-2.3s was observed. The pelvic floor muscles of vaginismus patients exhibited increased EMG activity at rest and on vaginismus induction; the cause is unknown. The concept of a disordered sacral reflex arc is put forward but needs further studies to be verified.

Canine parvovirus NS1 protein exhibits anti-tumor activity in a mouse mammary tumor model.

PubMed

Gupta, Shishir Kumar; Yadav, Pavan Kumar; Gandham, Ravi Kumar; Sahoo, A P; Harish, D R; Singh, Arvind Kumar; Tiwari, A K

2016-02-02

Many viral proteins have the ability to kill tumor cells specifically without harming the normal cells. These proteins, on ectopic expression, cause lysis or induction of apoptosis in the target tumor cells. Parvovirus NS1 is one of such proteins, which is known to kill high proliferating tumor cells. In the present study, we assessed the apoptosis inducing ability of canine parvovirus type 2 NS1 protein (CPV2.NS1) in vitro in 4T1 cells, and found it to cause significant cell death due to induction of apoptosis through intrinsic or mitochondrial pathway. Further, we also evaluated the oncolytic activity of CPV2.NS1 protein in a mouse mammary tumor model. The results suggested that CPV2.NS1 was able to inhibit the growth of 4T1 induced mouse mammary tumor as indicated by significantly reduced tumor volume, mitotic, AgNOR and PCNA indices. Further, inhibition of tumor growth was found to be because of induction of apoptosis in the tumor cells, which was evident by a significant increase in the number of TUNEL positive cells. Further, CPV2.NS1 was also able to stimulate the immune cells against the tumor antigens as indicated by the increased CD4+ and CD8+ counts in the blood of CVP2.NS1 treated mice. Further optimization of the delivery of NS1 protein and use of an adjuvant may further enhance its anti-tumor activity. Copyright © 2015 Elsevier B.V. All rights reserved.

Importance of positron emission tomography for assessing the response of primary and metastatic lesions to induction treatments in T4 esophageal cancer.

PubMed

Makino, Tomoki; Yamasaki, Makoto; Tanaka, Koji; Tatsumi, Mitsuaki; Takiguchi, Shuji; Hatazawa, Jun; Mori, Masaki; Doki, Yuichiro

2017-10-01

There is no consensus strategy for treatment of T4 esophageal cancer, and because of this, a better evaluation of treatment response is crucial to establish personalized therapies. This study aimed to establish a useful system for evaluating treatment response in T4 esophageal cancer. This study included 130 patients with cT4 esophageal cancer without distant metastasis who underwent 18 F-fluorodeoxyglucose-positron emission tomography before and after a series of induction treatments comprising chemoradiation or chemotherapy. We evaluated the maximal standardized uptake value and treatment response. The mean ± standard deviation of standardized uptake value in the primary tumor before and after induction treatments were 13.8 ± 4.4 and 5.4 ± 4.1, respectively, and the mean standardized uptake value decrease was 58.4%. The most significant difference in survival between positron emission tomography-primary tumor responders and nonresponders was at a decrease of 60% standardized uptake value, based on every 10% stepwise cutoff analysis (2-year cause-specific survival: 60.2 vs 23.5%; hazard ratio = 2.705; P < .0001). With this cutoff value, the resectability (P = .0307), pathologic response (P = .0004), and pT stage (P < .0001) were associated with positron emission tomography-primary tumor response. Univariate analysis of 2-year cause-specific survival indicated a correlation between cause-specific survival and clinical stages according to TNM classification, esophageal perforation, positron emission tomography-primary tumor response, lymph node status evaluated by positron emission tomography before and after induction treatments, and operative resection. Multivariate analysis further identified positron emission tomography-primary tumor response (hazard ratio = 2.354; P = .0107), lymph node status evaluated by positron emission tomography after induction treatments (hazard ratio = 1.966; P = .0089), and operative resection (hazard ratio = 2.012; P = .0245) as independent prognostic predictors. Positron emission tomography evaluation of the response of primary and metastatic lesions to induction treatments is important to formulate treatment strategies for cT4 esophageal cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Grapevine phenolics in xylem sap and tissues are significantly altered during infection by Xylella fastidiosa

USDA-ARS?s Scientific Manuscript database

Pierce’s disease of grapevine (PD), caused by the bacterial pathogen Xylella fastidiosa (X.f.), remains a serious problem for grape production in California and elsewhere. This research examined induction of phenolic compounds in grapevines (cv. Thompson Seedless) infected with X.f. over a six month...

Inductively coupled plasma mass spectrometer with laser ablation metal ions release detection in the human mouth

NASA Astrophysics Data System (ADS)

Kueerova, Hana; Dostalova, Tatjana; Prochazkova, J.

2002-06-01

Presence of more dental alloys in oral cavity often causes pathological symptoms. Due to various and multi-faced symptomatology, they tend to be a source of significant problems not only for the patient but also for the dentist. Metal ions released from alloys can cause subjective and objective symptoms in mouth. The aim of this study was detection of metal elements presence in saliva. There were 4 groups of examined persons: with intact teeth (15 individuals) with metallic restorations, pathological currents 5-30 (mu) A, multi-faced subjective symptomatology and uncharacteristic objective diagnosis (32 patients), with metallic restorations and no subjective symptoms (14 persons) and with metallic restorations, without pathological currents and with problems related to galvanism (13 patients). Presence of 14 metal elements was checked by inductively coupled plasma mass spectrometer with laser ablation. Nd:YAG laser detector was used. There were significant differences in content of silver, gold and mercury between persons with intact teeth and other three groups. There were no differences found between subjects with and without galvanic currents, and presence of subjective and objective symptoms.

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

PubMed Central

Öztürk, T.; Ağdanlı, D.; Bayturan, Ö.; Çıkrıkcı, C.; Keleş, G.T.

2015-01-01

Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc) prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25) or high-dose (1.2 mg/kg, group H, n=25) rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0), after induction (T1), after rocuronium (just before laryngoscopy; T2), 2 min after intubation (T3), and 5 min after intubation (T4). The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001), and 459 vs 434 ms in group H (P=0.005)]. The incidence of dysrhythmias in group C (28%) and in group H (24%) was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation. PMID:25714880

Kinetics of micronucleus induction and cytotoxicity caused by distinct antineoplastics and alkylating agents in vivo.

PubMed

Morales-Ramírez, Pedro; Vallarino-Kelly, Teresita; Cruz-Vallejo, Virginia

2014-01-30

This mini-review aims to compare the differences in the kinetics of the induction of micronucleated polychromatic erythrocytes (MN-PCE) and cytotoxicity by distinct antineoplastic and genotoxic agents in murine peripheral blood in vivo and to correlate these kinetics with the underlying processes. Comparisons were carried out using our previously obtained data with nominal doses causing similar levels of cytotoxicity, as measured in terms reduction of PCE. The aneuploidogens caused the most rapid induction of MN-PCEs and had the highest rates of cytotoxicity and genotoxicity. The promutagens cyclophosphamide and dimethylnitrosamine showed the most delayed responses and had the lowest genotoxic and cytotoxic efficiencies. DNA crosslinking agents had a similar delay of 4-5 h, greater than those of aneuploidogens, but differed in their cytotoxic and genotoxic efficiencies. Methylnitrosourea and 5-aza-cytidine caused greater delays than crosslinking agents. These delays can be due to the methylnitrosourea-mediated induction of formation of mono alkyl adducts which are interpreted as mismatches during DNA duplication, whereas 5-aza-cytidine requires incorporation into the DNA to induce breakage. This review allows us to conclude that the requirement for metabolic activation and the mechanisms of DNA breakage and of micronucleus induction are the main factors that affect the time of maximal MN-PCE induction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Evaluation of cytotoxic, genotoxic and inflammatory responses of micro- and nano-particles of granite on human lung fibroblast cell IMR-90.

PubMed

Ahmad, Iqbal; Khan, Mohd Imran; Patil, Govil; Chauhan, L K S

2012-02-05

Occupational exposure of granite workers is well known to cause lung impairment and silicosis. Toxicological profiles of different size particles of granite dust, however, are not yet understood. Present evaluation of micro- and nano-particles of granite dust as on human lung fibroblast cells IMR-90, revealed that their toxic effects were dose-dependent, and nanoparticles in general were more toxic. In this study we first demonstrated that nanoparticles caused oxidative stress, inflammatory response and genotoxicity, as seen by nearly 2 fold induction of ROS and LPO, mRNA levels of TNF-α and IL-1β, and induction in micronuclei formation. All these were significantly higher when compared with the effect of micro particles. Thus, the study suggests that separate health safety standards would be required for granite particles of different sizes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The Establishment of Metabolic Syndrome Model by Induction of Fructose Drinking Water in Male Wistar Rats

PubMed Central

Thent, Zar Chi; Sapri, Shaiful Ridzwan; Sahruddin, Natasya Nadia; Mohd Yusof, Mohd Rafizul; Haji Suhaimi, Farihah

2014-01-01

Background. Metabolic syndrome can be caused by modification of diet by means of consumption of high carbohydrate and high fat diet such as fructose. Aims. To develop a metabolic syndrome rat model by induction of fructose drinking water (FDW) in male Wistar rats. Methods. Eighteen male Wistar rats were fed with FDW 20% and FDW 25% for a duration of eight weeks. The physiological changes with regard to food and fluid intake, as well as calorie intake, were measured. The metabolic changes such as obesity, dyslipidaemia, hypertension, and hyperglycaemia were determined. Data was presented in mean ± SEM subjected to one-way ANOVA. Results. Male Wistar rats fed with FDW 20% for eight weeks developed significant higher obesity parameters compared to those fed with FDW 25%. There was hypertrophy of adipocytes in F20 and F25. There were also systolic hypertension, hypertriglyceridemia, and hyperglycemia in both groups. Conclusion. We conclude that the metabolic syndrome rat model is best established with the induction of FDW 20% for eight weeks. This was evident in the form of higher obesity parameter which caused the development of the metabolic syndrome. PMID:25045660

Induction of autophagy improves embryo viability in cloned mouse embryos

PubMed Central

Shen, XingHui; Zhang, Na; Wang, ZhenDong; Bai, GuangYu; Zheng, Zhong; Gu, YanLi; Wu, YanShuang; Liu, Hui; Zhou, DongJie; Lei, Lei

2015-01-01

Autophagy is an essential cellular mechanism that degrades cytoplasmic proteins and organelles to recycle their components. Moreover, autophagy is essential for preimplantation development in mammals. Here we show that autophagy is also important for reprogramming in somatic cell nuclear transfer (SCNT). Our data indicate that unlike fertilized oocytes, autophagy is not triggered in SCNT embryos during 6 hours of activation. Mechanistically, the inhibited autophagic induction during SCNT activation is due to the cytochalasin B (CB) caused depolymerization of actin filaments. In this study, we induced autophagy during SCNT activation by rapamycin and pp242, which could restore the expected level of autophagy and significantly enhance the development of SCNT embryos to the blastocyst stage when compared with the control (68.5% and 68.7% vs. 41.5%, P < 0.05). Furthermore, the treatment of rapamycin and pp242 accelerates active DNA demethylation indicated by the conversion of 5 mC to 5 hmC, and treatment of rapamycin improves degradation of maternal mRNA as well. Thus, our findings reveal that autophagy is important for development of SCNT embryos and inhibited autophagic induction during SCNT activation might be one of the serious causes of low efficiency of SCNT. PMID:26643778

High-mobility group box 1 is an important mediator of microglial activation induced by cortical spreading depression.

PubMed

Takizawa, Tsubasa; Shibata, Mamoru; Kayama, Yohei; Shimizu, Toshihiko; Toriumi, Haruki; Ebine, Taeko; Unekawa, Miyuki; Koh, Anri; Yoshimura, Akihiko; Suzuki, Norihiro

2017-03-01

Single episodes of cortical spreading depression (CSD) are believed to cause typical migraine aura, whereas clusters of spreading depolarizations have been observed in cerebral ischemia and subarachnoid hemorrhage. We recently demonstrated that the release of high-mobility group box 1 (HMGB1) from cortical neurons after CSD in a rodent model is dependent on the number of CSD episodes, such that only multiple CSD episodes can induce significant HMGB1 release. Here, we report that only multiple CSD inductions caused microglial hypertrophy (activation) accompanied by a greater impact on the transcription activity of the HMGB1 receptor genes, TLR2 and TLR4, while the total number of cortical microglia was not affected. Both an HMGB1-neurtalizing antibody and the HMGB1 inhibitor glycyrrhizin abrogated multiple CSD-induced microglial hypertrophy. Moreover, multiple CSD inductions failed to induce microglial hypertrophy in TLR2/4 double knockout mice. These results strongly implicate the HMGB1-TLR2/4 axis in the activation of microglia following multiple CSD inductions. Increased expression of the lysosomal acid hydrolase cathepsin D was detected in activated microglia by immunostaining, suggesting that lysosomal phagocytic activity may be enhanced in multiple CSD-activated microglia.

Volatile Anesthetics Improve Survival after Cecal Ligation and Puncture

PubMed Central

Herrmann, Inge K.; Castellon, Maricela; Schwartz, David E.; Hasler, Melanie; Urner, Martin; Hu, Guochang; Minshall, Richard D.; Beck-Schimmer, Beatrice

2016-01-01

Background Sepsis remains a leading cause of death in intensive care units. There is growing evidence that volatile anesthetics have beneficial immunomodulatory effects on complex inflammation-mediated conditions. The authors investigated the effect of volatile anesthetics on the overall survival of mice in a sepsis model of cecal ligation and puncture (CLP). Methods Mice (N = 12 per treatment group) were exposed to anesthetic concentrations of desflurane, isoflurane, and sevoflurane either during induction of sepsis or when the mice showed pronounced symptoms of inflammation. Overall survival, as well as organ function and inflammation was compared with the CLP group without intervention. Results With desflurane and sevoflurane conditioning (1.2 minimal alveolar concentration for 2 h immediately after induction of CLP) overall survival was improved to 58% and 83%, respectively, compared with 17% in the untreated CLP group. Isoflurane did not significantly affect outcome. Application of sevoflurane 24 h after sepsis induction significantly improved overall survival to 66%. Conclusions Administration of the volatile anesthetics desflurane and sevoflurane reduced CLP-induced mortality. Anesthesia may be a critical confounder when comparing study data where different anesthesia protocols were used. PMID:23867232

Induction of labour for improving birth outcomes for women at or beyond term

PubMed Central

Gülmezoglu, A Metin; Crowther, Caroline A; Middleton, Philippa; Heatley, Emer

2014-01-01

Background As a pregnancy continues beyond term the risks of babies dying inside the womb or in the immediate newborn period increase. Whether a policy of labour induction at a predetermined gestational age can reduce this increased risk is the subject of this review. Objectives To evaluate the benefits and harms of a policy of labour induction at term or post-term compared with awaiting spontaneous labour or later induction of labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 March 2012). Selection criteria Randomised controlled trials conducted in women at or beyond term. The eligible trials were those comparing a policy of labour induction with a policy of awaiting spontaneous onset of labour. Cluster-randomised trials and cross-over trials are not included. Quasi-random allocation schemes such as alternation, case record numbers or open random-number lists were not eligible. Data collection and analysis Two review authors independently assessed trials for inclusion. Two review authors independently assessed trial quality and extracted data. Data were checked for accuracy. Outcomes are analysed in two main categories: gestational age and cervix status. Main results We included 22 trials reporting on 9383 women. The trials were generally at moderate risk of bias. Compared with a policy of expectant management, a policy of labour induction was associated with fewer (all-cause) perinatal deaths: risk ratio (RR) 0.31, 95% confidence interval (CI) 0.12 to 0.88; 17 trials, 7407 women. There was one perinatal death in the labour induction policy group compared with 13 perinatal deaths in the expectant management group. The number needed to treat to benefit (NNTB) with induction of labour in order to prevent one perinatal death was 410 (95% CI 322 to 1492). For the primary outcome of perinatal death and most other outcomes, no differences between timing of induction subgroups were seen; the majority of trials adopted a policy of induction at 41 completed weeks (287 days) or more. Fewer babies in the labour induction group had meconium aspiration syndrome (RR 0.50, 95% CI 0.34 to 0.73; eight trials, 2371 infants) compared with a policy of expectant management. There was no statistically significant difference between the rates of neonatal intensive care unit (NICU) admission for induction compared with expectant management (RR 0.90, 95% CI 0.78 to 1.04; 10 trials, 6161 infants). For women in the policy of induction arms of trials, there were significantly fewer caesarean sections compared with expectant management in 21 trials of 8749 women (RR 0.89, 95% CI 0.81 to 0.97). Authors’ conclusions A policy of labour induction compared with expectant management is associated with fewer perinatal deaths and fewer caesarean sections. Some infant morbidities such as meconium aspiration syndrome were also reduced with a policy of post-term labour induction although no significant differences in the rate of NICU admission were seen. However, the absolute risk of perinatal death is small. Women should be appropriately counselled in order to make an informed choice between scheduled induction for a post-term pregnancy or monitoring without induction (or delayed induction). PMID:22696345

Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity.

PubMed

Hirashima, Rika; Michimae, Hirofumi; Takemoto, Hiroaki; Sasaki, Aya; Kobayashi, Yoshinori; Itoh, Tomoo; Tukey, Robert H; Fujiwara, Ryoichi

2016-09-01

Anticonvulsants can increase the risk of developing neurotoxicity in infants; however, the underlying mechanism has not been elucidated to date. Thyroxine [3,5,3',5'-l-tetraiodothyronine (T4)] plays crucial roles in the development of the central nervous system. In this study, we hypothesized that induction of UDP-glucuronosyltransferase 1A1 (UGT1A1)-an enzyme involved in the metabolism of T4-by anticonvulsants would reduce serum T4 levels and cause neurodevelopmental toxicity. Exposure of mice to phenytoin during both the prenatal and postnatal periods significantly induced UGT1A1 and decreased serum T4 levels on postnatal day 14. In the phenytoin-treated mice, the mRNA levels of synaptophysin and synapsin I in the hippocampus were lower than those in the control mice. The thickness of the external granule cell layer was greater in phenytoin-treated mice, indicating that induction of UGT1A1 during the perinatal period caused neurodevelopmental disorders. Exposure to phenytoin during only the postnatal period also caused these neurodevelopmental disorders. A T4 replacement attenuated the increase in thickness of the external granule cell layer, indicating that the reduced T4 was specifically associated with the phenytoin-induced neurodevelopmental disorder. In addition, these neurodevelopmental disorders were also found in the carbamazepine- and pregnenolone-16-α-carbonitrile-treated mice. Our study is the first to indicate that UGT1A1 can control neurodevelopment by regulating serum T4 levels. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity

PubMed Central

Hirashima, Rika; Michimae, Hirofumi; Takemoto, Hiroaki; Sasaki, Aya; Kobayashi, Yoshinori; Itoh, Tomoo; Tukey, Robert H.

2016-01-01

Anticonvulsants can increase the risk of developing neurotoxicity in infants; however, the underlying mechanism has not been elucidated to date. Thyroxine [3,5,3′,5′-l-tetraiodothyronine (T4)] plays crucial roles in the development of the central nervous system. In this study, we hypothesized that induction of UDP-glucuronosyltransferase 1A1 (UGT1A1)—an enzyme involved in the metabolism of T4—by anticonvulsants would reduce serum T4 levels and cause neurodevelopmental toxicity. Exposure of mice to phenytoin during both the prenatal and postnatal periods significantly induced UGT1A1 and decreased serum T4 levels on postnatal day 14. In the phenytoin-treated mice, the mRNA levels of synaptophysin and synapsin I in the hippocampus were lower than those in the control mice. The thickness of the external granule cell layer was greater in phenytoin-treated mice, indicating that induction of UGT1A1 during the perinatal period caused neurodevelopmental disorders. Exposure to phenytoin during only the postnatal period also caused these neurodevelopmental disorders. A T4 replacement attenuated the increase in thickness of the external granule cell layer, indicating that the reduced T4 was specifically associated with the phenytoin-induced neurodevelopmental disorder. In addition, these neurodevelopmental disorders were also found in the carbamazepine- and pregnenolone-16-α-carbonitrile–treated mice. Our study is the first to indicate that UGT1A1 can control neurodevelopment by regulating serum T4 levels. PMID:27413119

Induction of heme oxygenase-1 by chamomile protects murine macrophages against oxidative stress.

PubMed

Bhaskaran, Natarajan; Shukla, Sanjeev; Kanwal, Rajnee; Srivastava, Janmejai K; Gupta, Sanjay

2012-06-27

Protection of cells from oxidative insult may be possible through direct scavenging of reactive oxygen species, or through stimulation of intracellular antioxidant defense mechanisms by induction of antioxidant gene expression. In this study we investigated the cytoprotective effect of chamomile and elucidated the underlying mechanisms. The cytoprotective effect of chamomile was examined on H(2)O(2)-induced cellular stress in RAW 264.7 murine macrophages. RAW 264.7 murine macrophages treated with chamomile were protected from cell death caused by H(2)O(2). Treatment with 50μM H(2)O(2) for 6h caused significant increase in cellular stress accompanied by cell death in RAW 264.7 macrophages. Pretreatment with chamomile at 10-20μg/mL for 16h followed by H(2)O(2) treatment protected the macrophages against cell death. Chamomile exposure significantly increased the expression of antioxidant enzymes viz. heme oxygenase-1 (HO-1), peroxiredoxin-1 (Prx-1), and thioredoxin-1 (Trx-1) in a dose-dependent manner, compared with their respective controls. Chamomile increased nuclear translocation of Nrf2 with increased phosphorylated Nrf2 levels, and binding to the antioxidant response element in the nucleus. These molecular findings for the first time provide insights into the mechanisms underlying the induction of phase 2 enzymes through the Keap1-Nrf2 signaling pathway by chamomile, and provide evidence that chamomile possesses antioxidant and cytoprotective properties. Copyright © 2012 Elsevier Inc. All rights reserved.

Planarian D-amino acid oxidase is involved in ovarian development during sexual induction.

PubMed

Maezawa, Takanobu; Tanaka, Hiroyuki; Nakagawa, Haruka; Ono, Mizuki; Aoki, Manabu; Matsumoto, Midori; Ishida, Tetsuo; Horiike, Kihachiro; Kobayashi, Kazuya

2014-05-01

To elucidate the molecular mechanisms underlying switching from asexual to sexual reproduction, namely sexual induction, we developed an assay system for sexual induction in the hermaphroditic planarian species Dugesia ryukyuensis. Ovarian development is the initial and essential step in sexual induction, and it is followed by the formation of other reproductive organs, including the testes. Here, we report a function of a planarian D-amino acid oxidase, Dr-DAO, in the control of ovarian development in planarians. Asexual worms showed significantly more widespread expression of Dr-DAO in the parenchymal space than did sexual worms. Inhibition of Dr-DAO by RNAi caused the formation of immature ovaries. In addition, we found that feeding asexual worms 5 specific D-amino acids could induce the formation of immature ovaries that are similar to those observed in Dr-DAO knockdown worms, suggesting that Dr-DAO inhibits the formation of immature ovaries by degrading these D-amino acids. Following sexual induction, Dr-DAO expression was observed in the ovaries. The knockdown of Dr-DAO during sexual induction delayed the maturation of the other reproductive organs, as well as ovary. These findings suggest that Dr-DAO acts to promote ovarian maturation and that complete sexual induction depends on the production of mature ovaries. We propose that Dr-DAO produced in somatic cells prevents the onset of sexual induction in the asexual state, and then after sexual induction, the female germ cells specifically produce Dr-DAO to induce full maturation. Therefore, Dr-DAO produced in somatic and female germline cells may play different roles in sexual induction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Induction of skin papillomas in the rabbit, Oryctologus cuniculus, by bites of a blood-sucking insect, Cimex lectularius, irradiated by gamma rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

el-Mofty, M.M.; Sakr, S.A.; Younis, M.W.

Bed bugs, Cimex lectularius, irradiated with gamma rays were allowed to suck blood from shaved areas of the skin of rabbits, Oryctolagus cuniculus, 2 times/week for 5 months and then once weekly for another 5 months. This significantly induced the formation of skin papillomas and sweat gland hyperplasia in five out of nine experimental animals. It is speculated that the saliva of the irradiated bugs was activated by gamma rays and was responsible for the induction of skin papillomas. Because bed bugs play a significant role in the transmission of virus, it is also speculated that there is a virusmore » in the saliva of bugs; this virus may be activated by gamma radiation and causes the development of papillomas in the skin.« less

Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer.

PubMed

Ahn, Peter H; Machtay, Mitchell; Anne, Pramila R; Cognetti, David; Keane, William M; Wuthrick, Evan; Dicker, Adam P; Axelrod, Rita S

2018-05-01

Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned. Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease. Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.

Sufficiency and Necessity Assumptions in Causal Structure Induction

ERIC Educational Resources Information Center

Mayrhofer, Ralf; Waldmann, Michael R.

2016-01-01

Research on human causal induction has shown that people have general prior assumptions about causal strength and about how causes interact with the background. We propose that these prior assumptions about the parameters of causal systems do not only manifest themselves in estimations of causal strength or the selection of causes but also when…

Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy.

PubMed

Di Pietro, C; Piro, S; Tabbì, G; Ragusa, M; Di Pietro, V; Zimmitti, V; Cuda, F; Anello, M; Consoli, U; Salinaro, E T; Caruso, M; Vancheri, C; Crimi, N; Sabini, M G; Cirrone, G A P; Raffaele, L; Privitera, G; Pulvirenti, A; Giugno, R; Ferro, A; Cuttone, G; Lo Nigro, S; Purrello, R; Purrello, F; Purrello, M

2006-01-01

Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.

A study of carburetor/induction system icing in general aviation accidents

NASA Technical Reports Server (NTRS)

Obermayer, R. W.; Roe, W. T.

1975-01-01

An assessment of the frequency and severity of carburetor/induction icing in general-aviation accidents was performed. The available literature and accident data from the National Transportation Safety Board were collected. A computer analysis of the accident data was performed. Between 65 and 90 accidents each year involve carburetor/induction system icing as a probable cause/factor. Under conditions conducive to carburetor/induction icing, between 50 and 70 percent of engine malfunction/failure accidents (exclusive of those due to fuel exhaustion) are due to carburetor/induction system icing. Since the evidence of such icing may not remain long after an accident, it is probable that the frequency of occurrence of such accidents is underestimated; therefore, some extrapolation of the data was conducted. The problem of carburetor/induction system icing is particularly acute for pilots with less than 1000 hours of total flying time. The severity of such accidents is about the same as any accident resulting from a forced landing or precautionary landing. About 144 persons, on the average, are exposed to death and injury each year in accidents involving carburetor/induction icing as a probable cause/factor.

Induction prednisone dosing for childhood nephrotic syndrome: how low should we go?

PubMed

Sibley, Matthew; Roshan, Abishek; Alshami, Alanoud; Catapang, Marisa; Jöbsis, Jasper J; Kwok, Trevor; Polderman, Nonnie; Sibley, Jennifer; Matsell, Douglas G; Mammen, Cherry

2018-05-22

Historically, children with nephrotic syndrome (NS) across British Columbia (BC), Canada have been cared for without formal standardization of induction prednisone dosing. We hypothesized that local historical practice variation in induction dosing was wide and that children treated with lower doses had worse relapsing outcomes. This retrospective cohort study included 92 NS patients from BC Children's Hospital (1990-2010). We excluded secondary causes of NS, age < 1 year at diagnosis, steroid resistance, and incomplete induction due to early relapse. We explored cumulative induction dose and defined dosing quartiles. Relapsing outcomes above and below each quartile threshold were compared including total relapses in 2 years, time to first relapse, and proportions developing frequently relapsing NS (FRNS) or starting a steroid-sparing agent (SSA). Cumulative prednisone was widely distributed with approximated median, 1st, and 3rd quartile doses of 2500, 2000, and 3000 mg/m 2 respectively. Doses ≤ 2000 mg/m 2 showed significantly higher relapses (4.2 vs 2.7), shorter time to first relapse (61 vs 175 days), and higher SSA use (36 vs 14%) compared to higher doses. Doses ≤ 2500 mg/m 2 also showed significantly more relapses (3.9 vs 2.2), quicker first relapse (79 vs 208 days), and higher FRNS (37 vs 17%) and SSA use (28 vs 11%). Relapsing outcomes lacked statistical difference in ≤ 3000 vs > 3000 mg/m 2 doses. Results strongly justify our development of a standardized, province-wide NS clinical pathway to reduce practice variation and minimize under-treatment. The lowest induction prednisone dosing threshold to minimize future relapsing risks is likely between 2000 and 2500 mg/m 2 . Further prospective studies are warranted.

Treatment of pleural malignancies by photo-induction combined to systemic chemotherapy: Proof of concept on rodent lung tumors and feasibility study on porcine chest cavities.

PubMed

Wang, Xingyu; Gronchi, Fabrizio; Bensimon, Michael; Mercier, Thomas; Decosterd, Laurent Arthur; Wagnières, Georges; Debefve, Elodie; Ris, Hans-Beat; Letovanec, Igor; Peters, Solange; Perentes, Jean Yannis

2015-12-01

Low-dose, Visudyne®-mediated photodynamic therapy (photo-induction) was shown to selectively enhance tumor vessel transport causing increased uptake of systemically administered chemotherapy in various tumor types grown on rodent lungs. The present experiments explore the efficacy of photo-induced vessel modulation combined to intravenous (IV) liposomal cisplatin (Lipoplatin®) on rodent lung tumors and the feasibility/toxicity of this approach in porcine chest cavities. Three groups of Fischer rats underwent orthotopic sarcoma (n = 14), mesothelioma (n = 14), or adenocarcinoma (n = 12) implantation on the left lung. Half of the animals of each group had photo-induction (0.0625 mg/kg Visudyne®, 10 J/cm(2) ) followed by IV administration of Lipoplatin® (5 mg/kg) and the other half received Lipoplatin® without photo-induction. Then, two groups of minipigs underwent intrapleural thoracoscopic (VATS) photo-induction (0.0625 mg/kg Visudyne®; 30 J/cm(2) hilum; 10 J/cm(2) apex/diaphragm) with in situ light dosimetry in combination with IV Lipoplatin® administration (5 mg/kg). Protocol I (n = 6) received Lipoplatin® immediately after light delivery and Protocol II (n = 9) 90 minutes before light delivery. Three additional animals received Lipoplatin® and VATS pleural biopsies but no photo-induction (controls). Lipoplatin® concentrations were analyzed in blood and tissues before and at regular intervals after photo-induction using inductively coupled plasma mass spectrometry. Photo-induction selectively increased Lipoplatin® uptake in all orthotopic tumors. It significantly increased the ratio of tumor to lung Lipoplatin® concentration in sarcoma (P = 0.0008) and adenocarcinoma (P = 0.01) but not in mesothelioma, compared to IV drug application alone. In minipigs, intrapleural photo-induction combined to systemic Lipoplatin® was well tolerated with no toxicity at 7 days for both treatment protocols. The pleural Lipoplatin® concentrations were not significantly different at 10 and 30 J/cm(2) locations but they were significantly higher in protocol I compared to II (2.37 ± 0.7 vs. 1.37 ± 0.7 ng/mg, P  < 0.001). Visudyne®-mediated photo-induction selectively enhances the uptake of IV administered Lipoplatin® in rodent lung tumors. Intrapleural VATS photo-induction with identical treatment conditions combined to IV Lipoplatin chemotherapy is feasible and well tolerated in a porcine model. Lasers Surg. Med. 47:807-816, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

[The influence of application of a low-frequency magnetic field on the serum corticosterone level (an experimental study)].

PubMed

Alabovskiĭ, V V; Gotovskiĭ, M Iu; Vinokurov, A A; Maslov, O V

2013-01-01

The results of analysis of the literature publications suggest the necessity of experimental studies aimed at investigation of modulating effect of low-frequency magnetic fields on endocrine organs. The present study was carried out using 200 outbred white male rats (body weight 200-220 g). Corticosterone was measured in blood sera following the application of a low-frequency magnetic field (20 and 53 Hz with induction from 0.4 to 6 mT) generated by a Mini-Expert-T apparatus for induction magnetic therapy during 30 minutes. It was shown that the application of the alternating magnetic field to the adrenal region of the rats in the selected frequency and induction ranges caused a significant increase in the serum corticosterone levels. The results of the present study on the hormonal activity of rat adrenals give reason to consider the influence of the alternating magnetic fields as being modulatory. Analysis of the data thus obtained has demonstrated the non-linear dependence of glucocorticoid activity of the rat adrenal glands on the induction strength of the alternating magnetic field.

Oxidative alterations induced by D-aspartic acid in prepubertal rat testis in vitro: a mechanistic study.

PubMed

Chandrashekar, K N; Muralidhara

2008-07-01

The objective of the present study was to investigate the oxidative induction response following in vitro treatment with D-aspartic acid (DA) in prepubertal rat testis (homogenates, explants, and cell suspensions). In all three preparations, DA enhanced (P<0.001) lipid peroxidation, manifest as increased reactive oxygen species (ROS) and malondialdehyde (MDA). Further, DA-induced oxidative induction was potentiated (P<0.001) in the presence of iron (5 microM) and 3-amino triazole and mercaptosuccinate (P<0.001), known inhibitors of the peroxide metabolizing enzymes, catalase and glutathione peroxidase, respectively. Testis homogenates exposed to L-arginine (LA) per se had reduced (P<0.001) endogenous levels of ROS and MDA; furthermore, pre-incubation with L-arginine markedly suppressed (P<0.001) DA-induced oxidative induction, suggesting an antagonistic action, perhaps due to LA-derived nitric oxide. In conclusion, DA caused significant oxidative induction in prepubertal rat testis, but this action was abrogated by L-arginine. The relevance of this phenomenon in vivo merits further study, as both of these molecules have specific physiological functions in the testis.

Lack of photoprotection against UVB-induced erythema by immediate pigmentation induced by 382 nm radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Black, G.; Matzinger, E.; Gange, R.W.

Immediate pigment darkening (IPD) was induced on the backs of 11 human volunteers of skin types III and IV by exposing the skin to UVA radiation (382 nm). The minimum erythema dose (MED) of UVB radiation was also determined by exposing sites to graduated doses of 304 nm radiation. The order of exposure of distinct anatomic areas was as follow: UVB followed by IPD induction; IPD induction followed by UVB; IPD induction followed 3 h later by UVB; and UVB only. Erythema responses induced by UVB were graded by inspection 24 h later and the MEDs in the 4 areasmore » were compared. The induction of IPD before UVB exposure caused no significant change in the MED compared to sites receiving UVB only, or receiving UVA radiation after UVB, confirming that the IPD reaction does not protect against UVB-induced erythema. There was also no evidence of photorecovery, i.e., an increase in the MED of UVB resulting from exposure to longer wavelength, UV or visible radiation following UVB exposure.« less

[Quantitative Prediction of Drug-Drug Interaction Caused by CYP Inhibition and Induction from In Vivo Data and Its Application in Daily Clinical Practices-Proposal for the Pharmacokinetic Interaction Significance Classification System (PISCS)].

PubMed

Ohno, Yoshiyuki

2018-01-01

　Drug-drug interactions (DDIs) can affect the clearance of various drugs from the body; however, these effects are difficult to sufficiently evaluate in clinical studies. This article outlines our approach to improving methods for evaluating and providing drug information relative to the effects of DDIs. In a previous study, total exposure changes to many substrate drugs of CYP caused by the co-administration of inhibitor or inducer drugs were successfully predicted using in vivo data. There are two parameters for the prediction: the contribution ratio of the enzyme to oral clearance for substrates (CR), and either the inhibition ratio for inhibitors (IR) or the increase in clearance of substrates produced by induction (IC). To apply these predictions in daily pharmacotherapy, the clinical significance of any pharmacokinetic changes must be carefully evaluated. We constructed a pharmacokinetic interaction significance classification system (PISCS) in which the clinical significance of DDIs was considered in a systematic manner, according to pharmacokinetic changes. The PISCS suggests that many current 'alert' classifications are potentially inappropriate, especially for drug combinations in which pharmacokinetics have not yet been evaluated. It is expected that PISCS would contribute to constructing a reliable system to alert pharmacists, physicians and consumers of a broad range of pharmacokinetic DDIs in order to more safely manage daily clinical practices.

The Alternative Epac/cAMP Pathway and the MAPK Pathway Mediate hCG Induction of Leptin in Placental Cells

PubMed Central

Maymó, Julieta Lorena; Pérez Pérez, Antonio; Maskin, Bernardo; Dueñas, José Luis; Calvo, Juan Carlos; Sánchez Margalet, Víctor; Varone, Cecilia Laura

2012-01-01

Pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in the placenta, where it works as an autocrine hormone. In this work, we demonstrated that human chorionic gonadotropin (hCG) added to JEG-3 cell line or to placental explants induces endogenous leptin expression. We also found that hCG increased cAMP intracellular levels in BeWo cells in a dose-dependent manner, stimulated cAMP response element (CRE) activity and the cotransfection with an expression plasmid of a dominant negative mutant of CREB caused a significant inhibition of hCG stimulation of leptin promoter activity. These results demonstrate that hCG indeed activates cAMP/PKA pathway, and that this pathway is involved in leptin expression. Nevertheless, we found leptin induction by hCG is dependent on cAMP levels. Treatment with (Bu)2cAMP in combination with low and non stimulatory hCG concentrations led to an increase in leptin expression, whereas stimulatory concentrations showed the opposite effect. We found that specific PKA inhibition by H89 caused a significant increase of hCG leptin induction, suggesting that probably high cAMP levels might inhibit hCG effect. It was found that hCG enhancement of leptin mRNA expression involved the MAPK pathway. In this work, we demonstrated that hCG leptin induction through the MAPK signaling pathway is inhibited by PKA. We observed that ERK1/2 phosphorylation increased when hCG treatment was combined with H89. In view of these results, the involvement of the alternative cAMP/Epac signaling pathway was studied. We observed that a cAMP analogue that specifically activates Epac (CPT-OMe) stimulated leptin expression by hCG. In addition, the overexpression of Epac and Rap1 proteins increased leptin promoter activity and enhanced hCG. In conclusion, we provide evidence suggesting that hCG induction of leptin gene expression in placenta is mediated not only by activation of the MAPK signaling pathway but also by the alternative cAMP/Epac signaling pathway. PMID:23056265

Angiotensin II Causes Neuronal Damage in Stretch-Injured Neurons: Protective Effects of Losartan, an Angiotensin T1 Receptor Blocker.

PubMed

Abdul-Muneer, P M; Bhowmick, Saurav; Briski, Nicholas

2017-11-08

Angiotensin II (Ang II) is a mediator of oxidative stress via activation/induction of reactive oxygen and nitrogen species-generating enzymes, NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS). We investigated the hypothesis that overproduction of Ang II during traumatic brain injury (TBI) induces the activation of the oxidative stress, which triggers neuroinflammation and cell apoptosis in a cell culture model of neuronal stretch injury. We first established that stretch injury causes a rapid increase in the level of Ang II, which causes the release of pro-inflammatory cytokines, IL-1β and TNF-α, via the induction of oxidative stress. Since angiotensin-converting enzyme (ACE) mediates the production of Ang II via the conversion of Ang I into Ang II, we analyzed the expression of ACE by western blotting. Further, we analyzed caspase-3-mediated apoptosis by TUNEL staining and annexin V western blotting. Angiotensin type I (AT 1 ) receptor antagonist losartan attenuated Ang II-induced oxidative stress and associated neuroinflammation and cell death in cultured neurons. Remarkably, we noticed that the expression of Ang II type 1 receptor (AngT 1 R) upregulated in neuronal stretch injury; losartan mitigates this upregulation. Findings from this study significantly extend our understanding of the pathophysiology of TBI and may have significant implications for developing therapeutic strategies for TBI-associated brain dysfunctions.

The discovery of the causes of leprosy: A computational analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corruble, V.; Ganascia, J.G.

1996-12-31

The role played by the inductive inference has been studied extensively in the field of Scientific Discovery. The work presented here tackles the problem of induction in medical research. The discovery of the causes of leprosy is analyzed and simulated using computational means. An inductive algorithm is proposed, which is successful in simulating some essential steps in the progress of the understanding of the disease. It also allows us to simulate the false reasoning of previous centuries through the introduction of some medical a priori inherited form archaic medicine. Corroborating previous research, this problem illustrates the importance of the socialmore » and cultural environment on the way the inductive inference is performed in medicine.« less

[The participation of ethanol in induction of carbohydrates metabolism disturbances].

PubMed

Orywal, Karolina; Jelski, Wojciech; Szmitkowski, Maciej

2009-07-01

Alcohol and products of its metabolism lead to impairment of many organs functions, what cause systemic and local carbohydrates metabolism disturbances. Abusing of alcohol induces changes in pancreatic digestive enzymes secretion, what contributes to development of chronic alcoholic pancreatitis. Alcohol can cause secondary diabetes, what is result of pancreatic beta-cells damage and is a risk factor for type 2 diabetes. Alcohol cause liver cells degeneration and induction of many metabolic disturbances especially carbohydrates.

Fagopyrum tataricum (Buckwheat) Improved High-Glucose-Induced Insulin Resistance in Mouse Hepatocytes and Diabetes in Fructose-Rich Diet-Induced Mice

PubMed Central

Lee, Chia-Chen; Hsu, Wei-Hsuan; Shen, Siou-Ru; Cheng, Yu-Hsiang; Wu, She-Ching

2012-01-01

Fagopyrum tataricum (buckwheat) is used for the treatment of type 2 diabetes mellitus in Taiwan. This study was to evaluate the antihyperglycemic and anti-insulin resistance effects of 75% ethanol extracts of buckwheat (EEB) in FL83B hepatocytes by high-glucose (33 mM) induction and in C57BL/6 mice by fructose-rich diet (FRD; 60%) induction. The active compounds of EEB (100 μg/mL; 50 mg/kg bw), quercetin (6 μg/mL; 3 mg/kg bw), and rutin (23 μg/mL; 11.5 mg/kg bw) were also employed to treat FL83B hepatocytes and animal. Results indicated that EEB, rutin, and quercetin + rutin significantly improved 2-NBDG uptake via promoting Akt phosphorylation and preventing PPARγ degradation caused by high-glucose induction for 48 h in FL83B hepatocytes. We also found that EEB could elevate hepatic antioxidant enzymes activities to attenuate insulin resistance as well as its antioxidation caused by rutin and quercetin. Finally, EEB also inhibited increases in blood glucose and insulin levels of C57BL/6 mice induced by FRD. PMID:22548048

Differential expression analysis of genes involved in high-temperature induced sex differentiation in Nile tilapia.

PubMed

Li, Chun Ge; Wang, Hui; Chen, Hong Ju; Zhao, Yan; Fu, Pei Sheng; Ji, Xiang Shan

2014-01-01

Nowadays, high temperature effects on the molecular pathways during sex differentiation in teleosts need to be deciphered. In this study, a systematic differential expression analysis of genes involved in high temperature-induced sex differentiation was done in the Nile tilapia gonad and brain. Our results showed that high temperature caused significant down-regulation of CYP19A1A in the gonad of both sexes in induction group, and FOXL2 in the ovary of the induction group. The expressions of GTHα, LHβ and ERα were also significantly down-regulated in the brain of both sexes in the induction and recovery groups. On the contrary, the expression of CYP11B2 was significantly up-regulated in the ovary, but not in the testis in both groups. Spearman rank correlation analysis showed that there are significant correlations between the expressions of CYP19A1A, FOXL2, or DMRT1 in the gonads and the expression of some genes in the brain. Another result in this study showed that high temperature up-regulated the expression level of DNMT1 in the testis of the induction group, and DNMT1 and DNMT3A in the female brain of both groups. The expression and correlation analysis of HSPs showed that high temperature action on tilapia HSPs might indirectly induce the expression changes of sex differentiation genes in the gonads. These findings provide new insights on TSD and suggest that sex differentiation related genes, heat shock proteins, and DNA methylation genes are new candidates for studying TSD in fish species. Copyright © 2014 Elsevier Inc. All rights reserved.

Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models

PubMed Central

Barmada, Sami J.; Serio, Andrea; Arjun, Arpana; Bilican, Bilada; Daub, Aaron; Ando, D. Michael; Tsvetkov, Andrey; Pleiss, Michael; Li, Xingli; Peisach, Daniel; Shaw, Christopher; Chandran, Siddharthan; Finkbeiner, Steven

2014-01-01

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have distinct clinical features but a common pathology—cytoplasmic inclusions rich in TDP43. Rare TDP43 mutations cause ALS or FTD, but abnormal TDP43 levels and localization may cause disease even if TDP43 lacks a mutation. Here we showed that individual neurons vary in their ability to clear TDP43 and are exquisitely sensitive to TDP43 levels. To measure TDP43 clearance, we developed and validated a single-cell optical method that overcomes the confounding effects of aggregation and toxicity, and discovered that pathogenic mutations significantly shorten TDP43 half-life. Novel compounds that stimulate autophagy improved TDP43 clearance and localization, and enhanced survival in primary murine neurons and in human stem cell–derived neurons and astrocytes harboring mutant TDP43. These findings indicate that the levels and localization of TDP43 critically determine neurotoxicity and show that autophagy induction mitigates neurodegeneration by acting directly on TDP43 clearance. PMID:24974230

Cytotoxic effect of fenitrothion and lambda-cyhalothrin mixture on lipid peroxidation and antioxidant defense system in rat kidney.

PubMed

El-Demerdash, Fatma M

2012-01-01

A mixture of pyrethroids plus organophosphates was assessed for their potential effects on lipid peroxidation, the antioxidant defense system and lactate dehydrogenase (LDH) in rat kidney in vitro. Various insecticide concentrations were incubated with kidney homogenate at 37°C for different incubation times. Treatment with fenitothion (FNT) plus lambda-cyhalothrin (LC) caused a significant induction (P < 0.05) in thiobarbituric acid reactive substances (TBARS), which might be associated to decreased levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) activities and protein content in rat kidney. However, a significant induction of lactate dehydrogenase (LDH) activity was observed. The effect was concentration and time dependent. It can be concluded that depletion of GSH might indicate that reactive oxygen species (ROS) could be involved in the toxic effects of FNT plus LC which lead to marked perturbations in antioxidant defense system.

A comparison of midazolam with remifentanil for the prevention of myoclonic movements following etomidate injection.

PubMed

Hwang, J-Y; Kim, J-H; Oh, A-Y; Do, S-H; Jeon, Y-T; Han, S-H

2008-01-01

Etomidate is a popular anaesthetic induction agent, but it frequently causes myoclonic movements. Although both benzodiazepines and opioids reduce myoclonus, there has been no comparative study between these agents. Thus, we conducted a prospective, randomized study to compare midazolam and remifentanil as pre-treatment agents for reducing etomidate-induced myoclonus in 90 adults undergoing surgery. Patients were pre-treated before the etomidate injection, either with saline (Group C), midazolam 0.5 mg/kg (Group M) or remifentanil 1 microg/kg (Group R). Both Groups M and R showed a significantly lower incidence of myoclonus compared with Group C (17%, 17% and 77%, respectively). The incidence of myoclonus was not significantly different between Groups M and R, but 10% (n = 10) of the patients in Group R experienced remifentanil-related side-effects. We conclude that midazolam is probably a better choice than remifentanil for reducing etomidate-induced myoclonus during anaesthesia induction.

Inhibition and induction of aromatase (CYP19) activity by brominated flame retardants in H295R human adrenocortical carcinoma cells.

PubMed

Cantón, Rocío F; Sanderson, J Thomas; Letcher, Robert J; Bergman, Ake; van den Berg, Martin

2005-12-01

Brominated flame retardants (BFRs) are persistent and ubiquitous chemicals in the environment, and they are found at increasing levels in tissues of wildlife and humans. Previous in vitro studies with the BFR class of polybrominated diphenyl ethers (BDEs) have shown endocrine-disrupting properties. Our study assessed the potential effects of nineteen BDEs, five hydroxylated BDEs (OH-BDEs), one methoxylated BDE (CH(3)O-BDE), tetrabromobisphenol-A (TBBPA), its dibromopropane ether derivative (TBBPA-DBPE), and the brominated phenols/anisols 2,4,6-tribromophenol (TBP), 4-bromophenol (4BP) and 2,4,6-tribromoanisole (TBA) on the catalytic activity of the steroidogenic enzyme aromatase (CYP19) in H295R human adrenocortical carcinoma cells. Effects were studied in the concentration range from 0.5 to 7.5 microM; exposures were for 24 h. Both 6-OH-BDE47 and 6-OH-BDE99 showed an inhibitory effect on aromatase activity at concentrations >2.5 microM and >5 microM, respectively. However, 6-OH-BDE47 also caused a statistically significant increase in cytotoxicity (based on mitochondrial MTT reduction and lactate dehydrogenase-leakage [LDH]) at concentrations >2.5 microM that could explain in part the apparent inhibitory effect on aromatase activity. Compared to 6-OH-BDE47, the methoxy analog (6-CH(3)O-BDE47) did not elicit a cytotoxic effect, whereas significant inhibition of aromatase remained. TBP caused a concentration-dependent induction of aromatase activity between 0.5 and 7.5 microM (with a maximum of 3.8-fold induction at 7.5 microM). This induction was not observed when a OH- group replaced the CH(3)O- group or when bromine atoms adjacent to this OH- group were absent. These in vitro results provide a basis for studies of more detailed structure-activity relationships between these brominated compounds and the modulation of aromatase activity.

Pure non-dioxin-like PCB congeners suppress induction of AhR-dependent endpoints in rat liver cells.

PubMed

Brenerová, Petra; Hamers, Timo; Kamstra, Jorke H; Vondráček, Jan; Strapáčová, Simona; Andersson, Patrik L; Machala, Miroslav

2016-02-01

The relative potencies of non-ortho-substituted coplanar polychlorinated biphenyl (PCB) congeners to activate the aryl hydrocarbon receptor (AhR) and to cause the AhR-dependent toxic events are essential for their risk assessment. Since some studies suggested that abundant non-dioxin-like PCB congeners (NDL-PCBs) may alter the AhR activation by PCB mixtures and possibly cause non-additive effects, we evaluated potential suppressive effects of NDL-PCBs on AhR activation, using a series of 24 highly purified NDL-PCBs. We investigated their impact on the model AhR agonist-induced luciferase reporter gene expression in rat hepatoma cells and on induction of CYP1A1/1B1 mRNAs and deregulation of AhR-dependent cell proliferation in rat liver epithelial cells. PCBs 128, 138, and 170 significantly suppressed AhR activation (with IC50 values from 1.4 to 5.6 μM), followed by PCBs 28, 47, 52, and 180; additionally, PCBs 122, 153, and 168 showed low but still significant potency to reduce luciferase activity. Detection of CYP1A1 mRNA levels in liver epithelial cells largely confirmed these results for the most abundant NDL-PCBs, whereas the other AhR-dependent events (CYP1B1 mRNA expression, induction of cell proliferation in confluent cells) were less sensitive to NDL-PCBs, thus indicating a more complex regulation of these endpoints. The present data suggest that some NDL-PCBs could modulate overall dioxin-like effects in complex mixtures.

Evaluation of liposome-encapsulated butorphanol tartrate for alleviation of experimentally induced arthritic pain in green-cheeked conures (Pyrrhura molinae)

PubMed Central

Paul-Murphy, Joanne R.; Krugner-Higby, Lisa A.; Tourdot, Renee L.; Sladky, Kurt K.; Klauer, Julia M.; Keuler, Nicholas S.; Brown, Carolyn S.; Heath, Timothy D.

2014-01-01

Objective To evaluate injection of microcrystalline sodium urate (MSU) for inducing articular pain in green-cheeked conures (Pyrrhura molinae) and the analgesic efficacy of liposome-encapsulated butorphanol tartrate (LEBT) by use of weight load data, behavioral scores, and fecal corticosterone concentration. Animals 8 conures. Procedures In a crossover study, conures were randomly assigned to receive LEBT (15 mg/kg) or liposomal vehicle subsequent to experimental induction of arthritis or sham injection. The MSU was injected into 1 tibiotarsal-tarsometatarsal (intertarsal) joint to induce arthritis (time 0). Weight-bearing load and behavioral scores were determined at 0, 2, 6, 26, and 30 hours. Results MSU injection into 1 intertarsal joint caused a temporary decrease in weight bearing on the affected limb. Treatment of arthritic conures with LEBT resulted in significantly more weight bearing on the arthritic limb than treatment with vehicle. Administration of vehicle to arthritic conures caused a decrease in activity and feeding behaviors during the induction phase of arthritis, but as the arthritis resolved, there was a significant increase in voluntary activity at 30 hours and feeding behaviors at 26 and 30 hours, compared with results for LEBT treatment of arthritic birds. Treatment with LEBT or vehicle in conures without arthritis resulted in similar measurements for weight bearing and voluntary and motivated behaviors. Conclusions and Clinical Relevance Experimental induction of arthritis in conures was a good method for evaluating tonic pain. Weight-bearing load was the most sensitive measure of pain associated with induced arthritis. Pain associated with MSU-induced arthritis was alleviated by administration of LEBT. PMID:19795935

GABAergic Neurotransmission in the Pontine Reticular Formation Modulates Hypnosis, Immobility, and Breathing during Isoflurane Anesthesia

PubMed Central

Vanini, Giancarlo; Watson, Christopher J.; Lydic, Ralph; Baghdoyan, Helen A.

2009-01-01

Background Many general anesthetics are thought to produce a loss of wakefulness, in part, by enhancing gamma-aminobutyric acid (GABA) neurotransmission. However, GABAergic neurotransmission in the pontine reticular formation promotes wakefulness. This study tested the hypotheses that: 1) relative to wakefulness, isoflurane decreases GABA levels in the pontine reticular formation; and 2) pontine reticular formation administration of drugs that increase or decrease GABA levels increases or decreases, respectively, isoflurane induction time. Methods To test hypothesis 1, cats (n = 5) received a craniotomy and permanent electrodes for recording the electroencephalogram and electromyogram. Dialysis samples were collected from the pontine reticular formation during isoflurane anesthesia and wakefulness. GABA levels were quantified using high performance liquid chromatography. For hypothesis 2, rats (n = 10) were implanted with a guide cannula aimed for the pontine reticular formation. Each rat received microinjections of Ringer’s (vehicle control), the GABA uptake inhibitor nipecotic acid, and the GABA synthesis inhibitor 3-mercaptopropionic acid. Rats were then anesthetized with isoflurane and induction time was quantified as loss of righting reflex. Breathing rate was also measured. Results Relative to wakefulness, GABA levels were significantly decreased by isoflurane. Increased power in the electroencephalogram and decreased activity in the electromyogram caused by isoflurane co-varied with pontine reticular formation GABA levels. Nipecotic acid and 3-mercaptopropionic acid significantly increased and decreased, respectively, isoflurane induction time. Nipecotic acid also increased breathing rate. Conclusion Decreasing pontine reticular formation GABA levels comprises one mechanism by which isoflurane causes loss of consciousness, altered cortical excitability, muscular hypotonia, and decreased respiratory rate. PMID:19034094

Gamma-aminobutyric acid-mediated neurotransmission in the pontine reticular formation modulates hypnosis, immobility, and breathing during isoflurane anesthesia.

PubMed

Vanini, Giancarlo; Watson, Christopher J; Lydic, Ralph; Baghdoyan, Helen A

2008-12-01

Many general anesthetics are thought to produce a loss of wakefulness, in part, by enhancing gamma-aminobutyric acid (GABA) neurotransmission. However, GABAergic neurotransmission in the pontine reticular formation promotes wakefulness. This study tested the hypotheses that (1) relative to wakefulness, isoflurane decreases GABA levels in the pontine reticular formation; and (2) pontine reticular formation administration of drugs that increase or decrease GABA levels increases or decreases, respectively, isoflurane induction time. To test hypothesis 1, cats (n = 5) received a craniotomy and permanent electrodes for recording the electroencephalogram and electromyogram. Dialysis samples were collected from the pontine reticular formation during isoflurane anesthesia and wakefulness. GABA levels were quantified using high-performance liquid chromatography. For hypothesis 2, rats (n = 10) were implanted with a guide cannula aimed for the pontine reticular formation. Each rat received microinjections of Ringer's (vehicle control), the GABA uptake inhibitor nipecotic acid, and the GABA synthesis inhibitor 3-mercaptopropionic acid. Rats were then anesthetized with isoflurane, and induction time was quantified as loss of righting reflex. Breathing rate was also measured. Relative to wakefulness, GABA levels were significantly decreased by isoflurane. Increased power in the electroencephalogram and decreased activity in the electromyogram caused by isoflurane covaried with pontine reticular formation GABA levels. Nipecotic acid and 3-mercaptopropionic acid significantly increased and decreased, respectively, isoflurane induction time. Nipecotic acid also increased breathing rate. Decreasing pontine reticular formation GABA levels comprises one mechanism by which isoflurane causes loss of consciousness, altered cortical excitability, muscular hypotonia, and decreased respiratory rate.

Induction, adaptation and recovery of biological responses: implications for environmental monitoring.

PubMed

Wu, Rudolf S S; Siu, William H L; Shin, Paul K S

2005-01-01

A wide range of biological responses have been used to identify exposure to contaminants, monitor spatial and temporal changes in contamination levels, provide early warning of environmental deterioration and indicate occurrences of adverse ecological consequences. To be useful in environmental monitoring, a biological response must reflect the environmental stress over time in a quantitative way. We here argue that the time required for initial induction, maximum induction, adaptation and recovery of these stress responses must first be fully understood and considered before they can be used in environmental monitoring, or else erroneous conclusions (both false-negative and false-positive) may be drawn when interpreting results. In this study, data on initial induction, maximum induction, adaptation and recovery of stress responses at various biological hierarchies (i.e., molecular, biochemical, physiological, behavioral, cytological, population and community responses) upon exposure to environmentally relevant levels of contaminants (i.e., metals, oil, polycyclic aromatic hydrocarbons (PAHs), organochlorines, organophosphates, endocrine disruptors) were extracted from 922 papers in the biomarker literature and analyzed. Statistical analyses showed that: (a) many stress responses may decline with time after induction (i.e., adaptation), even if the level of stress remains constant; (b) times for maximum induction and recovery of biochemical responses are positively related; (c) there is no evidence to support the general belief that time for induction of responses at a lower biological hierarchy (i.e., molecular responses and biochemical responses) is shorter than that at higher hierarchy (i.e., physiological, cytological and behavioral responses), although longer recovery time is found for population and community responses; (d) there are significant differences in times required for induction and adaptation of biological responses caused by different types of contaminants; (e) times required for initial and maximum induction of physiological responses in fish are significantly longer than those in crustaceans; and (f) there is a paucity of data on adaptation and recovery of responses, especially those at population and community levels. The above analyses highlight: (1) the limitations and possible erroneous conclusions in the present use of biomarkers in biomonitoring programs, (2) the importance of understanding the details of temporal changes of biological responses before employing them in environmental management, and (3) the suitability of using specific animal groups as bioindicator species.

Induction of hsp70, hsp60, hsp83 and hsp26 and oxidative stress markers in benzene, toluene and xylene exposed Drosophila melanogaster: Role of ROS generation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Mahendra Pratap; Reddy, M.M. Krishna.; Mathur, N.

2009-03-01

Exposure to benzene, toluene and xylene in the human population may pose a health risk. We tested a working hypothesis that these test chemicals cause cellular toxicity to a non-target organism, Drosophila melanogaster. Third instar larvae of D. melanogaster transgenic for hsp70, hsp83 and hsp26 and Oregon R{sup +} strain were exposed to 1.0-100.0 mM benzene, toluene and xylene for 2-48 h to examine the heat shock proteins (hsps), ROS generation, anti-oxidant stress markers and developmental end points. The test chemicals elicited a concentration- and time-dependent significant (p < 0.01) induction of the hsps in the exposed organism in themore » order of hsp70 > hsp83 {>=} hsp26 as evident by {beta}-galactosidase activity after 24 h. RT-PCR amplification studies in Oregon R{sup +} larvae revealed a similar induction pattern of these genes along with hsp60 in the order of hsp70 > hsp60 > hsp26 {>=} hsp83. Under similar experimental conditions, a significant induction of ROS generation and oxidative stress markers viz. superoxide dismutase, catalase, glutathione S-transferase, thioredoxin reductase, glutathione, malondialdehyde and protein carbonyl content was observed. Sub-organismal response was propagated towards organismal response i.e., a delay in the emergence of flies and their reproductive performance. While hsp70 was predominantly induced in the organism till 24 h of treatment with the test chemicals, a significant or insignificant regression of Hsp70 after 48 h was concurrent with a significant induction (p < 0.01) of hsp60 > hsp83 {>=} hsp26 in comparison to the former. A significant positive correlation was observed between ROS generation and these hsps in the exposed organism till 24 h and a negative correlation between ROS generation and hsp70 in them after 48 h indicating a modulatory role of ROS in the induction of hsps. The study suggests that among the tested hsps, hsp70 may be used as an early bioindicator of cellular toxicity against benzene, toluene and xylene and D. melanogaster as an alternative animal model for screening the risk posed by environmental chemicals.« less

Cardiovascular and behavioral responses of gray wolves to ketamine-xylazine immobilization and antagonism by yohimbine

USGS Publications Warehouse

Kreeger, T.J.; Faggella, A.M.; Seal, U.S.; Mech, L.D.; Callahan, Margaret; Hall, B.

1987-01-01

Adult wolves (Canis lupus) were immobilized with 6.6 mg/kg ketamine hydrochloride (KET) and 2.2 mg/kg xylazine hydrochloride (XYL) administered intramuscularly. Induction time was 4.6 ± 0.3 min (x̄ ± SE). Immobilization resulted in significant bradycardia and hypertension (P < 0.05). Twenty min after induction, the wolves were given 0.05–0.60 mg/kg yohimbine hydrochloride (YOH). Yohimbine given intravenously produced dose-related increases in heart rate (HR) with doses >0.15 mg/kg resulting in extreme tachycardia (>300 bpm). All doses of YOH caused a temporary decrease in mean arterial blood pressure (MABP) with some individual animals manifesting profound hypotension (<30 torr) at doses >0.15 mg/kg. Increasing the dose of YOH above 0.15 mg/kg did not significantly decrease either arousal or ambulation times. Administering YOH at 40 or 60 min after induction resulted in decreased arousal and ambulation times. Stimulation by weighing and taking repeated blood samples during anesthesia did not shorten arousal times. We recommend that wolves immobilized with XYL-KET be antagonized with doses of YOH <0.15 mg/kg.

Cognitive Skill and Traditional Trance Hypnotic Inductions: A Within-Subjects Comparison.

ERIC Educational Resources Information Center

Vickery, Anne R.; And Others

1985-01-01

Compared a traditional trance hypnotic induction and a cognitive skill induction using a within-subjects design with college students (N=40). The skill induction enhanced responses to suggestions and produced marginally significant increments in behavioral responses when preceded by the trance induction, but there were no significant differences…

The sensory thalamus and cerebral motor cortex are affected concurrently during induction of anesthesia with propofol: a case series with intracranial electroencephalogram recordings.

PubMed

Verdonck, Olivier; Reed, Sean J; Hall, Jeffery; Gotman, Jean; Plourde, Gilles

2014-03-01

Brain imaging studies suggest that loss of consciousness induced by general anesthetics is associated with impairment of thalamic function. There is, however, limited information on the time course of these changes. We recently obtained intracranial electroencephalogram (EEG) recordings from the ventroposterolateral (VPL) nucleus of the thalamus and from the motor cortex during induction of anesthesia in three patients to study the time course of the alterations of cortical and thalamic function. The patients were American Society of Anesthesiologists physical status I-II males aged 33-57 yr with intractable central pain caused by brachial plexus injury (patient 1 and 2) or insular infarct (patient 3). Anesthesia was induced with propofol (2.5-3.1 mg·kg(-1) over 30-45 sec) followed, after loss of consciousness, by rocuronium for tracheal intubation. The data retained for analysis are from one minute before the start of propofol to 110 sec later during ventilation of the patients' lungs before tracheal intubation. Spectral analysis was used to measure absolute EEG power. Propofol caused significant increases of cortical and thalamic power in the delta to beta frequency bands (1-30 Hz). These increases of cortical and thalamic power occurred either concomitantly or within seconds of each other. Propofol also caused a decrease in cortical and thalamic high-gamma (62-200 Hz) power that also followed a similar time course. We conclude that induction of anesthesia with propofol in these patients was associated with concurrent alterations of cortical and sensory thalamic activity.

Modulation of porcine biotransformation enzymes by anthelmintic therapy with fenbendazole and flubendazole.

PubMed

Savlík, M; Fimanová, K; Szotáková, B; Lamka, J; Skálová, L

2006-06-01

Fenbendazole (FEN) and flubendazole (FLU) are benzimidazole anthelmintics often used in pig management for the control of nematodoses. The in vivo study presented here was designed to test the influence of FLU and FEN on cytochrome P4501A and other cytochrome P450 (CYP) isoforms, UDP-glucuronosyl transferase and several carbonyl reducing enzymes. The results indicated that FEN (in a single therapeutic dose as well as in repeated therapeutic doses) caused significant induction of pig CYP1A, while FLU did not show an inductive effect towards this isoform. Some of the other hepatic and intestinal biotransformation enzymes that were assayed were moderately influenced by FEN or FLU. Strong CYP1A induction following FEN therapy in pigs may negatively affect the efficacy and pharmacokinetics of FEN itself or other simultaneously or consecutively administered drugs. From the perspective of biotransformation enzyme modulation, FLU would appear to be a more convenient anthelmintic therapy of pigs than FEN.

Effects of previous ovarian surgery on the follicular response to ovulation induction in an in vitro fertilization program.

PubMed

Hornstein, M D; Barbieri, R L; McShane, P M

1989-04-01

This study examined the effects of previous ovarian surgery on the clinical response to ovulation induction with clomiphene citrate-human menopausal gonadotropin in an in vitro fertilization program. Patients were divided into five clinical groups: group A (n = 63), no previous ovarian surgery; B (n = 9), unilateral cystectomy; C (n = 6), unilateral oophorectomy with no contralateral ovarian surgery; D (n = 7), bilateral ovarian surgery with both ovaries present; and E (n = 4), unilateral oophorectomy and contralateral cystectomy. Patients in group E demonstrated significantly lower serum estradiol on cycle days 9-11 (P less than or equal to .05) and fewer follicles on cycle days 11-12 (P less than or equal to .05) than did patients in groups A-D. The percentage of cancelled cycles increased with increasing amounts of ovarian surgery (P less than or equal to .03). The study suggests that one cause of a poor response to ovulation induction for in vitro fertilization may be prior extensive ovarian surgery.

Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis.

PubMed

Lim, Chae Jin; Lee, Yong-Moon; Kang, Seung Goo; Lim, Hyung W; Shin, Kyong-Oh; Jeong, Se Kyoo; Huh, Yang Hoon; Choi, Suin; Kor, Myungho; Seo, Ho Seong; Park, Byeong Deog; Park, Keedon; Ahn, Jeong Keun; Uchida, Yoshikazu; Park, Kyungho

2017-09-01

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by SA-β-gal staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.

Principle and Performance of Gas Self-inducing Reactors and Applications to Biotechnology.

PubMed

Ye, Qin; Li, Zhimin; Wu, Hui

2016-01-01

Gas-liquid contacting is an important unit operation in chemical and biochemical processes, but the gas utilization efficiency is low in conventional gas-liquid contactors especially for sparingly soluble gases. The gas self-inducing impeller is able to recycle gas in the headspace of a reactor to the liquid without utilization of additional equipment such as a gas compressor, and thus, the gas utilization efficiency is significantly enhanced. Gas induction is caused by the low pressure or deep vortex at a sufficiently high impeller speed, and the speed at which gas induction starts is termed the critical speed. The critical impeller speed, gas-induction flow rate, power consumption, and gas-liquid mass transfer are determined by the impeller design and operation conditions. When the reactor is operated in a dead-end mode, all the introduced gas can be completely used, and this feature is especially favorable to flammable and/or toxic gases. In this article, the principles, designs, characteristics of self-inducing reactors, and applications to biotechnology are described.

Differential Involvement of β-Glucosidases from Hypocrea jecorina in Rapid Induction of Cellulase Genes by Cellulose and Cellobiose

PubMed Central

Zhou, Qingxin; Xu, Jintao; Kou, Yanbo; Lv, Xinxing; Zhang, Xi; Zhao, Guolei; Zhang, Weixin; Chen, Guanjun

2012-01-01

Appropriate perception of cellulose outside the cell by transforming it into an intracellular signal ensures the rapid production of cellulases by cellulolytic Hypocrea jecorina. The major extracellular β-glucosidase BglI (CEL3a) has been shown to contribute to the efficient induction of cellulase genes. Multiple β-glucosidases belonging to glycosyl hydrolase (GH) family 3 and 1, however, exist in H. jecorina. Here we demonstrated that CEL1b, like CEL1a, was an intracellular β-glucosidase displaying in vitro transglycosylation activity. We then found evidence that these two major intracellular β-glucosidases were involved in the rapid induction of cellulase genes by insoluble cellulose. Deletion of cel1a and cel1b significantly compromised the efficient gene expression of the major cellulase gene, cbh1. Simultaneous absence of BglI, CEL1a, and CEL1b caused the induction of the cellulase gene by cellulose to further deteriorate. The induction defect, however, was not observed with cellobiose. The absence of the three β-glucosidases, rather, facilitated the induced synthesis of cellulase on cellobiose. Furthermore, addition of cellobiose restored the productive induction on cellulose in the deletion strains. The results indicate that the three β-glucosidases may not participate in transforming cellobiose beyond hydrolysis to provoke cellulase formation in H. jecorina. They may otherwise contribute to the accumulation of cellobiose from cellulose as inducing signals. PMID:23002106

Early induction of c-Myc is associated with neuronal cell death.

PubMed

Lee, Hyun-Pil; Kudo, Wataru; Zhu, Xiongwei; Smith, Mark A; Lee, Hyoung-gon

2011-11-14

Neuronal cell cycle activation has been implicated in neurodegenerative diseases such as Alzheimer's disease, while the initiating mechanism of cell cycle activation remains to be determined. Interestingly, our previous studies have shown that cell cycle activation by c-Myc (Myc) leads to neuronal cell death which suggests Myc might be a key regulator of cell cycle re-entry mediated neuronal cell death. However, the pattern of Myc expression in the process of neuronal cell death has not been addressed. To this end, we examined Myc induction by the neurotoxic agents camptothecin and amyloid-β peptide in a differentiated SH-SY5Y neuronal cell culture model. Myc expression was found to be significantly increased following either treatment and importantly, the induction of Myc preceded neuronal cell death suggesting it is an early event of neuronal cell death. Since ectopic expression of Myc in neurons causes the cell cycle activation and neurodegeneration in vivo, the current data suggest that induction of Myc by neurotoxic agents or other disease factors might be a key mediator in cell cycle activation and consequent cell death that is a feature of neurodegenerative diseases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Cytochrome P4501A induction, benzo[a]pyrene metabolism, and nucleotide adduct formation in fish hepatoma cells: Effect of preexposure to 3,3',4,4',5-pentachlorobiphenyl

USGS Publications Warehouse

Smeets, J.M.W.; Voormolen, A.; Tillitt, D.E.; Everaarts, J.M.; Seinen, W.; Vanden Berg, M.D.

1999-01-01

In PLHC-1 hepatoma cells, benzo[a]pyrene (B[a]P) caused a maximum induction of cytochrome P4501A (CYP1A) activity, measured as ethoxyresorufin O-deethylation (EROD), after 4 to 8 h of exposure, depending on the B[a]P concentration. The decline of EROD activity at longer exposure times was probably caused by the rapid metabolism of B[a]P in this system (57% metabolism within 4 h incubation). In subsequent experiments, PLHC-1 cells were preinduced with PCB 126 for 24 h and then received a dose of 10, 100, or 1,000 nM 3H-B[a]P. A 1-nM concentration of PCB 126 caused an 80-fold induction of CYP1A activity, resulting in an increase in B[a]P metabolism of less than 10%, except at the highest concentration of B[a]P (1,000 nM), where a 50% increase was observed. In another experiment, an 80-fold induction of CYP1A activity caused a 20% increase in the metabolism of B[a]P (100 nM), and RNA adduct formation was increased approximately twofold. These results indicate that, at exposure concentrations up to 100 nM B[a]P, CYP1A activity is not rate limiting for B[a]P metabolism. Furthermore, CYP1A seems to also he specifically involved in B[a]P activation in PLHC-1 cells. However, CYP1A induction causes only a relatively small increase in activation, probably because of the action of other enzymes involved in B[a]P activation and deactivation.

Shock wave trauma leads to inflammatory response and morphological activation in macrophage cell lines, but does not induce iNOS or NO synthesis.

PubMed

Günther, Mattias; Plantman, Stefan; Gahm, Caroline; Sondén, Anders; Risling, Mårten; Mathiesen, Tiit

2014-12-01

Experimental CNS trauma results in post-traumatic inflammation for which microglia and macrophages are vital. Experimental brain contusion entails iNOS synthesis and formation of free radicals, NO and peroxynitrite. Shock wave trauma can be used as a model of high-energy trauma in cell culture. It is known that shock wave trauma causes sub-lytic injury and inflammatory activation in endothelial cells. Mechanical disruption of red blood cells can induce iNOS synthesis in experimental systems. However, it is not known whether trauma can induce activation and iNOS synthesis in inflammatory cell lines with microglial or macrophage lineage. We studied the response and activation in two macrophage cell lines and the consequence for iNOS and NO formation after shock wave trauma. Two macrophage cell lines from rat (NR8383) and mouse (RAW264.7) were exposed to shock wave trauma by the Flyer Plate method. The cellular response was investigated by Affymetrix gene arrays. Cell survival and morphological activation was monitored for 24 h in a Cell-IQ live cell imaging system. iNOS induction and NO synthesis were analyzed by Western blot, in cell Western IR-immunofluorescence, and Griess nitrite assay. Morphological signs of activation were detected in both macrophage cell lines. The activation of RAW264.7 was statistically significant (p < 0.05), but activation of NR8383 did not pass the threshold of statistical significance alpha (p > 0.05). The growth rate of idle cells was unaffected and growth arrest was not seen. Trauma did not result in iNOS synthesis or NO induction. Gene array analyses showed high enrichment for inflammatory response, G-protein coupled signaling, detection of stimulus and chemotaxis. Shock wave trauma combined with low LPS stimulation instead led to high enrichment in apoptosis, IL-8 signaling, mitosis and DNA-related activities. LPS/IFN-ɣ stimulation caused iNOS and NO induction and morphological activation in both cell lines. Shock wave trauma by the Flyer Plate method caused an inflammatory response and morphological signs of activation in two macrophage cell lines, while iNOS induction appeared to require humoral signaling by LPS/IFN-ɣ. Our findings indicated that direct energy transfer by trauma can activate macrophages directly without humoral mediators, which comprises a novel activation mechanism of macrophages.

Inductive tuners for microwave driven discharge lamps

DOEpatents

Simpson, James E.

1999-01-01

An RF powered electrodeless lamp utilizing an inductive tuner in the waveguide which couples the RF power to the lamp cavity, for reducing reflected RF power and causing the lamp to operate efficiently.

Efficacy of a 2-month dietary supplementation with polyunsaturated fatty acids in dry eye induced by scopolamine in a rat model.

PubMed

Viau, Sabrina; Maire, Marie-Annick; Pasquis, Bruno; Grégoire, Stéphane; Acar, Niyazi; Bron, Alain M; Bretillon, Lionel; Creuzot-Garcher, Catherine P; Joffre, Corinne

2009-08-01

This study was conducted to evaluate the efficacy of dietary n-6 and n-3 polyunsaturated fatty acids (PUFAs) in dry eye in a rat model. Female Lewis rats were fed with diets containing (1) gamma-linolenic acid (GLA), (2) eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), or (3) GLA + EPA + DHA, for 2 months before the induction of dry eye using a continuous delivery of scopolamine and during scopolamine treatment. Two, 10 and 28 days after dry-eye induction, clinical signs of corneal dryness were evaluated in vivo using fluorescein staining. MHC II expression and mucin rMuc5AC production in the conjunctival epithelium were evaluated by immunostaining. Lipids and prostaglandins (PGs) E(1) and E(2) were analysed from the exorbital lacrimal gland (LG). Dietary PUFAs minimised the occurrence of corneal keratitis 28 days after induction of dry eye. The decrease in mucin production observed on the conjunctival epithelium was partially prevented by EPA + DHA supplementation after 2 days of scopolamine treatment, as well as by GLA and GLA + EPA + DHA diets after 10 days of treatment. The overexpression of MHC II in the conjunctival epithelium caused by dry eye induction was significantly reduced only with the GLA + EPA + DHA diet after 28 days of treatment. Dietary PUFAs were incorporated into phospholipids of the exorbital LG. Induction of dry eye was associated with a significant increase in PGE(1) and PGE(2) levels in the exorbital LG, which was inhibited by dietary EPA + DHA at 10 days (for PGE(2)) and 28 days (for PGE(1)). Dietary GLA, EPA and DHA significantly interfered with lipid homeostasis in the exorbital LG and partially prevented the course of dry eye. In particular, our results demonstrate the efficacy of the combination of n-6 and n-3 PUFAs.

Contraintes residuelles et leurs impacts sur l'amorcage de fissures en fatigue de flexion dans des engrenages aeronautiques durcis superficiellement par induction

NASA Astrophysics Data System (ADS)

Savaria, Vincent

The optimization of gearing for aeronautical engines depends on the development of surface hardening processes to significantly improve in-service durability. Induction heating followed by quenching is a treatment increasingly used in this field to improve the fatigue resistance of critical components such as gears. In this context, this thesis studies the impact of the induction process parameters on residual stresses and the effects of those stresses on the bending fatigue of induction hardened gears. Two existing residual stress measurement techniques, X-ray diffraction and the contour method, were adapted for induction hardened components. The residual stress measurement by X-ray diffraction technique has been significantly improved in this thesis by the consideration of the variation of the X-ray elastic constant at different locations in the hardened layer and the development of a finite element based layer removal correction method that enabled more accurate in-depth residual stress measurements in all sort of geometries. The contour method is clearly a powerful tool for residual stress mapping at the core of parts but proved to be inaccurate for near-surface measurements in the case of thin hardened layers. These methods were used to show the effects of several parameters (initial hardness, preheating, final heating, tempering) with discs and aeronautical spur gears. The results indicate that two induction treatments can sometimes produce two different residual stress distributions (amplitude, severity of gradient in the transition zone, etc.) for a similar hardened depth. The bending fatigue of those gears was studied experimentally with a single tooth bending test rig and numerically with the proposition of a fatigue model for the calculation of the bending endurance limit. The calibration of the model was based on fatigue tests results on traction and torsion specimens. Bending fatigue testing results on gears confirmed the overall accuracy of the proposed model predictions. The Crossland criterion without the gradient effect gave better predictions when compared with the experimental results for that particular case. This 3D multiaxial fatigue prediction model represents a significant improvement over previous approaches by the simultaneous consideration of the so-called gradient effect, residual stresses, surface roughness and the variation of properties caused by the surface hardening. The induction treatments used in this study improved the bending fatigue resistance of spur gears by 45 to 71 % depending on the case.

[Leading causes of death during the induction therapy in pediatric patients with acute lymphoblastic leukemia].

PubMed

Aguilar-Hernández, Máximo; Fernández-Castillo, Gabriela; Núñez-Villegas, Nora Nancy; Pérez-Casillas, Ruy Xavier; Núñez-Enríquez, Juan Carlos

2017-01-01

Leukemias are the leading cause of childhood cancer. In most developed countries 1-2% of patients die during remission induction; however, in developing countries, this figure is higher and the causes of death apparently vary among the populations studied. The aim was to determine the cause of death during remission induction in pediatric patients with acute lymphoblastic leukemia (ALL) in the hospital "Dr. Gaudencio González Garza" of Centro Médico Nacional La Raza from January 1, 2009, to December 31, 2014. A retrospective cohort study was carried out and a descriptive statistical analysis was performed. During the study period, a total of 463 patients with ALL were diagnosed, out of which 5.4% died (n = 25). Among the patients who died, 64% (n = 16) were female and 60% had high-risk clinical features at diagnosis. The main causes of death were septic shock and bleeding. Early mortality was five times higher than the one reported for developed countries, while the causes of death did not differ. Close monitoring is necessary to detect and promptly treat complications secondary to chemotherapy toxicity in Mexican pediatric patients with ALL.

Morphology and contractile gene expression of adipose-derived mesenchymal stem cells in response to short-term cyclic uniaxial strain and TGF-β1.

PubMed

Rashidi, Neda; Tafazzoli-Shadpour, Mohammad; Haghighipour, Nooshin; Khani, Mohammad-Mehdi

2018-06-27

Previous studies have shown smooth muscle induction in adipose-derived mesenchymal stem cells (ASCs) caused by long-term cyclic stretch. Here we examined the capability of the short-term straining with time steps of 4, 8, 16 and 24 h alone or combined with TGF-β1 on smooth muscle induction of rabbit ASCs. Alterations in cell morphology were quantified through the cell shape index and orientation angle, and expression levels of α-SMA, SM22-α, h-caldesmon and calponin3 markers were examined using the real-time polymerase chain reaction (PCR) method. Moreover, F-actin cytoskeleton organization was observed by fluorescence staining. Mechanical strain either alone or combined with growth factor treatment caused significant up-regulation of both early and intermediate smooth muscle cells (SMCs) specific markers during the initial hours of stimulation peaking in 8 to 16 h. Furthermore, gradual alignment of cells perpendicular to the strain direction during loading time, and cell elongation resembling contractile SMC phenotype, together with alignment and reorganization of F-actin fibers were observed. Considering previously reported protein up-regulation in following days of straining, the effects of short-term cyclic stretch on smooth muscle induction of ASCs were revealed which can be helpful in achieving functional contractile SMCs through synergistic mechano-chemical regulation of ASCs as an appealing cell source for vascular tissue engineering.

Zinc supplementation augments TGF-β1-dependent regulatory T cell induction.

PubMed

Maywald, Martina; Meurer, Steffen K; Weiskirchen, Ralf; Rink, Lothar

2017-03-01

Regulatory T cells (Treg) play a pivotal role in immune regulation. For proper immune function, also trace elements such as zinc, and anti-inflammatory cytokines, including transforming growth factor beta 1 (TGF-β1) and interleukin (IL)-10 are indispensable. Hence, in this study the influence of TGF-β1, IL-10, and zinc supplementation on Treg cells differentiation was investigated. A synergistic effect of a combined zinc and TGF-β1 treatment on Foxp3 expression in peripheral blood mononuclear cells and mixed lymphocyte cultures (MLC) was found by performing Western blot analysis. Additionally, combined treatment causes elevated Smad 2/3 phosphorylation, which plays an important role in Foxp3 expression. This is due to a TGF-β1-mediated increase of intracellular-free zinc measured by zinc probes Fluozin3-AM and ZinPyr-1. Moreover, zinc as well as TGF-β1 treatment caused significantly reduced interferon (IFN)-γ secretion in MLC. Combined zinc and TGF-β1 treatment provoked an increased Treg cell induction due to a triggered intracellular zinc signal, which in association with an increased Smad 2/3 activation leads to a boosted Foxp3 expression and resulting in an ameliorated allogeneic reaction in MLC. Thus, zinc can be used as a favorable additive to elevate the induction of Treg cells in adverse immune reactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The protective effect of rapid cold-hardening develops more quickly in frozen versus supercooled larvae of the Antarctic midge, Belgica antarctica.

PubMed

Kawarasaki, Yuta; Teets, Nicholas M; Denlinger, David L; Lee, Richard E

2013-10-15

During the austral summer, larvae of the terrestrial midge Belgica antarctica (Diptera: Chironomidae) experience highly variable and often unpredictable thermal conditions. In addition to remaining freeze tolerant year-round, larvae are capable of swiftly increasing their cold tolerance through the rapid cold-hardening (RCH) response. The present study compared the induction of RCH in frozen versus supercooled larvae. At the same induction temperature, RCH occurred more rapidly and conferred a greater level of cryoprotection in frozen versus supercooled larvae. Furthermore, RCH in frozen larvae could be induced at temperatures as low as -12°C, which is the lowest temperature reported to induce RCH. Remarkably, as little as 15 min at -5°C significantly enhanced larval cold tolerance. Not only is protection from RCH acquired swiftly, but it is also quickly lost after thawing for 2 h at 2°C. Because the primary difference between frozen and supercooled larvae is cellular dehydration caused by freeze concentration of body fluids, we also compared the effects of acclimation in dehydrated versus frozen larvae. Because slow dehydration without chilling significantly increased larval survival to a subsequent cold exposure, we hypothesize that cellular dehydration caused by freeze concentration promotes the rapid acquisition of cold tolerance in frozen larvae.

Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital.

PubMed

Hariparsad, Niresh; Nallani, Srikanth C; Sane, Rucha S; Buckley, Donna J; Buckley, Arthur R; Desai, Pankaj B

2004-11-01

The antiretroviral agent efavirenz enhances the systemic clearance of coadministered drugs that are cytochrome P450 (CYP) 3A4 substrates. The mechanism of the apparent increase in CYP3A4 activity by efavirenz and the magnitude of change relative to other known inducers are not known. The authors tested the hypothesis that increased enzymatic activity by efavirenz entails CYP3A4 induction and activation of the human pregnane X receptor (hPXR), a key transcriptional regulator of CYP3A4. Employing primary cultures of human hepatocytes, they compared the CYP3A4 inductive effects of efavirenz (1-10 microM) to rifampin (10 microM) and phenobarbital (2 mM). A cell-based reporter assay was employed to assess hPXR activation. The authors observed that efavirenz caused a concentration-dependent CYP3A4 induction and hPXR activation. Based on the CYP3A4 activity assay, the average magnitude of induction by efavirenz (5-10 microM) was approximately 3- to 4-fold. In comparison, phenobarbital (2 mM) and rifampin (10 microM) caused a 5- and 6-fold induction, respectively.

Organotin compounds cause structure-dependent induction of progesterone in human choriocarcinoma Jar cells.

PubMed

Hiromori, Youhei; Yui, Hiroki; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Nakanishi, Tsuyoshi

2016-01-01

Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), are typical environmental contaminants and suspected endocrine-disrupting chemicals because they cause masculinization in female mollusks. In addition, previous studies have suggested that the endocrine disruption by organotin compounds leads to activation of peroxisome proliferator-activated receptor (PPAR)γ and retinoid X receptor (RXR). However, whether organotin compounds cause crucial toxicities in human development and reproduction is unclear. We here investigated the structure-dependent effect of 12 tin compounds on mRNA transcription of 3β-hydroxysteroid dehydrogenase type I (3β-HSD I) and progesterone production in human choriocarcinoma Jar cells. TBT, TPT, dibutyltin, monophenyltin, tripropyltin, and tricyclohexyltin enhanced progesterone production in a dose-dependent fashion. Although tetraalkyltin compounds such as tetrabutyltin increased progesterone production, the concentrations necessary for activation were 30-100 times greater than those for trialkyltins. All tested active organotins increased 3β-HSD I mRNA transcription. We further investigated the correlation between the agonistic activity of organotin compounds on PPARγ and their ability to promote progesterone production. Except for DBTCl2, the active organotins significantly induced the transactivation function of PPARγ. In addition, PPARγ knockdown significantly suppressed the induction of mRNA transcription of 3β-HSD I by all active organotins except DBTCl2. These results suggest that some organotin compounds promote progesterone biosynthesis in vitro by inducing 3β-HSD I mRNA transcription via the PPARγ signaling pathway. The placenta represents a potential target organ for these compounds, whose endocrine-disrupting effects might cause local changes in progesterone concentration in pregnant women. Copyright © 2014 Elsevier Ltd. All rights reserved.

Time course of anger and other emotions in women with borderline personality disorder: a preliminary study.

PubMed

Jacob, Gitta A; Guenzler, Cindy; Zimmermann, Sabine; Scheel, Corinna N; Rüsch, Nicolas; Leonhart, Rainer; Nerb, Josef; Lieb, Klaus

2008-09-01

Borderline personality disorder (BPD) is characterized by emotional dysregulation including strong emotional reactions to emotional stimuli and a slow return to baseline emotions. Difficulties controlling anger are particularly prominent in BPD. To experimentally test emotional dysregulation with a special focus on anger, we investigated whether a standardized anger induction by a short story caused stronger and prolonged anger reactions in women with BPD (n=27) as compared to female healthy controls (n=26) and whether other emotions were affected by the anger induction. Although the anger reaction was not stronger in the BPD group, it was significantly prolonged. The BPD group showed also stronger negative emotions over the whole experiment. The study is the first to demonstrate prolonged anger reactions in BPD patients in an experimental setting.

NSrp70 is significant for embryonic growth and development, being a crucial factor for gastrulation and mesoderm induction.

PubMed

Lee, Soo-Ho; Kim, Chowon; Lee, Hyun-Kyung; Kim, Yoo-Kyung; Ismail, Tayaba; Jeong, Youngeun; Park, Kyungyeon; Park, Mae-Ja; Park, Do-Sim; Lee, Hyun-Shik

2016-10-14

NSrp70 (nuclear speckle-related protein 70), a recently discovered protein and it belongs to the serine/arginine (SR) rich related protein family. NSrp70 is recognized as an important splicing factor comprising RNA recognition motif (RRM) and arginine/serine (RS)-like regions at the N- and C-terminus respectively, along with two coiled coil domains at each terminus. However, other functions of NSrp70 remain unelucidated. In this study, we investigated the role of NSrp70 in Xenopus embryogenesis and found that its maternal expression plays a critical role in embryonic development. Knockdown of NSrp70 resulted in dramatic reduction in the length of developing tadpoles and mild to severe malformation in Xenopus embryos. In addition, knockdown of NSrp70 resulted in an extremely short axis by blocking gastrulation and convergent extension. Further, animal cap assays along with activin A treatment revealed that NSrp70 is an essential factor for dorsal mesoderm induction as knockdown of NSrp70 caused a dramatic down-regulation of dorsal mesoderm specific genes and its loss significantly shortened the elongation region of animal caps. In conclusion, NSrp70 is crucial for early embryonic development, influencing gastrulation and mesoderm induction. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuroimmune Function and the Consequences of Alcohol Exposure

PubMed Central

Crews, Fulton T.; Sarkar, Dipak K.; Qin, Liya; Zou, Jian; Boyadjieva, Nadka; Vetreno, Ryan P.

2015-01-01

Induction of neuroimmune genes by binge drinking increases neuronal excitability and oxidative stress, contributing to the neurobiology of alcohol dependence and causing neurodegeneration. Ethanol exposure activates signaling pathways featuring high-mobility group box 1 and Toll-like receptor 4 (TLR4), resulting in induction of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells, which regulates expression of several cytokine genes involved in innate immunity, and its target genes. This leads to persistent neuroimmune responses to ethanol that stimulate TLRs and/or certain glutamate receptors (i.e., N-methyl-d-aspartate receptors). Alcohol also alters stress responses, causing elevation of peripheral cytokines, which further sensitize neuroimmune responses to ethanol. Neuroimmune signaling and glutamate excitotoxicity are linked to alcoholic neurodegeneration. Models of alcohol abuse have identified significant frontal cortical degeneration and loss of hippocampal neurogenesis, consistent with neuroimmune activation pathology contributing to these alcohol-induced, long-lasting changes in the brain. These alcohol-induced long-lasting increases in brain neuroimmune-gene expression also may contribute to the neurobiology of alcohol use disorder. PMID:26695754

Inductive Interference in Rapid Transit Signaling Systems. Volume 1. Theory and Background.

DOT National Transportation Integrated Search

1986-05-01

This report describes the mechanism of inductive interference to audio frequency (AF) signaling systems used in rail transit operations, caused by rail transit vehicles with chopper propulsion control. Choppers are switching circuits composed of high...

Induction signals from Callisto's ionosphere and their implications on a possible subsurface ocean

NASA Astrophysics Data System (ADS)

Hartkorn, Oliver; Saur, Joachim

2017-11-01

We investigate whether induction within Callisto's electrically conductive ionosphere can explain observed magnetic fields which have previously been interpreted as evidence of induction in a saline, electrically conductive subsurface ocean. Callisto's ionosphere is subject to the flow of time-periodic magnetized plasma of Jupiter's magnetosphere, which induces electric fields and electric currents in Callisto's electrically conductive ionosphere. We develop a simple analytic model for a first quantitative understanding of the effects of induction in Callisto's ionosphere caused by the interaction with a time-variable magnetic field environment. With this model, we also investigate how the associated ionospheric currents close in the ambient magnetospheric plasma. Based on our model, we find that the anisotropic nature of Callisto's ionospheric conductivity generates an enhancement effect on ionospheric loop currents which are driven by the time-variable magnetic field. This effect is similar to the Cowling channel effect known from Earth's ionosphere. Subsequently, we numerically calculate the expected induced magnetic fields due to Jupiter's time-variable magnetic field in an anisotropic conductive ionosphere and compare our results with the Galileo C-3 and C-9 flybys. We find that induction within Callisto's ionosphere is responsible for a significant part of the observed magnetic fields. Ionospheric induction creates induced magnetic fields to some extent similar as expected from a subsurface water ocean. Depending on currently unknown properties such as Callisto's nightside ionosphere, the existence of layers of "dirty ice" and the details of the plasma interaction, a water ocean might be located much deeper than previously thought or might not exist at all.

Abscisic Acid accumulates at positive turgor potential in excised soybean seedling growing zones.

PubMed

Creelman, R A; Mullet, J E

1991-04-01

Abscisic acid (ABA) accumulated in soybean (Glycine max [L.] Merr. cv Williams) hypocotyl elongating regions when seedlings were transferred to low water potential vermiculite (Psi = -0.3 megapascals) even though positive turgor is retained in this tissue. Accumulation of ABA in growing zones could occur from de novo biosynthesis within this tissue or transport from adjacent nongrowing zones. Both growing and nongrowing hypocotyl and root tissues accumulated significant levels of ABA when excised and dehydrated to reduce turgor. Surprisingly, excised growing zones (which experienced no water loss) also accumulated ABA when incubated in darkness for 4 hours at 100% relative humidity and 29 degrees C. Induction of ABA accumulation in the excised elongating region of the hypocotyl was not caused by disruption of root pressure or wounding. While excision of hypocotyl elongating regions induced ABA accumulation, no change in either extensin or p33 mRNA levels was observed. Accumulation of extensin or p33 mRNA required more severe wounding. This suggests that ABA is not involved in the response of these genes in wounded tissue and that wound signals are not causing ABA accumulation in excised tissue. Accumulation of ABA in excised elongating regions was correlated with growth inhibition and a decline in turgor to the yield threshold (Psi;(p) = 0.37 megapascals; R Matyssek, S Maruyama, JS Boyer [1988] Plant Physiol 86: 1163-1167). Inhibiting hypocotyl growth by transferring seedlings to lower temperatures or light did not cause ABA accumulation. We conclude that induction of ABA accumulation in growing zones is more sensitive to changes in turgor than the induction which occurs in mature tissues.

Abscisic Acid Accumulates at Positive Turgor Potential in Excised Soybean Seedling Growing Zones 1

PubMed Central

Creelman, Robert A.; Mullet, John E.

1991-01-01

Abscisic acid (ABA) accumulated in soybean (Glycine max [L.] Merr. cv Williams) hypocotyl elongating regions when seedlings were transferred to low water potential vermiculite (Ψ = −0.3 megapascals) even though positive turgor is retained in this tissue. Accumulation of ABA in growing zones could occur from de novo biosynthesis within this tissue or transport from adjacent nongrowing zones. Both growing and nongrowing hypocotyl and root tissues accumulated significant levels of ABA when excised and dehydrated to reduce turgor. Surprisingly, excised growing zones (which experienced no water loss) also accumulated ABA when incubated in darkness for 4 hours at 100% relative humidity and 29°C. Induction of ABA accumulation in the excised elongating region of the hypocotyl was not caused by disruption of root pressure or wounding. While excision of hypocotyl elongating regions induced ABA accumulation, no change in either extensin or p33 mRNA levels was observed. Accumulation of extensin or p33 mRNA required more severe wounding. This suggests that ABA is not involved in the response of these genes in wounded tissue and that wound signals are not causing ABA accumulation in excised tissue. Accumulation of ABA in excised elongating regions was correlated with growth inhibition and a decline in turgor to the yield threshold (Ψ;p = 0.37 megapascals; R Matyssek, S Maruyama, JS Boyer [1988] Plant Physiol 86: 1163-1167). Inhibiting hypocotyl growth by transferring seedlings to lower temperatures or light did not cause ABA accumulation. We conclude that induction of ABA accumulation in growing zones is more sensitive to changes in turgor than the induction which occurs in mature tissues. Images Figure 2 PMID:16668113

Functional Dependence for Calculation of Additional Real-Power Losses in a Double-Wound Supply Transformer Caused by Unbalanced Active Inductive Load in a Star Connection with an Insulated Neutral

ERIC Educational Resources Information Center

Kostinskiy, Sergey S.; Troitskiy, Anatoly I.

2016-01-01

This article deals with the problem of calculating the additional real-power losses in double-wound supply transformers with voltage class 6 (10)/0,4 kV, caused by unbalanced active inductive load connected in a star connection with an insulated neutral. When solving the problem, authors used the theory of electric circuits, method of balanced…

Plants respond to leaf vibrations caused by insect herbivore chewing.

PubMed

Appel, H M; Cocroft, R B

2014-08-01

Plant germination and growth can be influenced by sound, but the ecological significance of these responses is unclear. We asked whether acoustic energy generated by the feeding of insect herbivores was detected by plants. We report that the vibrations caused by insect feeding can elicit chemical defenses. Arabidopsis thaliana (L.) rosettes pre-treated with the vibrations caused by caterpillar feeding had higher levels of glucosinolate and anthocyanin defenses when subsequently fed upon by Pieris rapae (L.) caterpillars than did untreated plants. The plants also discriminated between the vibrations caused by chewing and those caused by wind or insect song. Plants thus respond to herbivore-generated vibrations in a selective and ecologically meaningful way. A vibration signaling pathway would complement the known signaling pathways that rely on volatile, electrical, or phloem-borne signals. We suggest that vibration may represent a new long distance signaling mechanism in plant-insect interactions that contributes to systemic induction of chemical defenses.

Respiratory infection with Francisella novicida induces rapid dystrophic cardiac calcinosis (DCC).

PubMed

Roth, Kimberly M; Oghumu, Steve; Satoskar, Anjali A; Gunn, John S; van Rooijen, Nico; Satoskar, Abhay R

2008-06-01

Francisella tularensis causes pulmonary tularemia and death in humans when left untreated. Here, using a novel aerosol infection model, we show that acute pulmonary Francisella novicida infection not only causes pneumonia and liver damage, but also induces dystrophic cardiac calcinosis (DCC) in BALB/c mice. C57BL/6 mice also develop pneumonia and hepatic damage, but fail to develop DCC. Development of DCC in BALB/c mice is associated with significant induction of RANKL but not osteopontin in their organs. Depletion of lung macrophages prior to infection markedly reduces pericarditis and calcification in BALB/c mice but does not increase their susceptibility to infection.

Induction of Inducible Nitric Oxide Synthase by Lipopolysaccharide and the Influences of Cell Volume Changes, Stress Hormones and Oxidative Stress on Nitric Oxide Efflux from the Perfused Liver of Air-Breathing Catfish, Heteropneustes fossilis

PubMed Central

Choudhury, Mahua G.; Saha, Nirmalendu

2016-01-01

The air-breathing singhi catfish (Heteropneustes fossilis) is frequently being challenged by bacterial contaminants, and different environmental insults like osmotic, hyper-ammonia, dehydration and oxidative stresses in its natural habitats throughout the year. The main objectives of the present investigation were to determine (a) the possible induction of inducible nitric oxide synthase (iNOS) gene with enhanced production of nitric oxide (NO) by intra-peritoneal injection of lipopolysaccharide (LPS) (a bacterial endotoxin), and (b) to determine the effects of hepatic cell volume changes due to anisotonicity or by infusion of certain metabolites, stress hormones and by induction of oxidative stress on production of NO from the iNOS-induced perfused liver of singhi catfish. Intra-peritoneal injection of LPS led to induction of iNOS gene and localized tissue specific expression of iNOS enzyme with more production and accumulation of NO in different tissues of singhi catfish. Further, changes of hydration status/cell volume, caused either by anisotonicity or by infusion of certain metabolites such as glutamine plus glycine and adenosine, affected the NO production from the perfused liver of iNOS-induced singhi catfish. In general, increase of hydration status/cell swelling due to hypotonicity caused decrease, and decrease of hydration status/cell shrinkage due to hypertonicity caused increase of NO efflux from the perfused liver, thus suggesting that changes in hydration status/cell volume of hepatic cells serve as a potent modulator for regulating the NO production. Significant increase of NO efflux from the perfused liver was also observed while infusing the liver with stress hormones like epinephrine and norepinephrine, accompanied with decrease of hydration status/cell volume of hepatic cells. Further, oxidative stress, caused due to infusion of t-butyl hydroperoxide and hydrogen peroxide separately, in the perfused liver of singhi catfish, resulted in significant increase of NO efflux accompanied with decrease of hydration status/cell volume of hepatic cells. However, the reasons for these cell volume-sensitive changes of NO efflux from the liver of singhi catfish are not fully understood with the available data. Nonetheless, enhanced or decreased production of NO from the perfused liver under osmotic stress, in presence of stress hormones and oxidative stress reflected its potential role in cellular homeostasis and also for better adaptations under environmental challenges. This is the first report of osmosensitive and oxidative stress-induced changes of NO production and efflux from the liver of any teleosts. Further, the level of expression of iNOS in this singhi catfish could also serve as an important indicator to determine the pathological status of the external environment. PMID:26950213

Induction of Inducible Nitric Oxide Synthase by Lipopolysaccharide and the Influences of Cell Volume Changes, Stress Hormones and Oxidative Stress on Nitric Oxide Efflux from the Perfused Liver of Air-Breathing Catfish, Heteropneustes fossilis.

PubMed

Choudhury, Mahua G; Saha, Nirmalendu

2016-01-01

The air-breathing singhi catfish (Heteropneustes fossilis) is frequently being challenged by bacterial contaminants, and different environmental insults like osmotic, hyper-ammonia, dehydration and oxidative stresses in its natural habitats throughout the year. The main objectives of the present investigation were to determine (a) the possible induction of inducible nitric oxide synthase (iNOS) gene with enhanced production of nitric oxide (NO) by intra-peritoneal injection of lipopolysaccharide (LPS) (a bacterial endotoxin), and (b) to determine the effects of hepatic cell volume changes due to anisotonicity or by infusion of certain metabolites, stress hormones and by induction of oxidative stress on production of NO from the iNOS-induced perfused liver of singhi catfish. Intra-peritoneal injection of LPS led to induction of iNOS gene and localized tissue specific expression of iNOS enzyme with more production and accumulation of NO in different tissues of singhi catfish. Further, changes of hydration status/cell volume, caused either by anisotonicity or by infusion of certain metabolites such as glutamine plus glycine and adenosine, affected the NO production from the perfused liver of iNOS-induced singhi catfish. In general, increase of hydration status/cell swelling due to hypotonicity caused decrease, and decrease of hydration status/cell shrinkage due to hypertonicity caused increase of NO efflux from the perfused liver, thus suggesting that changes in hydration status/cell volume of hepatic cells serve as a potent modulator for regulating the NO production. Significant increase of NO efflux from the perfused liver was also observed while infusing the liver with stress hormones like epinephrine and norepinephrine, accompanied with decrease of hydration status/cell volume of hepatic cells. Further, oxidative stress, caused due to infusion of t-butyl hydroperoxide and hydrogen peroxide separately, in the perfused liver of singhi catfish, resulted in significant increase of NO efflux accompanied with decrease of hydration status/cell volume of hepatic cells. However, the reasons for these cell volume-sensitive changes of NO efflux from the liver of singhi catfish are not fully understood with the available data. Nonetheless, enhanced or decreased production of NO from the perfused liver under osmotic stress, in presence of stress hormones and oxidative stress reflected its potential role in cellular homeostasis and also for better adaptations under environmental challenges. This is the first report of osmosensitive and oxidative stress-induced changes of NO production and efflux from the liver of any teleosts. Further, the level of expression of iNOS in this singhi catfish could also serve as an important indicator to determine the pathological status of the external environment.

Coal dust alters β-naphthoflavone-induced aryl hydrocarbon receptor nuclear translocation in alveolar type II cells

PubMed Central

Ghanem, Mohamed M; Battelli, Lori A; Law, Brandon F; Castranova, Vincent; Kashon, Michael L; Nath, Joginder; Hubbs, Ann F

2009-01-01

Background Many polycyclic aromatic hydrocarbons (PAHs) can cause DNA adducts and initiate carcinogenesis. Mixed exposures to coal dust (CD) and PAHs are common in occupational settings. In the CD and PAH-exposed lung, CD increases apoptosis and causes alveolar type II (AT-II) cell hyperplasia but reduces CYP1A1 induction. Inflammation, but not apoptosis, appears etiologically associated with reduced CYP1A1 induction in this mixed exposure model. Many AT-II cells in the CD-exposed lungs have no detectable CYP1A1 induction after PAH exposure. Although AT-II cells are a small subfraction of lung cells, they are believed to be a potential progenitor cell for some lung cancers. Because CYP1A1 is induced via ligand-mediated nuclear translocation of the aryl hydrocarbon receptor (AhR), we investigated the effect of CD on PAH-induced nuclear translocation of AhR in AT-II cells isolated from in vivo-exposed rats. Rats received CD or vehicle (saline) by intratracheal (IT) instillation. Three days before sacrifice, half of the rats in each group started daily intraperitoneal injections of the PAH, β-naphthoflavone (BNF). Results Fourteen days after IT CD exposure and 1 day after the last intraperitoneal BNF injection, AhR immunofluorescence indicated that proportional AhR nuclear expression and the percentage of cells with nuclear AhR were significantly increased in rats receiving IT saline and BNF injections compared to vehicle controls. However, in CD-exposed rats, BNF did not significantly alter the nuclear localization or cytosolic expression of AhR compared to rats receiving CD and oil. Conclusion Our findings suggest that during particle and PAH mixed exposures, CD alters the BNF-induced nuclear translocation of AhR in AT-II cells. This provides an explanation for the modification of CYP1A1 induction in these cells. Thus, this study suggests that mechanisms for reduced PAH-induced CYP1A1 activity in the CD exposed lung include not only the effects of inflammation on the lung as a whole, but also reduced PAH-associated nuclear translocation of AhR in an expanded population of AT-II cells. PMID:19650907

Overexpression of Selenoprotein SelK in BGC-823 Cells Inhibits Cell Adhesion and Migration.

PubMed

Ben, S B; Peng, B; Wang, G C; Li, C; Gu, H F; Jiang, H; Meng, X L; Lee, B J; Chen, C L

2015-10-01

Effects of human selenoprotein SelK on the adhesion and migration ability of human gastric cancer BGC-823 cells using Matrigel adhesion and transwell migration assays, respectively, were investigated in this study. The Matrigel adhesion ability of BGC-823 cells that overexpressed SelK declined extremely significantly (p < 0.01) compared with that of the cells not expressing the protein. The migration ability of BGC-823 cells that overexpressed SelK also declined extremely significantly (p < 0.01). On the other hand, the Matrigel adhesion ability and migration ability of the cells that overexpressed C-terminally truncated SelK did not decline significantly. The Matrigel adhesion ability and migration ability of human embryonic kidney HEK-293 cells that overexpressed SelK did not show significant change (p > 0.05) with the cells that overexpressed the C-terminally truncated protein. In addition to the effect on Matrigel adhesion and migration, the overexpression of SelK also caused a loss in cell viability (as measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) colorimetric assay) and induced apoptosis as shown by confocal microscopy and flow cytometry. The cytosolic free Ca2+ level of these cells was significantly increased as detected by flow cytometry. But the overexpression of SelK in HEK-293 cells caused neither significant loss in cell viability nor apoptosis induction. Only the elevation of cytosolic free Ca2+ level in these cells was significant. Taken together, the results suggest that the overexpression of SelK can inhibit human cancer cell Matrigel adhesion and migration and cause both the loss in cell viability and induction of apoptosis. The release of intracellular Ca2+ from the endoplasmic reticulum might be a mechanism whereby the protein exerted its impact. Furthermore, only the full-length protein, but not C-terminally truncated form, was capable of producing such impact. The embryonic cells were not influenced by the elevation of free Ca2+ level in cytosol, probably due to their much greater tolerance to the variation.

Power Quality Improvement in Induction Furnace by Harmonic Reduction Using Dynamic Voltage Restorer

NASA Astrophysics Data System (ADS)

Saggu, Tejinder Singh; Singh, Lakhwinder

2016-06-01

Induction furnaces are used in wide quantity under different capacities for annual production of around 25 million tons of iron and steel in India. It plays a vital role in various manufacturing processes around the world for melting different types of metal scraps i. e. Copper, Cast Iron, Aluminium, Steel, Brass, Bronze, Silicon, Gold, Silver etc. which are further used in many other industrial applications. The induction furnace causes a huge disturbance to the utility and nearby consumers during its operation due to its non-linear characteristics. This is a serious phenomenon responsible for power quality degradation in the power system. This paper presents methodology to improve the power quality degradation caused by induction furnace using Dynamic Voltage Restorer (DVR) which is a type of custom power device. The real time data has been taken from an industry employing induction furnace for production of ingots from scrap material. The experimental readings are measured using power quality analyser equipment. The simulation of whole plant is done by analysing this same data and the simulation results are compared with actual onsite results. Then, solution methodology using DVR is presented which revealed that the implementation of DVR is an effective solution for voltage sag mitigation and harmonics improvement in induction furnace.

Induction heating of planetary interiors

NASA Astrophysics Data System (ADS)

Kislyakova, K.; Noack, L.; Johnstone, C. P.; Zaitsev, V. V.; Fossati, L.; Lammer, H.; Khodachenko, M. L.; Odert, P.; Güdel, M.

2017-09-01

We present a calculation of the energy release in planetary interiors caused by induction heating. If an exoplanet orbits a host star with a strong magnetic field, it will be embedded in periodically varying magnetic environment. In our work, we consider only a dipole field of the host star and assume the dipole axis to be inclined with respect to the stellar rotational axis, which causes the magnetic field to vary. In this case, the varying magnetic field surrounding the planet will generate induction currents inside the planetary mantle, which will dissipate in the planetary interiors. We show that this energy release can be very substantial and in some cases even lead to complete melting of the planetary mantle over geological timescales, accompanied by the enhanced magnetic activity.

MCP-1 causes cardiomyoblast death via autophagy resulting from ER stress caused by oxidative stress generated by inducing a novel zinc-finger protein, MCPIP.

PubMed

Younce, Craig W; Kolattukudy, Pappachan E

2010-01-27

MCP-1 (monocyte chemotactic protein-1) plays a critical role in the development of heart failure that is known to involve apoptosis. How MCP-1 contributes to cell death involved in the development of heart disease is not understood. In the present study we show that MCP-1 causes death in cardiac myoblasts, H9c2 cells, by inducing oxidative stress which causes ER stress leading to autophagy via a novel zinc-finger protein, MCPIP (MCP-1-induced protein). MCPIP expression caused cell death, and knockdown of MCPIP attenuated MCP-1-induced cell death. It caused induction of iNOS (inducible NO synthase), translocation of the NADPH oxidase subunit phox47 from the cytoplasm to the membrane, production of ROS (reactive oxygen species), and induction of ER (endoplasmic reticulum) stress markers HSP40 (heat-shock protein 40), PDI (protein disulfide-isomerase), GRP78 (guanine-nucleotide-releasing protein 78) and IRE1alpha (inositol-requiring enzyme 1alpha). It also caused autophagy, as indicated by beclin-1 induction, cleavage of LC3 (microtubule-associated protein 1 light chain 3) and autophagolysosome formation, and apoptosis, as indicated by caspase 3 activation and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) assay. Inhibitors of oxidative stress, including CeO2 nanoparticles, inhibited ROS formation, ER stress, autophagy and cell death. Specific inhibitors of ER stress inhibited autophagy and cell death as did knockdown of the ER stress signalling protein IRE1. Knockdown of beclin-1 and autophagy inhibitors prevented cell death. This cell death involved caspase 2 and caspase 12, as specific inhibitors of these caspases prevented MCPIP-induced cell death. Microarray analysis showed that MCPIP expression caused induction of a variety of genes known to be involved in cell death. MCPIP caused activation of JNK (c-Jun N-terminal kinase) and p38 and induction of p53 and PUMA (p53 up-regulated modulator of apoptosis). Taken together, these results suggest that MCPIP induces ROS/RNS (reactive nitrogen species) production that causes ER stress which leads to autophagy and apoptosis through caspase 2/12 and IRE1alpha-JNK/p38-p53-PUMA pathway. These results provide the first molecular insights into the mechanism by which elevated MCP-1 levels associated with chronic inflammation may contribute to the development of heart failure.

Catabolite Repression of Tryptophanase in Escherichia coli

PubMed Central

Botsford, James L.; DeMoss, R. D.

1971-01-01

Catabolite repression of tryptophanase was studied in detail under various conditions in several strains of Escherichia coli and was compared with catabolite repression of β-glactosidase. Induction of tryptophanase and β-galactosidase in cultures grown with various carbon sources including succinate, glycerol, pyruvate, glucose, gluconate, and arabinose is affected differently by the various carbon sources. The extent of induction does not seem to be related to the growth rate of the culture permitted by the carbon source during the course of the experiment. In cultures grown with glycerol as carbon source, preinduced for β-galactosidase or tryptophanase and made permeable by ethylenediaminetetraacetic acid (EDTA) treatment, catabolite repression of tryptophanase was not affected markedly by the addition of cAMP (3′,5′-cyclic adenosine monophosphate). Catabolite repression by glucose was only partially relieved by the addition of cAMP. In contrast, under the same conditions, cAMP completely relieved catabolite repression of β-galactosidase by either pyruvate or glucose. Under conditions of limited oxygen, induction of tryptophanase is sensitive to catabolite repression; under the same conditions, β-galactosidase induction is not sensitive to catabolite repression. Induction of tryptophanase in cells grown with succinate as carbon source is sensitive to catabolite repression by glycerol and pyruvate as well as by glucose. Studies with a glycerol kinaseless mutant indicate that glycerol must be metabolized before it can cause catabolite repression. The EDTA treatment used to make the cells permeable to cAMP was found to affect subsequent growth and induction of either β-galactosidase or tryptophanase much more adversely in E. coli strain BB than in E. coli strain K-12. Inducation of tryptophanase was reduced by the EDTA treatment significantly more than induction of β-galactosidase in both strains. Addition of 2.5 × 10−3m cAMP appeared partially to reverse the inhibitory effect of the EDTA treatment on enzyme induction but did not restore normal growth. PMID:4322348

Effects of Taxol plus radiation on the apoptotic and mitotic indices of mouse intestinal crypt cells.

PubMed

Ozkan, L; Ozuysal, S; Egeli, U; Adim, S B; Tunca, B; Aydemir, N; Ceçener, G; Ergül, E; Akpinar, G; Cimen, C; Engin, K; Ahmed, M M

2001-07-01

In this study we investigated the effect of Taxol, radiation, or Taxol plus radiation on highly proliferative normal tissue--the intestinal crypt cells of Swiss albino mice. Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered by bolus intravenously through the tail vein. Radiation was given using a linear accelerator. There were four treatment categories, which comprised a total of 34 groups. Each group consisted of five animals. The first category was a control category which comprised one group (n = 5). The second treatment category was Taxol alone which comprised three groups (n = 15). The third treatment category was radiation alone which comprised three groups (n = 15). The fourth treatment category was Taxol plus radiation which comprised 27 groups (n = 135). Mice were killed 24 h after Taxol or radiation or combined administration using ether anesthesia. Using a light microscope, apoptotic and mitotic indices were counted on jejunal crypt cells of mice that were stained with hematoxylin-eosin. Differences between groups were statistically evaluated with Student's t-test. Taxol caused a dose-dependent increase in apoptosis (P = 0.045) and decreased the mitotic index (P = 0.006) at high doses. Similarly, radiation caused a dose-dependent increase in apoptosis (P = 0.046) and decreased the mitotic index (P = 0.299) at higher radiation doses. Compared to radiation alone, Taxol caused a significant induction of apoptosis (P = 0.010). In combination, no significant radiosensitizing effect of Taxol was observed (enhancement ratio < 1), when compared to radiation alone. However, an increase in apoptosis was observed after 24 h of Taxol exposure when compared to 12 or 48 h of Taxol exposure (P = 0.0001 and P = 0.0001). These findings suggest that Taxol did not cause a radiosensitizing effect in intestinal crypt cells. However, a 24-hour pretreatment of Taxol exposure followed by radiation caused significant induction of apoptosis and reduction of the mitotic index when compared to other Taxol timing sequences. Thus, the lack of a radiosensitizing effect of Taxol in these proliferative cells may be due to enhanced mitotic death rather than apoptotic death.

Laser vocal cordectomy fails to effectively reduce respiratory noise in horses with laryngeal hemiplegia.

PubMed

Brown, Jennifer A; Derksen, Frederik J; Stick, John A; Hartmann, William M; Robinson, N Edward

2005-01-01

To report the effect of unilateral laser vocal cordectomy on respiratory noise and airway function in horses with experimentally induced laryngeal hemiplegia (LH). Experimental study. Six Standardbred horses without upper airway abnormalities at rest or during high-speed treadmill exercise. Respiratory sounds and inspiratory trans-upper airway pressure (P(Ui)) were measured before (baseline) and 14 days after induction of LH by left recurrent laryngeal neurectomy, and again 30, 60, 90, and 120 days after endoscopically assisted laser cordectomy of the left vocal cord. Data were collected with the horses exercising on a treadmill at a speed producing maximum heart rate (HR(max)). In horses exercising at HR(max), induction of LH caused a significant increase in P(Ui), sound level (SL), and the sound intensity of formant 2 (F(2)) and 3 (F(3)). The sound intensity of formant 1 (F(1)) was unaffected by induction of LH. Laser vocal cordectomy had no effect on SL, or on the sound intensity of F(1) and F(3). At 30, 60, 90, and 120 days after surgery, P(Ui) and the sound intensity of F(2) were significantly reduced, but these variables remained significantly different from baseline values. Unilateral laser vocal cordectomy did not effectively improve upper airway noise in horses with LH. The procedure decreased upper airway obstruction to the same degree as bilateral ventriculocordectomy. Currently, laser vocal cordectomy cannot be recommended for the treatment of upper airway noise in horses with LH.

Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koo, Hyun-Young; Miyashita, Michio; Department of Pediatrics, Nihon University School of Medicine, Itabashi, Tokyo

2009-12-11

Diets high in fructose cause hypertriglyceridemia and insulin resistance in part due to simultaneous induction of gluconeogenic and lipogenic genes in liver. We investigated the mechanism underlying the unique pattern of gene induction by dietary fructose. Male Sprague-Dawley rats (n = 6 per group) were meal-fed (4 h/d) either 63% (w/w) glucose or 63% fructose diet. After two weeks, animals were killed at the end of the last meal. Nuclear SREBP-1 was 2.2 times higher in fructose-fed rats than glucose-fed rats. Nuclear FoxO1 was elevated 1.7 times in fructose group, but did not reach significance (P = 0.08). Unexpectedly, nomore » difference was observed in nuclear ChREBP between two groups. However, ChREBP DNA binding was 3.9x higher in fructose-fed animals without an increase in xylulose-5-phospate, a proposed ChREBP activator. In conclusion, the gene induction by dietary fructose is likely to be mediated in part by simultaneously increased ChREBP activity, SREBP-1 and possibly FoxO1 protein in nucleus.« less

A computational simulation of long-term synaptic potentiation inducing protocol processes with model of CA3 hippocampal microcircuit.

PubMed

Świetlik, D; Białowąs, J; Kusiak, A; Cichońska, D

2018-01-01

An experimental study of computational model of the CA3 region presents cog-nitive and behavioural functions the hippocampus. The main property of the CA3 region is plastic recurrent connectivity, where the connections allow it to behave as an auto-associative memory. The computer simulations showed that CA3 model performs efficient long-term synaptic potentiation (LTP) induction and high rate of sub-millisecond coincidence detection. Average frequency of the CA3 pyramidal cells model was substantially higher in simulations with LTP induction protocol than without the LTP. The entropy of pyramidal cells with LTP seemed to be significantly higher than without LTP induction protocol (p = 0.0001). There was depression of entropy, which was caused by an increase of forgetting coefficient in pyramidal cells simulations without LTP (R = -0.88, p = 0.0008), whereas such correlation did not appear in LTP simulation (p = 0.4458). Our model of CA3 hippocampal formation microcircuit biologically inspired lets you understand neurophysiologic data. (Folia Morphol 2018; 77, 2: 210-220).

Eddy-Current Sensors with Asymmetrical Point Spread Function

PubMed Central

Gajda, Janusz; Stencel, Marek

2016-01-01

This paper concerns a special type of eddy-current sensor in the form of inductive loops. Such sensors are applied in the measuring systems classifying road vehicles. They usually have a rectangular shape with dimensions of 1 × 2 m, and are installed under the surface of the traffic lane. The wide Point Spread Function (PSF) of such sensors causes the information on chassis geometry, contained in the measurement signal, to be strongly averaged. This significantly limits the effectiveness of the vehicle classification. Restoration of the chassis shape, by solving the inverse problem (deconvolution), is also difficult due to the fact that it is ill-conditioned. An original approach to solving this problem is presented in this paper. It is a hardware-based solution and involves the use of inductive loops with an asymmetrical PSF. Laboratory experiments and simulation tests, conducted with models of an inductive loop, confirmed the effectiveness of the proposed solution. In this case, the principle applies that the higher the level of sensor spatial asymmetry, the greater the effectiveness of the deconvolution algorithm. PMID:27782033

Eddy-Current Sensors with Asymmetrical Point Spread Function.

PubMed

Gajda, Janusz; Stencel, Marek

2016-10-04

This paper concerns a special type of eddy-current sensor in the form of inductive loops. Such sensors are applied in the measuring systems classifying road vehicles. They usually have a rectangular shape with dimensions of 1 × 2 m, and are installed under the surface of the traffic lane. The wide Point Spread Function (PSF) of such sensors causes the information on chassis geometry, contained in the measurement signal, to be strongly averaged. This significantly limits the effectiveness of the vehicle classification. Restoration of the chassis shape, by solving the inverse problem (deconvolution), is also difficult due to the fact that it is ill-conditioned. An original approach to solving this problem is presented in this paper. It is a hardware-based solution and involves the use of inductive loops with an asymmetrical PSF. Laboratory experiments and simulation tests, conducted with models of an inductive loop, confirmed the effectiveness of the proposed solution. In this case, the principle applies that the higher the level of sensor spatial asymmetry, the greater the effectiveness of the deconvolution algorithm.

Evaluation of on-line desalter-inductively coupled plasma-mass spectrometry system for determination of Cr(III), Cr(VI), and total chromium concentrations in natural water and urine samples

NASA Astrophysics Data System (ADS)

Sun, Y. C.; Lin, C. Y.; Wu, S. F.; Chung, Y. T.

2006-02-01

We have developed a simple and convenient method for the determination of Cr(III), Cr(VI), and the total chromium concentrations in natural water and urine samples that use a flow injection on-line desalter-inductively coupled plasma-mass spectrometry system. When using aqueous ammonium chloride (pH 8) as the stripping solution, the severe interference from sodium in the matrix can be eliminated prior to inductively coupled plasma-mass spectrometry measurement, and the Cr(VI) level can be determined directly. To determine the total concentration of Cr in natural water and urine samples, we used H 2O 2 or HNO 3 to decompose the organic matter and convert all chromium species into the Cr(VI) oxidation state. To overcome the spectral interference caused by the matrix chloride ion in the resulting solutions, we employed cool plasma to successfully suppress chloride-based molecular ion interference during the inductively coupled plasma-mass spectrometry measurement. By significantly eliminating interference from the cationic and anionic components in the matrices prior to the inductively coupled plasma-mass spectrometry measurement, we found that the detection limit reached 0.18 μg L - 1 (based on 3 sigma). We validated this method through the analysis of the total chromium content in two reference materials (NIST 1643c and 2670E) and through measuring the recovery in spiked samples.

Apoptosis induction is involved in UVA-induced autolysis in sea cucumber Stichopus japonicus.

PubMed

Qi, Hang; Fu, Hui; Dong, Xiufang; Feng, Dingding; Li, Nan; Wen, Chengrong; Nakamura, Yoshimasa; Zhu, Beiwei

2016-05-01

Autolysis easily happens to sea cucumber (Stichopus japonicus, S. japonicus) for external stimulus like UV exposure causing heavy economic losses. Therefore, it is meaningful to reveal the mechanism of S. japonicas autolysis. In the present study, to examine the involvement of apoptosis induction in UVA-induced autolysis of S. japonicas, we investigated the biochemical events including the DNA fragmentation, caspase-3 activation, mitogen-activated protein kinases (MAPKs) phosphorylation and free radical formation. Substantial morphological changes such as intestine vomiting and dermatolysis were observed in S. japonicus during the incubation after 1-h UVA irradiation (10W/m(2)). The degradation of the structural proteins and enhancement of cathepsin L activity were also detected, suggesting the profound impact of proteolysis caused by the UVA irradiation even for 1h. Furthermore, the DNA fragmentation and specific activity of caspase-3 was increased up to 12h after UVA irradiation. The levels of phosphorylated p38 mitogen activated protein kinase (MAPK) and phosphorylated c-Jun.-N-terminal kinase (JNK) were significantly increased by the UVA irradiation for 1h. An electron spin resonance (ESR) analysis revealed that UVA enhanced the free radical formation in S. japonicas, even through we could not identify the attributed species. These results suggest that UVA-induced autolysis in S. japonicas at least partially involves the oxidative stress-sensitive apoptosis induction pathway. These data present a novel insight into the mechanisms of sea cucumber autolysis induced by external stress. Copyright © 2016 Elsevier B.V. All rights reserved.

System and method of adjusting the equilibrium temperature of an inductively-heated susceptor

DOEpatents

Matsen, Marc R; Negley, Mark A; Geren, William Preston

2015-02-24

A system for inductively heating a workpiece may include an induction coil, at least one susceptor face sheet, and a current controller coupled. The induction coil may be configured to conduct an alternating current and generate a magnetic field in response to the alternating current. The susceptor face sheet may be configured to have a workpiece positioned therewith. The susceptor face sheet may be formed of a ferromagnetic alloy having a Curie temperature and being inductively heatable to an equilibrium temperature approaching the Curie temperature in response to the magnetic field. The current controller may be coupled to the induction coil and may be configured to adjust the alternating current in a manner causing a change in at least one heating parameter of the susceptor face sheet.

[Nevirapine induces abstinence symptoms in patients on a methadone maintenance program with HIV infection].

PubMed

Baño Rodrigo, M D; Agujetas Rodríguez, M; López García, M L; Guillén Llera, J L

2000-01-01

The objective of this study was to investigate the potential inductive effect of nevirapine (NVP) with methadone. Eight patients on the methadone maintenance programme with anti-retroviral therapy because of their infection with HIV, well maintained with methadone and without symptoms of abstinence were studied. All were included in a study of measurement of plasma levels of methadone. Anti-retroviral medication was changed, including NVP, and patients began with symptoms of abstinence 5 to 10 days later. Our results indicate an inductive effect of NVP on the methadone metabolism which caused symptoms of abstinence in all patients, which prompted an increase in the dose and plasma concentration of methadone was lost; patients continued with significantly low plasma levels (p < 0.01) after a therapy mean duration of 6.5 months, with no full recovery.

Characterization of Mouse Models of Early Pancreatic Lesions Induced by Alcohol and Chronic Pancreatitis.

PubMed

Xu, Shiping; Chheda, Chintan; Ouhaddi, Yassine; Benhaddou, Hajar; Bourhim, Mouloud; Grippo, Paul J; Principe, Daniel R; Mascariñas, Emman; DeCant, Brian; Tsukamoto, Hidekazu; Pandol, Stephen J; Edderkaoui, Mouad

2015-08-01

We describe the first mouse model of pancreatic intraepithelial neoplasia (PanIN) lesions induced by alcohol in the presence and absence of chronic pancreatitis. Pdx1-Cre;LSL-K-ras mice were exposed to Lieber-DeCarli alcohol diet for 6 weeks with cerulein injections. The PanIN lesions and markers of fibrosis, inflammation, histone deacetylation, epithelial-to-mesenchymal transition (EMT), and cancer stemness were measured by immunohistochemistry and Western. Exposure of Pdx1-Cre;LSL-K-ras mice to an alcohol diet significantly stimulated fibrosis and slightly but not significantly increased the level of PanIN lesions associated with an increase in tumor-promoting M2 macrophages. Importantly, the alcohol diet did not increase activation of stellate cells. Alcohol diet and cerulein injections resulted in synergistic and additive effects on PanIN lesion and M2 macrophage phenotype induction, respectively. Cerulein pancreatitis caused stellate cell activation, EMT, and cancer stemness in the pancreas. Pancreatitis caused histone deacetylation, which was promoted by the alcohol diet. Pancreatitis increased EMT and cancer stemness markers, which were not further affected by the alcohol diet. The results suggest that alcohol has independent effects on promotion of PDAC associated with fibrosis formed through a stellate cell-independent mechanism and that it further promotes early PDAC and M2 macrophage induction in the context of chronic pancreatitis.

Experimentally induced hyperthyroidism influences oxidant and antioxidant status and impairs male gonadal functions in adult rats.

PubMed

Asker, M E; Hassan, W A; El-Kashlan, A M

2015-08-01

The objective of the present experiment was to study the effect of hyperthyroidism on male gonadal functions and oxidant/antioxidant biomarkers in testis of adult rats. Induction of hyperthyroidism by L-thyroxine (L-T4, 300 μg kg(-1) body weight) treatment once daily for 3 or 8 weeks caused a decrease in body weight gain as well as in absolute genital sex organs weight. The epididymal sperm counts and their motility were significantly decreased in a time-dependent manner following L-T4 treatment. Significant decline in serum levels of luteinising hormone, follicle stimulating hormone and testosterone along with significant increase in serum estradiol level was observed in hyperthyroid rats compared with euthyroid ones. Significant increase in malondialdehyde and nitric oxide concentration associated with significant decrease in superoxide dismutase and catalase activity was also noticed following hyperthyroidism induction. Both reduced glutathione content and glutathione peroxidase activity were increased in hyperthyroid rats compared with control rats. Marked histopathological alterations were observed in testicular section of hyperthyroid rats. These results provide evidence that hypermetabolic state induced by excess level of thyroid hormones may be a causative factor for the impairment of testicular physiology as a consequence of oxidative stress. © 2014 Blackwell Verlag GmbH.

Vinclozolin, a widely used fungizide, enhanced BaP-induced micronucleus formation in human derived hepatoma cells by increasing CYP1A1 expression.

PubMed

Wu, Xin-Jiang; Lu, Wen-qing; Roos, Peter H; Mersch-Sundermann, Volker

2005-10-15

Vinclozolin, a widely used fungicide, can be identified as a residue in numerous vegetable and fruit samples. To get insight in its genetic toxicity, we investigated the genotoxic effect of vinclozolin in the human derived hepatoma cell line HepG2 using the micronucleus (MN) assay. Additionally, to evaluate the co- or anti-mutagenic potency of vinclozolin, we treated HepG2 cells with different concentrations of vinclozolin for 24 h. Subsequently, the cells were exposed to benzo[a]pyrene (BaP) for 1h. Exposure of HepG2 cells to 50-400 microM vinclozolin alone did not cause any induction of micronuclei. However, a pronounced co-mutagenic effect was observed. MN frequencies caused by BaP increased by 30.6%, 52.8% and 65.3% after pretreatment of the cell cultures with 50, 100 and 200 microM vinclozolin, respectively. The highest concentration (400 microM) of vinclozolin tested caused cytotoxicity. Therefore, micronuclei were not considered for that concentration. To clarify the mechanism of cogenotoxicity, we assayed cytochrome P450 1A1 (CYP1A1), which plays a pivotal role in activation of BaP. Cells exposed to vinclozolin led to significant increase of CYP1A1 expression in Western blot. The result suggested that induction of CYP1A1 by vinclozolin account for its enhancing effect on genotoxicity caused by BaP.

Advanced Welding Tool

NASA Technical Reports Server (NTRS)

1982-01-01

Accutron Tool & Instrument Co.'s welder was originally developed as a tool specifically for joining parts made of plastic or composite materials in any atmosphere to include the airless environment of space. Developers decided on induction or magnetic heating to avoid causing deformation and it also can be used with almost any type of thermoplastic material. Induction coil transfers magnetic flux through the plastic to a metal screen that is sandwiched between the sheets of plastic to be joined. When welder is energized, alternating current produces inductive heating on the screen causing the adjacent plastic surfaces to melt and flow into the mesh, creating a bond on the total surface area. Dave Brown, owner of Great Falls Canoe and Kayak Repair, Vienna, VA, uses a special repair technique based on operation of the Induction Toroid Welder to fix canoes. Whitewater canoeing poses the problem of frequent gashes that are difficult to repair. The main reason is that many canoes are made of plastics. The commercial Induction model is a self-contained, portable welding gun with a switch on the handle to regulate the temperature of the plastic melting screen. Welder has a broad range of applications in the automobile, appliance, aerospace and construction industries.

Depot-specific characteristics of adipose tissue-derived stromal cells in thyroid-associated orbitopathy.

PubMed

Wong, Janice Siu Chong; Chu, Wai Kit; Li, Benjamin Fuk-Loi; Pang, Chi-Pui; Chong, Kelvin Kam-Lung

2018-04-17

Thyroid-associated orbitopathy (TAO) causes inflammatory fibroproliferation of periocular connective tissues. We compared adipose tissue-derived stem/stromal cells (ADSCs) from three adipose depots of each patient with TAO on mesenchymal, myofibrogenic, adipogenic properties and associated hyaluronan (HA) synthesis. ADSCs were generated from periocular (eyelid, orbital) and subcutaneous (abdominal) adipose tissues of three patients with TAO. Mesenchymal markers were characterised by reverse transcription-PCR and immunofluorescent staining. A 3-week adipogenic induction was evaluated by Nile red staining and quantitative PCR (qPCR) of peroxisome proliferator-activated receptor (PPARγ), adiponectin and hyaluronan synthase (HAS)-2. A 7-day myofibrogenic induction was assayed by immunofluorescent staining and qPCR of α-smooth muscle actin (α-SMA). ADSCs from all depots expressed similar levels of mesenchymal markers CD44, CD90 and CD105 (p=0.288, p=0.43 and p=0.837, respectively). After adipogenic induction, intracellular lipid increased for more than 32% and PPARγ mRNA showed more than twofold increase from all three depots. However, adiponectin and HAS-2 mRNA levels were significantly higher in the eyelid and orbital ADSCs than those from the subcutaneous ADSCs after induction (2.4×10 7 , 3.9×10 6  folds vs below detection limit; 63.3-fold, 26.1-fold, vs 33% reduction, respectively; all p=0.002). Significantly more myofibroblasts and higher mRNA level of α-SMA were obtained from the orbital and eyelid compared with the subcutaneous ADSCs during myofibrogenic induction (80.2%, 70.6% vs 29.3%; 30.2-fold, 24.2-fold vs 1.7-fold, respectively; all p=0.002). ADSCs from different adipose depots of the same donors exhibited similar mesenchymal phenotypes but differed significantly in adipogenic, myofibrogenic potentials and associated HA synthesis. These depot-specific characteristics of ADSCs may contribute to site-specific adipose tissue involvement in TAO. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Geophysical Interpretation of Induction Arrows Observed at Jeju Island, Korea

NASA Astrophysics Data System (ADS)

Yang, J.; Choi, H.

2015-12-01

Jeju Island, a volcanic island located on the continental margin in the southern end of the Korean Peninsula, has been paid a special attention to geological and geophysical society for a long time due to its tectonic importance associated with the volcanism of the island. In this study, we try to interpret induction arrows observed at the island that have been estimated from broad-band magnetotelluric (MT) data and existing magnetovariational data, which are sensitive to lateral conductivity distribution of the Earth. Overall pattern of observed induction arrows is clearly frequency-dependent: perpendicular to nearby coastline of the observation site for higher frequencies than 0.1 Hz but rotating toward south or southeastern direction for lower frequency than 0.01 Hz. Furthermore, induction arrows at frequencies lower than 0.001 Hz, which derived from the existing magnetovariational data, point to the south or the southeast as well. In order to examine whether observed induction arrows can be explained by only surrounding seas, 3-D MT modeling considering seas surrounding the island is carried out. The results demonstrate that induction arrows at higher frequencies than 0.01 Hz can be explained well by the surrounding seas but for lower frequencies than 0.01 Hz there are significant discrepancies between observed and calculated arrows. This strongly implies the existence of deep-seated conductor located beneath the farther south of the island, namely, the East China Sea. The existence of this deep-seated conductor can be supported by other previous geophysical studies, which is likely to be caused by mantle upwelling derived from shear traction of horizontal mantle flow in tensional back arc of Kyushu Island, Japan.

The effect of the inductive electric field on ion poloidal rotation in all collisionality regimes for the primary ions in tokamaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pan Chengkang; Wang Shaojie; Institute of Plasma Physics, Chinese Academy of Sciences, Hefei, 230031

2007-11-15

The expression for the poloidal rotation velocity of the primary ions that is caused by the parallel inductive electric field in tokamaks and valid in all collisionality regimes is derived via the Hirshman-Sigmar moment approach. Also the expression of the collisional impurity ions poloidal rotation velocity that is caused by the parallel inductive electric field in tokamaks is derived. The poloidal rotation velocities of the primary ions and the impurity ions are sensitive to the primary ion collisionality parameter and the impurity strength parameter. The poloidal rotation velocities of the primary ions and the impurity ions decrease with the primarymore » ion collisionality parameter and decrease with the impurity strength parameter.« less

Induction of the unfolded protein response by constitutive G-protein signaling in rod photoreceptor cells.

PubMed

Wang, Tian; Chen, Jeannie

2014-10-17

Phototransduction is a G-protein signal transduction cascade that converts photon absorption to a change in current at the plasma membrane. Certain genetic mutations affecting the proteins in the phototransduction cascade cause blinding disorders in humans. Some of these mutations serve as a genetic source of "equivalent light" that activates the cascade, whereas other mutations lead to amplification of the light response. How constitutive phototransduction causes photoreceptor cell death is poorly understood. We showed that persistent G-protein signaling, which occurs in rod arrestin and rhodopsin kinase knock-out mice, caused a rapid and specific induction of the PERK pathway of the unfolded protein response. These changes were not observed in the cGMP-gated channel knock-out rods, an equivalent light condition that mimics light-stimulated channel closure. Thus transducin signaling, but not channel closure, triggers rapid cell death in light damage caused by constitutive phototransduction. Additionally, we show that in the albino light damage model cell death was not associated with increase in global protein ubiquitination or unfolded protein response induction. Taken together, these observations provide novel mechanistic insights into the cell death pathway caused by constitutive phototransduction and identify the unfolded protein response as a potential target for therapeutic intervention. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Silicon influence on resistance induction against Bemisia tabaci biotype B (Genn.) (Hemiptera: Aleyrodidae) and on vegetative development in two soybean cultivars.

PubMed

Ferreira, R S; Moraes, J C; Antunes, C S

2011-01-01

The potential of populations of Bemisia tabaci (Genn.) to become resistant to insecticides has stimulated research into alternative tactics of integrated pest management such as the induction of host-plant resistance. Recent data have shown that silicon can increase the degree of resistance of host plants to insect pests. Therefore the aim of our work was to study the effects of silicon application on the vegetative development of soybean plants and on the induction of resistance to the silverleaf whitefly, B. tabaci biotype B. We performed choice and no-choice tests of oviposition preference on two soybean cultivars, IAC-19 (moderately resistant to B. tabaci biotype B) and MONSOY-8001 (susceptible), with and without application of silicon. Silicon did not affect silverleaf whitefly oviposition preferences, but caused significant mortality in nymphs. Thus, silicon increased the degree of resistance to silverleaf whitefly. Silicon decreased the production of phenolic compounds, but did not affect lignin production. However, when applied to cultivar IAC-19, it increased the production of non-protein organic nitrogen. Silicon had no effect on the vegetative development of soybean plants, but it increased the degree of resistance to the silverleaf whitefly. We conclude that silicon applications combined with cultivar IAC-19 can significantly decrease silverleaf whitefly populations, having a positive impact both on the soybean plant and on the environment.

Comparison of Pathogenesis and Host Immune Responses to Candida glabrata and Candida albicans in Systemically Infected Immunocompetent Mice

PubMed Central

Brieland, Joan; Essig, David; Jackson, Craig; Frank, Doyle; Loebenberg, David; Menzel, Fred; Arnold, Brian; DiDomenico, Beth; Hare, Roberta

2001-01-01

Cytokine-mediated host defense against Candida glabrata infection was compared to that against C. albicans, using immunocompetent murine models of systemic candidiasis. The pathogenesis of infection was evaluated morphologically and by culture of target organs, while the kinetics of induction of cytokine mRNAs and corresponding proteins were determined in kidneys by real-time reverse transcription-PCR and cytokine-specific murine enzyme-linked immunosorbent assays, respectively. Systemic infection with C. glabrata resulted in a chronic, nonfatal infection with recovery of organisms from kidneys, while intravenous inoculation with C. albicans resulted in rapid mortality with logarithmic growth of organisms in kidneys and recovery of C. albicans from the spleen, liver, and lungs. Survival of C. glabrata-infected mice was associated with rapid induction of mRNAs and corresponding immunoreactive proteins for the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and gamma interferon (IFN-γ) and the lack of induction of protein for the anti-inflammatory cytokine IL-10. In contrast, mortality in C. albicans-infected mice was associated with induction of mRNA and corresponding protein for IL-10 but delayed (i.e., TNF-α) or absent (i.e., IL-12 and IFN-γ) induction of immunoreactive proinflammatory cytokines. Mice were subsequently treated with cytokine-specific neutralizing monoclonal antibodies (MAbs) to TNF-α, IL-12, or IFN-γ, and the effect on growth of C. glabrata in kidneys was assessed. Neutralization of endogenous TNF-α resulted in a significant increase in C. glabrata organisms compared to similarly infected mice administered an isotype-matched control MAb, while neutralization of endogenous IL-12 or IFN-γ had no significant effect on C. glabrata replication. These results demonstrate that in response to intravenous inoculation of C. glabrata, immunocompetent mice develop chronic nonfatal renal infections which are associated with rapid induction of the proinflammatory cytokines TNF-α, IL-12, and IFN-γ. Furthermore, TNF-α plays a key role in host defense against systemic candidiasis caused by either C. glabrata or C. albicans, as the absence of endogenous TNF-α activity was associated with enhanced tissue burden in both infection models. PMID:11447185

Defect of Adaptation to Hypoxia in Patients With COPD Due to Reduction of Histone Deacetylase 7

PubMed Central

To, Masako; Yamamura, Satoshi; Akashi, Kenichi; Charron, Catherine E.; Barnes, Peter J.

2012-01-01

Background: Hypoxia inducible factor (HIF)-1 plays an important role in cellular adaptation to hypoxia by activating oxygen-regulated genes such as vascular endothelial growth factor (VEGF) and erythropoietin. Sputum VEGF levels are reported to be decreased in COPD, despite hypoxia. Here we show that patients with COPD fail to induce HIF-1α and VEGF under hypoxic condition because of a reduction in histone deacetylase (HDAC) 7. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from patients with moderate to severe COPD (n = 21), smokers without COPD (n = 12), and nonsmokers (n = 15). PBMCs were exposed to hypoxia (1% oxygen, 5% CO2, and 94% N2) for 24 h, and HIF-1α and HDAC7 protein expression in nuclear extracts were determined by sodium dodecyl sulfate poly acrylamide gel electrophoresis (SDS-PAGE)/Western blotting. Results: HIF-1α was significantly induced by hypoxia in each group when compared with the normoxic condition (12-fold induction in nonsmokers, 24-fold induction in smokers without COPD, fourfold induction in COPD), but induction of HIF-1α under hypoxia was significantly lower in patients with COPD than in nonsmokers and smokers without COPD (P < .05 and P < .01, respectively). VEGF messenger RNA detected by quantitative real-time polymerase chain reaction was correlated with HIF-1α protein in nuclei (r = 0.79, P < .05), and HDAC7 protein expression was correlated with HIF-1α protein in nuclei (r = 0.46, P < .05). HDAC7 knockdown inhibited hypoxia-induced HIF-1α activity in U937 cells, and HIF-1α nuclear translocation and HIF-1α binding to the VEGF promoter in A549 cells. Conclusions: HDAC7 reduction in COPD causes a defect of HIF-1α induction response to hypoxia with impaired VEGF gene expression. This poor cellular adaptation might play a role in the pathogenesis of COPD. PMID:22172637

Clinical and economic outcomes of rabbit antithymocyte globulin induction in adults who received kidney transplants from living unrelated donors and received cyclosporine-based immunosuppression.

PubMed

Miller, James T; Collins, Curtis D; Stuckey, Linda J; Luan, Fu L; Englesbe, Michael J; Magee, John C; Park, Jeong M

2009-10-01

To evaluate the efficacy, safety, and costs of rabbit antithymocyte globulin (TMG) induction in patients who received kidney transplants from living unrelated donors. Retrospective cohort study. Large academic medical center. Eighty-seven patients who received kidney transplants from living unrelated donors: 40 of the recipients underwent transplantation between January 1, 2003, and December 31, 2004, and did not receive TMG induction (no induction group); 47 underwent transplantation between January 1, 2005, and June 30, 2006, and received TMG induction (induction group). All patients received cyclosporine-based immunosuppression. Biopsy-proven acute rejection, posttransplantation complications, and inpatient hospital costs for the first 12 months after transplantation were compared between groups using standard univariate statistical analyses. Induction significantly decreased the occurrence of biopsy-proven acute rejection versus no induction (2% vs 48%, p<0.001). Fifty percent of rejection episodes in the no induction group required hospitalization, and 46% of rejection episodes required TMG treatment. Slightly elevated initial costs associated with TMG induction were offset by lower costs related to rejection treatment. Total inpatient costs for the 12 months after transplantation were comparable between the groups (no induction $66,038 vs induction $74,183, p>0.05). For the no induction versus induction groups, no significant differences in cytomegalovirus disease (5% vs 6%), malignancy (3% vs 2%), graft failures (5% vs 6%), mortality (5% vs 4%), and serum creatinine concentrations (mean +/- SD 1.4 +/- 0.3 vs 1.5 +/- 0.3 mg/dl) were observed at 12 months (p>0.05 for all comparisons). Five-day TMG induction effectively reduced the 1-year acute rejection rate without significantly increasing total inpatient costs or posttransplantation complications among recipients of kidney transplants from living unrelated donors.

Excitation of lateral habenula neurons as a neural mechanism underlying ethanol-induced conditioned taste aversion.

PubMed

Tandon, Shashank; Keefe, Kristen A; Taha, Sharif A

2017-02-15

The lateral habenula (LHb) has been implicated in regulation of drug-seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5 g kg -1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced the magnitude of lever press-evoked inhibition. Finally, firing rates were significantly higher during consumption of the devalued saccharin solution after CTA induction. Next, we studied sham- and LHb-lesioned rats in our operant CTA paradigm and found that LHb lesion significantly attenuated CTA effects in the operant task. Our data demonstrate the importance of LHb excitation in regulating expression of ethanol-induced aversion and suggest a mechanism for its role in modulating escalation of voluntary ethanol intake. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Excitation of lateral habenula neurons as a neural mechanism underlying ethanol‐induced conditioned taste aversion

PubMed Central

Keefe, Kristen A.; Taha, Sharif A.

2016-01-01

Key points The lateral habenula (LHb) has been implicated in regulation of drug‐seeking behaviours through aversion‐mediated learning.In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol‐induced conditioned taste aversion (CTA) to saccharin.Ethanol‐induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste.In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol‐induced CTA.Our results strongly suggest that excitation of LHb neurons is required for ethanol‐induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Abstract Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion‐mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol‐induced aversion, we recorded neural firing in the LHb of freely behaving, water‐deprived rats before and after an ethanol‐induced (1.5 g kg−1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol‐induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced the magnitude of lever press‐evoked inhibition. Finally, firing rates were significantly higher during consumption of the devalued saccharin solution after CTA induction. Next, we studied sham‐ and LHb‐lesioned rats in our operant CTA paradigm and found that LHb lesion significantly attenuated CTA effects in the operant task. Our data demonstrate the importance of LHb excitation in regulating expression of ethanol‐induced aversion and suggest a mechanism for its role in modulating escalation of voluntary ethanol intake. PMID:27682823

Structure and Strength in Causal Induction

ERIC Educational Resources Information Center

Griffiths, Thomas L.; Tenenbaum, Joshua B.

2005-01-01

We present a framework for the rational analysis of elemental causal induction--learning about the existence of a relationship between a single cause and effect--based upon causal graphical models. This framework makes precise the distinction between causal structure and causal strength: the difference between asking whether a causal relationship…

Age-Dependent Glutamate Induction of Synaptic Plasticity in Cultured Hippocampal Neurons

ERIC Educational Resources Information Center

Ivenshitz, Miriam; Segal, Menahem; Sapoznik, Stav

2006-01-01

A common denominator for the induction of morphological and functional plasticity in cultured hippocampal neurons involves the activation of excitatory synapses. We now demonstrate massive morphological plasticity in mature cultured hippocampal neurons caused by a brief exposure to glutamate. This plasticity involves a slow, 70%-80% increase in…

Demonstration of Lenz's Law with an Induction Motor

ERIC Educational Resources Information Center

Kraftmakher, Yaakov

2005-01-01

The interaction of a conductor with a time-dependent magnetic field is an important topic of electromagnetic theory. A computerized classroom demonstration shows how the eddy currents induced in the rotor of an induction motor cause its rotation or braking. Both phenomena are directly related to Lenz's law.

Demonstration of LenzÂ's law with an induction motor

NASA Astrophysics Data System (ADS)

Kraftmakher, Yaakov

2005-03-01

The interaction of a conductor with a time-dependent magnetic field is an important topic of electromagnetic theory. A computerized classroom demonstration shows how the eddy currents induced in the rotor of an induction motor cause its rotation or braking. Both phenomena are directly related to Lenz’s law.

Repeated seizures induce long-term increase in hippocampal benzodiazepine receptors.

PubMed Central

McNamara, J O; Peper, A M; Patrone, V

1980-01-01

Repeated seizures, whether induced by kindling or electroshock, caused a long-lasting (at least 24 hr) increase of [3H]diazepam binding in hippocampal membranes of Sprague-Dawley rats. Scatchard analyses demonstrated that increased numbers of binding sites accounted for the increase. Neither repeated hypoxia nor repeated administration of electrical current without inducing seizures caused an increase of [3H]diazepam binding. Regardless of the method used for seizure induction, the response was graded in that large numbers of seizures were required to induce significant increases, whereas fewer seizures induced only slight increases. We suggest that the receptor increases imply a heightened response to benzodiazepines and more powerful hippocampal recurrent inhibition. PMID:6930682

Strain-dependent induction of epithelial cell oncosis by Campylobacter jejuni is correlated with invasion ability and is independent of cytolethal distending toxin.

PubMed

Kalischuk, Lisa D; Inglis, G Douglas; Buret, Andre G

2007-09-01

Induction of host cell death is thought to play an important role in bacterial pathogenesis. Campylobacter jejuni is a prevalent cause of bacterial enteritis; however, its effects on enterocytes remain unclear. The present study indicates for the first time that C. jejuni induces oncotic, rather than apoptotic death of T84 enterocytes. C. jejuni-treated enterocytes exhibited extensive cytoplasmic vacuolation, rapid (3-6 h) loss of plasma membrane integrity ('cytotoxicity'), loss of mitochondrial transmembrane potential, and ATP depletion. Enterocytes also exhibited increased oligonucleosomal DNA fragmentation, a feature characteristic of apoptosis. However, consistent with a non-apoptotic process, DNA fragmentation and cytotoxicity were not caspase dependent. During apoptosis, caspases mediate cleavage of poly(ADP-ribose) polymerase; however, cleavage was not observed in C. jejuni-treated monolayers. Cytotoxicity, ATP depletion and DNA fragmentation were not prevented by the deletion of the cytolethal distending toxin (CDT) gene, indicating that C. jejuni causes enterocyte oncosis via a mechanism that is CDT independent. The ability to cause oncosis was significantly decreased in a FlaAFlaB mutant (CDT(+)) that was defective in the ability to adhere and invade enterocytes. Analysis of clinical isolates revealed that oncosis was strain dependent and correlated with increased invasive ability. These observations offer new insights into the pathogenesis of C. jejuni infection.

Permissive role of the acidification caused by wheat aleurone layers upon. alpha. -amylase induction by GA sub 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez-Campos, E.; Bernal-Lugo, I.; Hamabata, A.

1989-04-01

Wheat aleurone has the capacity of acidifying the incubation medium in 1 to 2 pH units. The {alpha}-amylase induction by GA{sub 3} in isolated wheat aleurone layers is strongly dependent on acidic pH of the medium (pH < 5). To examine possible mechanisms {sup 35}-Met incorporation into proteins and {alpha}-amylase, in the presence of GA{sub 3} and Ca{sup 2+} at pH, 4, 5 and 6 was studied. Although {sup 35}-Met uptake decreased markedly ({approx} 90%) at pH 4 in thepresence of GA{sub 3}, incorporation into total protein did not change significantly from other conditions. Auto-radiography of SDS-PAGE showed that mostmore » of the amino acid was in the {alpha}-amylase band, meaning that the effect of acidic pH is specific for GA{sub 3} actions on aleurone tissue. On the other hand, an increase of protonated GA{sub 3} diffusion could be ruled out. Also, there was not {alpha}-amylase inactivation at pH 6. These findings point out to the important physiological role of the acidification caused by the aleurone.« less

Security region-based small signal stability analysis of power systems with FSIG based wind farm

NASA Astrophysics Data System (ADS)

Qin, Chao; Zeng, Yuan; Yang, Yang; Cui, Xiaodan; Xu, Xialing; Li, Yong

2018-02-01

Based on the Security Region approach, the impact of fixed-speed induction generator based wind farm on the small signal stability of power systems is analyzed. Firstly, the key factors of wind farm on the small signal stability of power systems are analyzed and the parameter space for small signal stability region is formed. Secondly, the small signal stability region of power systems with wind power is established. Thirdly, the corresponding relation between the boundary of SSSR and the dominant oscillation mode is further studied. Results show that the integration of fixed-speed induction generator based wind farm will cause the low frequency oscillation stability of the power system deteriorate. When the output of wind power is high, the oscillation stability of the power system is mainly concerned with the inter-area oscillation mode caused by the integration of the wind farm. Both the active power output and the capacity of reactive power compensation of the wind farm have a significant influence on the SSSR. To improve the oscillation stability of power systems with wind power, it is suggested to reasonably set the reactive power compensation capacity for the wind farm through SSSR.

Radon as a causative factor in induction of myeloid leukaemia and other cancers.

PubMed

Henshaw, D L; Eatough, J P; Richardson, R B

1990-04-28

The international incidence of myeloid leukaemia, cancer of the kidney, melanoma, and certain childhood cancers all show significant correlation with radon exposure in the home. For myeloid leukaemia, analysis suggests that in the UK 6-12% of incidence may be attributed to radon. In Cornwall, where radon levels are higher, the range is 23-43%. For the world average radon exposure of 50 Bq.m-3, 13-25% of myeloid leukaemia at all ages may be caused by radon.

Reduced epidermal thickness, nerve degeneration and increased pain-related behavior in rats with diabetes type 1 and 2.

PubMed

Boric, Matija; Skopljanac, Ivan; Ferhatovic, Lejla; Jelicic Kadic, Antonia; Banozic, Adriana; Puljak, Livia

2013-11-01

To examine the mechanisms contributing to pain genesis in diabetic neuropathy, we investigated epidermal thickness and number of intraepidermal nerve fibers in rat foot pad of the animal model of diabetes type 1 and type 2 in relation to pain-related behavior. Male Sprague-Dawley rats were used. Diabetes type 1 was induced with intraperitoneal injection of streptozotocin (STZ) and diabetes type 2 was induced with a combination of STZ and high-fat diet. Control group for diabetes type 1 was fed with regular laboratory chow, while control group for diabetes type 2 received high-fat diet. Body weights and blood glucose levels were monitored to confirm induction of diabetes. Pain-related behavior was analyzed using thermal (hot, cold) and mechanical stimuli (von Frey fibers, number of hyperalgesic responses). Two months after induction of diabetes, glabrous skin samples from plantar surface of the both hind paws were collected. Epidermal thickness was evaluated with hematoxylin and eosin staining. Intraepidermal nerve fibers quantification was performed after staining skin with polyclonal antiserum against protein gene product 9.5. We found that induction of diabetes type 1 and type 2 causes significant epidermal thinning and loss of intraepidermal nerve fibers in a rat model, and both changes were more pronounced in diabetes type 1 model. Significant increase of pain-related behavior two months after induction of diabetes was observed only in a model of diabetes type 1. In conclusion, animal models of diabetes type 1 and diabetes type 2 could be used in pharmacological studies, where cutaneous changes could be used as outcome measures for predegenerative markers of neuropathies. Copyright © 2013 Elsevier B.V. All rights reserved.

L-ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1.

PubMed

Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien; Lin, Chih-Hung; Lai, Chien-Cheng; Wang, Jia-Yi

2012-12-01

Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of l-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2',7'-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

P-glycoprotein induction in Caco-2 cells by newly synthetized thioxanthones prevents paraquat cytotoxicity.

PubMed

Silva, Renata; Palmeira, Andreia; Carmo, Helena; Barbosa, Daniel José; Gameiro, Mariline; Gomes, Ana; Paiva, Ana Mafalda; Sousa, Emília; Pinto, Madalena; Bastos, Maria de Lourdes; Remião, Fernando

2015-10-01

The induction of P-glycoprotein (P-gp), an ATP-dependent efflux pump, has been proposed as a strategy against the toxicity induced by P-gp substrates such as the herbicide paraquat (PQ). The aim of this study was to screen five newly synthetized thioxanthonic derivatives, a group known to interact with P-gp, as potential inducers of the pump's expression and/or activity and to evaluate whether they would afford protection against PQ-induced toxicity in Caco-2 cells. All five thioxanthones (20 µM) caused a significant increase in both P-gp expression and activity as evaluated by flow cytometry using the UIC2 antibody and rhodamine 123, respectively. Additionally, it was demonstrated that the tested compounds, when present only during the efflux of rhodamine 123, rapidly induced an activation of P-gp. The tested compounds also increased P-gp ATPase activity in MDR1-Sf9 membrane vesicles, indicating that all derivatives acted as P-gp substrates. PQ cytotoxicity was significantly reduced in the presence of four thioxanthone derivatives, and this protective effect was reversed upon incubation with a specific P-gp inhibitor. In silico studies showed that all the tested thioxanthones fitted onto a previously described three-feature P-gp induction pharmacophore. Moreover, in silico interactions between thioxanthones and P-gp in the presence of PQ suggested that a co-transport mechanism may be operating. Based on the in vitro activation results, a pharmacophore model for P-gp activation was built, which will be of further use in the screening for new P-gp activators. In conclusion, the study demonstrated the potential of the tested thioxanthonic compounds in protecting against toxic effects induced by P-gp substrates through P-gp induction and activation.

Chemopreventive Activity of MGN-3/Biobran Against Chemical Induction of Glandular Stomach Carcinogenesis in Rats and Its Apoptotic Effect in Gastric Cancer Cells.

PubMed

Badr El-Din, Nariman K; Abdel Fattah, Salma M; Pan, Deyu; Tolentino, Lucilene; Ghoneum, Mamdooh

2016-12-01

In the current study, we investigated the chemopreventive activity of arabinoxylan rice bran, MGN-3/Biobran, against chemical induction of glandular stomach carcinogenesis in rats. Gastric cancer was induced by carcinogen methylnitronitrosoguanidine (MNNG), and rats received MNNG alone or MNNG plus Biobran (40 mg/kg body weight) for a total of 8 months. Averaged results from 2 separate readings showed that exposure to MNNG plus Biobran caused gastric dysplasia and cancer (adenocarcinoma) in 4.5/12 rats (9/24 readings, 37.5%), with 3.5/12 rats (7/24 readings, 29.2%) showing dysplasia and 1/12 rats (8.3%) developing adenocarcinoma. In contrast, in rats treated with MNNG alone, 8/10 (80%) developed dysplasia and adenocarcinoma, with 6/10 rats (60%) showing dysplasia and 2/10 rats (20%) developing adenocarcinoma. The effect of combining both agents was also associated with significant suppression of the expression of the tumor marker Ki-67 and remarkable induction in the apoptotic gastric cancer cells via mitochondrial-dependent pathway as indicated by the upregulation in p53 expression, Bax expression, downregulation in Bcl-2 expression, an increase in Bax/Bcl-2 ratio, and an activation of caspase-3. In addition, Biobran treatment induced cell-cycle arrest in the subG1 phase, where the hypodiploid cell population was markedly increased. Moreover, Biobran treatment protected rats against MNNG-induced significant decrease in lymphocyte levels. We conclude that Biobran provides protection against chemical induction of glandular stomach carcinogenesis in rats and may be useful for the treatment of human patients with gastric cancer. © The Author(s) 2016.

Mechanically induced c-fos expression is mediated by cAMP in MC3T3-E1 osteoblasts

NASA Technical Reports Server (NTRS)

Fitzgerald, J.; Hughes-Fulford, M.

1999-01-01

In serum-deprived MC3T3-E1 osteoblasts, mechanical stimulation caused by mild (287 x g) centrifugation induced a 10-fold increase in mRNA levels of the proto-oncogene, c-fos. Induction of c-fos was abolished by the cAMP-dependent protein kinase inhibitor H-89, suggesting that the transient c-fos mRNA increase is mediated by cAMP. Down-regulation of protein kinase C (PKC) activity by chronic TPA treatment failed to significantly reduce c-fos induction, suggesting that TPA-sensitive isoforms of PKC are not responsible for c-fos up-regulation. In addition, 287 x g centrifugation increased intracellular prostaglandin E2 (PGE2) levels 2.8-fold (P<0. 005). Since we have previously shown that prostaglandin E2 (PGE2) can induce c-fos expression via a cAMP-mediated mechanism, we asked whether the increase in c-fos mRNA was due to centrifugation-induced PGE2 release. Pretreatment with the cyclooxygenase inhibitors indomethacin and flurbiprofen did not hinder the early induction of c-fos by mechanical stimulation. We conclude that c-fos expression induced by mild mechanical loading is dependent primarily on cAMP, not PKC, and initial induction of c-fos is not necessarily dependent on the action of newly synthesized PGE2.

Haplodeficiency of Klotho Gene Causes Arterial Stiffening via Upregulation of Scleraxis Expression and Induction of Autophagy.

PubMed

Chen, Kai; Zhou, Xiaoli; Sun, Zhongjie

2015-11-01

The prevalence of arterial stiffness increases with age, whereas the level of the aging-suppressor protein klotho decreases with age. The objective of this study is to assess whether haplodeficiency of klotho gene causes arterial stiffness and to investigate the underlying mechanism. Pulse wave velocity, a direct measure of arterial stiffness, was increased significantly in klotho heterozygous (klotho(+/-)) mice versus their age-matched wild-type (WT) littermates, suggesting that haplodeficiency of klotho causes arterial stiffening. Notably, plasma aldosterone levels were elevated significantly in klotho(+/-) mice. Treatment with eplerenone (6 mg/kg per day IP), an aldosterone receptor blocker, abolished klotho deficiency-induced arterial stiffening in klotho(+/-) mice. Klotho deficiency was associated with increased collagen and decreased elastin contents in the media of aortas. In addition, arterial matrix metalloproteinase-2, matrix metalloproteinase-9, and transforming growth factor-β1 expression and myofibroblast differentiation were increased in klotho(+/-) mice. These klotho deficiency-related changes can be blocked by eplerenone. Protein expression of scleraxis, a transcription factor for collagen synthesis, and LC3-II/LC3-I, an index of autophagy, were upregulated in aortas of klotho(+/-) mice, which can be abolished by eplerenone. In cultured mouse aortic smooth muscle cells, aldosterone increased collagen-1 expression that can be completely eliminated by small interfering RNA knockdown of scleraxis. Interestingly, aldosterone decreased elastin levels in smooth muscle cells, which can be abolished by small interfering RNA knockdown of Beclin-1, an autophagy-related gene. In conclusion, this study demonstrated for the first time that klotho deficiency-induced arterial stiffening may involve aldosterone-mediated upregulation of scleraxis and induction of autophagy, which led to increased collagen-1 expression and decreased elastin levels, respectively. © 2015 American Heart Association, Inc.

The influence of gemfibrozil on malondialdehyde level and paraoxonase 1 activity in wistar and fisher rats.

PubMed

Macan, Marija; Marija, Macan; Konjevoda, Paško; Paško, Konjevoda; Lovric, Jasna; Jasna, Lovrić; Koprivanac, Marijan; Marijan, Koprivanac; Kelava, Marta; Marta, Kelava; Vrkic, Nada; Nada, Vrkić; Bradamante, Vlasta; Vlasta, Bradamante

2011-06-01

There are diverse experimental data about the influence of gemfibrozil (GEM) on the production of hydrogen peroxide (H(2)O(2)) and antioxidant enzymes. We investigated the influence of GEM treatment on the production of malondialdehyde (MDA) level in tissues of normolipidaemic Wistar and Fisher rats which is an index of lipid peroxidation. Because serum paraoxonase 1 (PON1) is an important enzyme with specific protective function on metabolism of lipid peroxides, we examined the influence of GEM on PON1 activity in liver and serum. MDA level and enzyme activities were also determined 10 days after withdrawal of GEM treatment. The significantly increased levels of MDA in liver, kidney and heart of both rat strains were obtained after 3 weeks of GEM treatment. We propose two possibilities for the increase of MDA levels caused by GEM, induction of peroxisome proliferation and activities of enzymes that participated in occurrence of H(2)O(2) and possible reduction of enzyme activities including in H(2)O(2) metabolism. Ten days after withdrawal of GEM treatment, MDA levels in all tissue levels of both rat strains were less in comparison with GEM treatment. GEM caused a significant drop of PON1 activity in serum and liver of Fisher rats, and in liver of Wistar rats. We suggest that GEM, through induction of lipid peroxidation, caused the damage of hepatocytes with consequent reduction of PON1 synthesis. The increase in PON1 activity in serum and tissues of both rat strains 10 days after withdrawal of GEM treatment shows the fast recovery of enzyme synthesis. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Prolonged Neutrophil Dysfunction Following Plasmodium falciparum Malaria is Related to Hemolysis and Heme Oxygenase-1 Induction1

PubMed Central

Cunnington, Aubrey J.; Njie, Madi; Correa, Simon; Takem, Ebako N.; Riley, Eleanor M.; Walther, Michael

2012-01-01

It is not known why people are more susceptible to bacterial infections such as non-Typhoid Salmonella (NTS) during and after a malaria infection but, in mice, malarial hemolysis impairs resistance to NTS by impairing the neutrophil oxidative burst. This acquired neutrophil dysfunction is a consequence of induction of the cytoprotective, heme degrading enzyme heme oxygenase-1 (HO-1) in neutrophil progenitors in bone marrow. In this study, we assessed whether neutrophil dysfunction occurs in humans with malaria and how this relates to hemolysis. We evaluated neutrophil function in 58 Gambian children with Plasmodium falciparum malaria (55 (95%) with uncomplicated disease), and examined associations with erythrocyte count, haptoglobin, hemopexin, plasma heme, expression of receptors for heme uptake, and HO-1 induction. Malaria caused the appearance of a dominant population of neutrophils with reduced oxidative burst activity, which gradually normalized over 8 weeks of follow-up. The degree of neutrophil impairment correlated significantly with markers of hemolysis and HO-1 induction. HO-1 expression was increased in blood during acute malaria, but at a cellular level HO-1 expression was modulated by changes in surface expression of the haptoglobin receptor (CD163). These findings demonstrate that neutrophil dysfunction occurs in P. falciparum malaria and support the relevance of the mechanistic studies in mice. Furthermore, they suggest the presence of a regulatory pathway to limit HO-1 induction by hemolysis in the context of infection, and indicate new targets for therapeutic intervention to abrogate the susceptibility to bacterial infection in the context of hemolysis in humans. PMID:23100518

Comparison of efficacy and toxicity of doxorubicin and mitoxantrone in combination chemotherapy for canine lymphoma

PubMed Central

Wang, Shang-Lin; Lee, Jih-Jong; Liao, Albert Taiching

2016-01-01

Forty-four dogs with multicentric lymphoma were treated using a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) induction protocol or treated using a cyclophosphamide, mitoxantrone, vincristine, and prednisolone (CMOP) induction protocol. There was no statistical difference in signalment and the presence of historical negative prognostic factors between the groups. The median progression-free survival (PFS) in the CHOP and CMOP groups were 222 d and 162 d, respectively (P = 0.75). The median survival time (MST) of dogs in CHOP and CMOP groups were 318 d and 242 d, respectively (P = 0.63). Anorexia and diarrhea episodes were significantly higher in the CHOP group than in the CMOP group (P = 0.02 and P = 0.01, respectively). These results suggest that the CMOP protocol provides similar PFS, MST and causes fewer side effects compared to the CHOP protocol. Therefore, the CMOP protocol may be another treatment choice for canine multicentric lymphoma. PMID:26933263

Comparison of efficacy and toxicity of doxorubicin and mitoxantrone in combination chemotherapy for canine lymphoma.

PubMed

Wang, Shang-Lin; Lee, Jih-Jong; Liao, Albert Taiching

2016-03-01

Forty-four dogs with multicentric lymphoma were treated using a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) induction protocol or treated using a cyclophosphamide, mitoxantrone, vincristine, and prednisolone (CMOP) induction protocol. There was no statistical difference in signalment and the presence of historical negative prognostic factors between the groups. The median progression-free survival (PFS) in the CHOP and CMOP groups were 222 d and 162 d, respectively (P = 0.75). The median survival time (MST) of dogs in CHOP and CMOP groups were 318 d and 242 d, respectively (P = 0.63). Anorexia and diarrhea episodes were significantly higher in the CHOP group than in the CMOP group (P = 0.02 and P = 0.01, respectively). These results suggest that the CMOP protocol provides similar PFS, MST and causes fewer side effects compared to the CHOP protocol. Therefore, the CMOP protocol may be another treatment choice for canine multicentric lymphoma.

Face to face with emotion: holistic face processing is modulated by emotional state.

PubMed

Curby, Kim M; Johnson, Kareem J; Tyson, Alyssa

2012-01-01

Negative emotions are linked with a local, rather than global, visual processing style, which may preferentially facilitate feature-based, relative to holistic, processing mechanisms. Because faces are typically processed holistically, and because social contexts are prime elicitors of emotions, we examined whether negative emotions decrease holistic processing of faces. We induced positive, negative, or neutral emotions via film clips and measured holistic processing before and after the induction: participants made judgements about cued parts of chimeric faces, and holistic processing was indexed by the interference caused by task-irrelevant face parts. Emotional state significantly modulated face-processing style, with the negative emotion induction leading to decreased holistic processing. Furthermore, self-reported change in emotional state correlated with changes in holistic processing. These results contrast with general assumptions that holistic processing of faces is automatic and immune to outside influences, and they illustrate emotion's power to modulate socially relevant aspects of visual perception.

Benzo[a]pyrene-7,8-dihydrodiol promotes checkpoint activation and G2/M arrest in human bronchoalveolar carcinoma H358 cells.

PubMed

Caino, M Cecilia; Oliva, Jose L; Jiang, Hao; Penning, Trevor M; Kazanietz, Marcelo G

2007-03-01

Polycyclic aromatic hydrocarbons (PAHs) are potent carcinogens that require metabolic activation inside cells. The proximate carcinogens PAH-diols can be converted to o-quinones by aldo-keto reductases (AKRs) or to diol-epoxides by cytochrome P450 (P450) enzymes. We assessed the effect of benzo[a]pyrene-7,8-dihydrodiol (BPD) on proliferation in p53-null bronchoalveolar carcinoma H358 cells. BPD treatment led to a significant inhibition of proliferation and arrest in G2/M in H358 cells. The relative contribution of the AKR and P450 pathways to cell cycle arrest was assessed. Overexpression of AKR1A1 did not affect cell proliferation or cell cycle progression, and benzo[a]pyrene-7,8-dione did not cause any noticeable effect on cell growth, suggesting that AKR1A1 metabolic products were not involved in the antiproliferative effect of BPD. On the other hand, blockade of P450 induction or inhibition of P450 activity greatly impaired the effect of BPD. Moreover, P450 induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin significantly enhanced the antiproliferative effect of BPD. Mechanistic studies revealed that BPD caused a DNA damage response, Chk1 activation, and accumulation of phospho-Cdc2 (Tyr15) in H358 cells, effects that were impaired by an ataxia-telangectasia mutated (ATM)/ATM-related (ATR) inhibitor. Similar results were observed in human bronchoepithelial BEAS-2B cells, arguing for analogous mechanisms in tumorigenic and immortalized nontumorigenic cells lacking functional p53. Our data suggest that a p53-independent pathway operates in lung epithelial cells in response to BPD that involves P450 induction and subsequent activation of the ATR/ATM/Chk1 damage check-point pathway and cell cycle arrest in G2/M.

Retinal ischemic injury rescued by sodium 4-phenylbutyrate in a rat model.

PubMed

Jeng, Yung-Yue; Lin, Nien-Ting; Chang, Pen-Heng; Huang, Yuan-Ping; Pang, Victor Fei; Liu, Chen-Hsuan; Lin, Chung-Tien

2007-03-01

Retinal ischemia is a common cause of visual impairment for humans and animals. Herein, the neuroprotective effects of phenylbutyrate (PBA) upon retinal ischemic injury were investigated using a rat model. Retinal ganglion cells (RGCs) were retrograde labeled with the fluorescent tracer fluorogold (FG) applied to the superior collicoli of test Sprague-Dawley rats. High intraocular pressure and retinal ischemia were induced seven days subsequent to such FG labeling. A dose of either 100 or 400 mg/kg PBA was administered intraperitoneally to test rats at two time points, namely 30 min prior to the induction of retinal ischemia and 1 h subsequent to the cessation of the procedure inducing retinal ischemia. The test-rat retinas were collected seven days subsequent to the induction of retinal ischemia, and densities of surviving RGCs were estimated by counting FG-labeled RGCs within the retina. Histological analysis revealed that ischemic injury caused the loss of retinal RGCs and a net decrease in retinal thickness. For PBA-treated groups, almost 100% of the RGCs were preserved by a pre-ischemia treatment with PBA (at a dose of either 100 or 400 mg/kg), while post-ischemia treatment of RGCs with PBA did not lead to the preservation of RGCs from ischemic injury by PBA as determined by the counting of whole-mount retinas. Pre-ischemia treatment of RGCs with PBA (at a dose of either 100 or 400 mg/kg) significantly reduced the level of ischemia-associated loss of thickness of the total retina, especially the inner retina, and the inner plexiform layer of retina. Besides, PBA treatment significantly reduced the ischemia-induced loss of cells in the ganglion-cell layer of the retina. Taken together, these results suggest that PBA demonstrates a marked neuroprotective effect upon high intraocular pressure-induced retinal ischemia when the PBA is administered prior to ischemia induction.

Matrix metalloproteinase-3 causes dopaminergic neuronal death through Nox1-regenerated oxidative stress.

PubMed

Choi, Dong-Hee; Kim, Ji-Hye; Seo, Joo-Ha; Lee, Jongmin; Choi, Wahn Soo; Kim, Yoon-Seong

2014-01-01

In the present study we investigated the interplay between matrix metalloproteinase 3 (MMP3) and NADPH oxidase 1 (Nox1) in the process of dopamine (DA) neuronal death. We found that MMP3 activation causes the induction of Nox1 via mitochondrial reactive oxygen species (ROS) production and subsequently Rac1 activation, eventually leading to Nox1-derived superoxide generation in a rat DA neuronal N27 cells exposed to 6-OHDA. While a MMP3 inhibitor, NNGH, largely attenuated mitochondrial ROS and subsequent Nox1 induction, both apocynin, a putative Nox inhibitor and GKT137831, a Nox1 selective inhibitor failed to reduce 6-OHDA-induced mitochondrial ROS. However, both inhibitors for MMP3 and Nox1 similarly attenuated 6-OHDA-induced N27 cell death. RNAi-mediated selective inhibition of MMP3 or Nox1 showed that knockdown of either MMP3 or Nox1 significantly reduced 6-OHDA-induced ROS generation in N27 cells. While 6-OHDA-induced Nox1 was abolished by MMP3 knockdown, Nox1 knockdown did not alter MMP3 expression. Direct overexpression of autoactivated MMP3 (actMMP3) in N27 cells or in rat substantia nigra (SN) increased expression of Nox1. Selective knockdown of Nox1 in the SN achieved by adeno-associated virus-mediated overexpression of Nox1-specific shRNA largely attenuated the actMMP3-mediated dopaminergic neuronal loss. Furthermore, Nox1 expression was significantly attenuated in Mmp3 null mice treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Together we established novel molecular mechanisms underlying oxidative stress-mediated dopaminergic neuronal death in which MMP3 activation is a key upstream event that leads to mitochondrial ROS, Nox1 induction and eventual dopaminergic neuronal death. Our findings may lead to the development of novel therapeutic approach.

Effect of different methods of pulse width modulation on power losses in an induction motor

NASA Astrophysics Data System (ADS)

Gulyaev, Alexander; Fokin, Dmitrii; Shuharev, Sergey; Ten, Evgenii

2017-10-01

We consider the calculation of modulation power losses in a system “induction motor-inverter” for various pulse width modulation (PWM) methods of the supply voltage. Presented values of modulation power losses are the result of modeling a system “DC link - two-level three-phase voltage inverter - induction motor - load”. In this study the power losses in a system “induction motor - inverter” are computed, as well as losses caused by higher harmonics of PWM supply voltage, followed by definition of active power consumed by the DC link for a specified value mechanical power on the induction motor shaft. Mechanical power was determined by the rotation speed and the torque on the motor shaft in various quasi-sinusoidal supply voltage PWM modes. These calculations reveal the best coefficient of performance (COP) in a system of a variable frequency drive (VFD) with independent voltage inverter controlled by induction motor PWM.

Prophage Induction Is Enhanced and Required for Renal Disease and Lethality in an EHEC Mouse Model

PubMed Central

Reynolds, Jared L.; Alteri, Christopher J.; Skinner, Katherine G.; Friedman, Jonathan H.; Eaton, Kathryn A.; Friedman, David I.

2013-01-01

Enterohemorrhagic Escherichia coli (EHEC), particularly serotype O157:H7, causes hemorrhagic colitis, hemolytic uremic syndrome, and even death. In vitro studies showed that Shiga toxin 2 (Stx2), the primary virulence factor expressed by EDL933 (an O157:H7 strain), is encoded by the 933W prophage. And the bacterial subpopulation in which the 933W prophage is induced is the producer of Stx2. Using the germ-free mouse, we show the essential role 933W induction plays in the virulence of EDL933 infection. An EDL933 derivative with a single mutation in its 933W prophage, resulting specifically in that phage being uninducible, colonizes the intestines, but fails to cause any of the pathological changes seen with the parent strain. Hence, induction of the 933W prophage is the primary event leading to disease from EDL933 infection. We constructed a derivative of EDL933, SIVET, with a biosensor that specifically measures induction of the 933W prophage. Using this biosensor to measure 933W induction in germ-free mice, we found an increase three logs greater than was expected from in vitro results. Since the induced population produces and releases Stx2, this result indicates that an activity in the intestine increases Stx2 production. PMID:23555250

Lipid-Emulsion Propofol Less Attenuates the Regulation of Body Temperature than Micro-Emulsion Propofol or Sevoflurane in the Elderly

PubMed Central

Jeong, Cheol Won; Ju, Jin; Lee, Dae Wook; Lee, Seong Heon

2012-01-01

Purpose Anesthesia and surgery commonly cause hypothermia, and this caused by a combination of anesthetic-induced impairment of thermoregulatory control, a cold operation room environment and other factors that promote heat loss. All the general anesthetics markedly impair normal autonomic thermoregulatory control. The aim of this study is to evaluate the effect of two different types of propofol versus inhalation anesthetic on the body temperature. Materials and Methods In this randomized controlled study, 36 patients scheduled for elective laparoscopic gastrectomy were allocated into three groups; group S (sevoflurane, n=12), group L (lipid-emulsion propofol, n=12) and group M (micro-emulsion propofol, n=12). Anesthesia was maintained with typical doses of the study drugs and all the groups received continuous remifentanil infusion. The body temperature was continuously monitored after the induction of general anesthesia until the end of surgery. Results The body temperature was decreased in all the groups. The temperature gradient of each group (group S, group L and group M) at 180 minutes from induction of anesthesia was 2.5±0.6℃, 1.6±0.5℃ and 2.3±0.6℃, respectively. The body temperature of group L was significantly higher than that of group S and group M at 30 minutes and 75 minute after induction of anesthesia, respectively. There were no temperature differences between group S and group M. Conclusion The body temperature is maintained at a higher level in elderly patients anesthetized with lipid-emulsion propofol. PMID:22187253

Lipid-emulsion propofol less attenuates the regulation of body temperature than micro-emulsion propofol or sevoflurane in the elderly.

PubMed

Jeong, Cheol Won; Ju, Jin; Lee, Dae Wook; Lee, Seong Heon; Yoon, Myung Ha

2012-01-01

Anesthesia and surgery commonly cause hypothermia, and this caused by a combination of anesthetic-induced impairment of thermoregulatory control, a cold operation room environment and other factors that promote heat loss. All the general anesthetics markedly impair normal autonomic thermoregulatory control. The aim of this study is to evaluate the effect of two different types of propofol versus inhalation anesthetic on the body temperature. In this randomized controlled study, 36 patients scheduled for elective laparoscopic gastrectomy were allocated into three groups; group S (sevoflurane, n=12), group L (lipid-emulsion propofol, n=12) and group M (micro-emulsion propofol, n=12). Anesthesia was maintained with typical doses of the study drugs and all the groups received continuous remifentanil infusion. The body temperature was continuously monitored after the induction of general anesthesia until the end of surgery. The body temperature was decreased in all the groups. The temperature gradient of each group (group S, group L and group M) at 180 minutes from induction of anesthesia was 2.5 ± 0.6°C, 1.6 ± 0.5°C and 2.3 ± 0.6°C, respectively. The body temperature of group L was significantly higher than that of group S and group M at 30 minutes and 75 minute after induction of anesthesia, respectively. There were no temperature differences between group S and group M. The body temperature is maintained at a higher level in elderly patients anesthetized with lipid-emulsion propofol.

Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles.

PubMed

Gandini, Mariana; Reis, Sonia Regina Nogueira Ignacio; Torrentes-Carvalho, Amanda; Azeredo, Elzinandes Leal; Freire, Marcos da Silva; Galler, Ricardo; Kubelka, Claire Fernandes

2011-08-01

Flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. Dendritic cells (DCs) are targets for dengue virus (DENV) and yellow fever virus (YF) replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. We studied the infectivity of DENV2 (strain 16681), a YF vaccine (YF17DD) and a chimeric YF17D/DENV2 vaccine in monocyte-derived DCs in vitro with regard to cell maturation, activation and cytokine production. Higher viral antigen positive cell frequencies were observed for DENV2 when compared with both vaccine viruses. Flavivirus-infected cultures exhibited dendritic cell activation and maturation molecules. CD38 expression on DCs was enhanced for both DENV2 and YF17DD, whereas OX40L expression was decreased as compared to mock-stimulated cells, suggesting that a T helper 1 profile is favoured. Tumor necrosis factor (TNF)-α production in cell cultures was significantly higher in DENV2-infected cultures than in cultures infected with YF17DD or YF17D/DENV. In contrast, the vaccines induced higher IFN-α levels than DENV2. The differential cytokine production indicates that DENV2 results in TNF induction, which discriminates it from vaccine viruses that preferentially stimulate interferon expression. These differential response profiles may influence the pathogenic infection outcome.

First sickle cell crisis triggered by induction of labor in a primigravida.

PubMed

Faron, G; Corbisier, C; Tecco, L; Vokaer, A

2001-02-01

Sickle cell anemia is a severe disorder that rarely spares affected adults. We describe here a 32-year-old pregnant woman who presented her first lifetime symptoms of her disease during induction of labor at term. We therefore discuss the possible causes that may have triggered this inaugural crisis.

Dependency of Calcium Alternans on Ryanodine Receptor Refractoriness

PubMed Central

Alvarez-Lacalle, Enric; Cantalapiedra, Inma R.; Peñaranda, Angelina; Cinca, Juan; Hove-Madsen, Leif; Echebarria, Blas

2013-01-01

Background Rapid pacing rates induce alternations in the cytosolic calcium concentration caused by fluctuations in calcium released from the sarcoplasmic reticulum (SR). However, the relationship between calcium alternans and refractoriness of the SR calcium release channel (RyR2) remains elusive. Methodology/Principal Findings To investigate how ryanodine receptor (RyR2) refractoriness modulates calcium handling on a beat-to-beat basis using a numerical rabbit cardiomyocyte model. We used a mathematical rabbit cardiomyocyte model to study the beat-to-beat calcium response as a function of RyR2 activation and inactivation. Bi-dimensional maps were constructed depicting the beat-to-beat response. When alternans was observed, a novel numerical clamping protocol was used to determine whether alternans was caused by oscillations in SR calcium loading or by RyR2 refractoriness. Using this protocol, we identified regions of RyR2 gating parameters where SR calcium loading or RyR2 refractoriness underlie the induction of calcium alternans, and we found that at the onset of alternans both mechanisms contribute. At low inactivation rates of the RyR2, calcium alternans was caused by alternation in SR calcium loading, while at low activation rates it was caused by alternation in the level of available RyR2s. Conclusions/Significance We have mapped cardiomyocyte beat-to-beat responses as a function of RyR2 activation and inactivation, identifying domains where SR calcium load or RyR2 refractoriness underlie the induction of calcium alternans. A corollary of this work is that RyR2 refractoriness due to slow recovery from inactivation can be the cause of calcium alternans even when alternation in SR calcium load is present. PMID:23390511

Diffusion-mediated dephasing in the dipole field around a single spherical magnetic object.

PubMed

Buschle, Lukas R; Kurz, Felix T; Kampf, Thomas; Triphan, Simon M F; Schlemmer, Heinz-Peter; Ziener, Christian Herbert

2015-11-01

In this work, the time evolution of the free induction decay caused by the local dipole field of a spherical magnetic perturber is analyzed. The complicated treatment of the diffusion process is replaced by the strong-collision-approximation that allows a determination of the free induction decay in dependence of the underlying microscopic tissue parameters such as diffusion coefficient, sphere radius and susceptibility difference. The interplay between susceptibility- and diffusion-mediated effects yields several dephasing regimes of which, so far, only the classical regimes of motional narrowing and static dephasing for dominant and negligible diffusion, respectively, were extensively examined. Due to the asymmetric form of the dipole field for spherical objects, the free induction decay exhibits a complex component in contradiction to the cylindrical case, where the symmetric local dipole field only causes a purely real induction decay. Knowledge of the shape of the corresponding frequency distribution is necessary for the evaluation of more sophisticated pulse sequences and a detailed understanding of the off-resonance distribution allows improved quantification of transverse relaxation. Copyright © 2015 Elsevier Inc. All rights reserved.

Uncoupling thermotolerance from the induction of heat shock proteins.

PubMed Central

Smith, B J; Yaffe, M P

1991-01-01

Exposure of cells to elevated temperatures causes a rapid increase in the synthesis of heat shock proteins (hsps) and induces thermotolerance, the increased ability of cells to survive exposure to lethal temperatures; however, the connection between hsp induction and the acquisition of thermotolerance is unclear. hsp induction in the yeast Saccharomyces cerevisiae is mediated by the activation of heat-shock transcription factor, and recently we have described a mutation, hsf1-m3, in heat-shock transcription factor that prevents the factor's activation. We now demonstrate that this mutation results in a general block in heat-shock induction but does not affect the acquisition of thermotolerance. Our results indicate that high-level induction of the major hsps is not required for cells to acquire thermotolerance. Images PMID:1763024

Inductive phenomena at low frequencies in impedance spectra of proton exchange membrane fuel cells - A review

NASA Astrophysics Data System (ADS)

Pivac, Ivan; Barbir, Frano

2016-09-01

The results of electrochemical impedance spectroscopy of proton exchange membrane (PEM) fuel cells may exhibit inductive phenomena at low frequencies. The occurrence of inductive features at high frequencies is explained by the cables and wires of the test system. However, explanation of inductive loop at low frequencies requires a more detailed study. This review paper discusses several possible causes of such inductive behavior in PEM fuel cells, such as side reactions with intermediate species, carbon monoxide poisoning, and water transport, also as their equivalent circuit representations. It may be concluded that interpretation of impedance spectra at low frequencies is still ambiguous, and that better equivalent circuit models are needed with clearly defined physical meaning of each of the circuit elements.

Increase in the Acceleration Efficiency of Solids in a Hybrid Coaxial Magnetoplasma Accelerator

NASA Astrophysics Data System (ADS)

Gerasimov, D. Yu.; Sivkov, A. A.

2018-01-01

It is shown that in a hybrid coaxial magnetoplasma accelerator with a channel length of 350 mm and a diameter of 23 mm, the acceleration velocity and the energy conversion efficiency increase as the length of the plasma structure formation channel filled with a gas-generating material decreases from 17 to 9 mm. It is found that it is reasonable to use paraffin as the gas-generating material as it has a less significant deionizing effect on the high-current arc discharge and hence causes a less significant decrease in the discharge current intensity and an increase in conductive and inductive electrodynamic forces.

Endosulfan and cholinergic (muscarinic) transmission: effect on electroencephalograms and (/sup 3/H)quinuclidinyl benzilate in pigeon brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anand, M.; Agrawal, A.K.; Gopal, K.

Single exposure of endosulfan (5 mg/kg) to pigeons (Columbia livia) caused neuronal hyperexcitability as evidence by spike discharges of 200-500 ..mu..V in the electroencephalograms (EEG) from the telencephalon and hyperstriatum, but there was not effect on the ectostriatal area. Cholinergic (muscarinic) receptor binding study using (/sup 3/H)quinuclidinyl benzilate ((/sup 3/H)QNB) as a specific ligand indicated that a single exposure to 5 mg/kg of endosulfan caused a significant increase in (/sup 3/H)QNB binding to the striatal membrane. Behavior study further indicated that a single dose of 200 ..mu..g/kg of oxotremorine produced a significant induction in the tremor in endosulfan-pretreated pigeons. Themore » results of this behavioral and biochemical study indicate the involvement of a cholinergic (muscarinic) transmitter system in endosulfan-induced neurotoxicity.« less

Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma.

PubMed

Ahmad, Munirah; Suhaimi, Shazlan-Noor; Chu, Tai-Lin; Abdul Aziz, Norazlin; Mohd Kornain, Noor-Kaslina; Samiulla, D S; Lo, Kwok-Wai; Ng, Chew-Hee; Khoo, Alan Soo-Beng

2018-01-01

Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity.

Welding quality evaluation of resistance spot welding using the time-varying inductive reactance signal

NASA Astrophysics Data System (ADS)

Zhang, Hongjie; Hou, Yanyan; Yang, Tao; Zhang, Qian; Zhao, Jian

2018-05-01

In the spot welding process, a high alternating current is applied, resulting in a time-varying electromagnetic field surrounding the welder. When measuring the welding voltage signal, the impedance of the measuring circuit consists of two parts: dynamic resistance relating to weld nugget nucleation event and inductive reactance caused by mutual inductance. The aim of this study is to develop a method to acquire the dynamic reactance signal and to discuss the possibility of using this signal to evaluate the weld quality. For this purpose, a series of experiments were carried out. The reactance signals under different welding conditions were compared and the results showed that the morphological feature of the reactance signal was closely related to the welding current and it was also significantly influenced by some abnormal welding conditions. Some features were extracted from the reactance signal and combined to construct weld nugget strength and diameter prediction models based on the radial basis function (RBF) neural network. In addition, several features were also used to monitor the expulsion in the welding process by using Fisher linear discriminant analysis. The results indicated that using the dynamic reactance signal to evaluate weld quality is possible and feasible.

Reduction of magnetic field fluctuations in powered magnets for NMR using inductive measurements and sampled-data feedback control.

PubMed

Li, Mingzhou; Schiano, Jeffrey L; Samra, Jenna E; Shetty, Kiran K; Brey, William W

2011-10-01

Resistive and hybrid (resistive/superconducting) magnets provide substantially higher magnetic fields than those available in low-temperature superconducting magnets, but their relatively low spatial homogeneity and temporal field fluctuations are unacceptable for high resolution NMR. While several techniques for reducing temporal fluctuations have demonstrated varying degrees of success, this paper restricts attention to methods that utilize inductive measurements and feedback control to actively cancel the temporal fluctuations. In comparison to earlier studies using analog proportional control, this paper shows that shaping the controller frequency response results in significantly higher reductions in temporal fluctuations. Measurements of temporal fluctuation spectra and the frequency response of the instrumentation that cancels the temporal fluctuations guide the controller design. In particular, we describe a sampled-data phase-lead-lag controller that utilizes the internal model principle to selectively attenuate magnetic field fluctuations caused by the power supply ripple. We present a quantitative comparison of the attenuation in temporal fluctuations afforded by the new design and a proportional control design. Metrics for comparison include measurements of the temporal fluctuations using Faraday induction and observations of the effect that the fluctuations have on nuclear resonance measurements. Copyright © 2011. Published by Elsevier Inc.

The effects of pilocarpine nitrate upon the mitotic index of mouse bone marrow cells.

PubMed

Prabhu, M P; Hegde, M J

1991-11-01

Aneuploidies are the most common chromosomal causes for spontaneous abortions and constitute a major part of genetic disorders among the neonates. Aneuploidy producing agents (aneugens) pose serious genetic hazards to the human population. Therefore, testing for aneuploidy induction should be part of the requirement in drug safety guidelines. The aneugenic potential of pilocarpine nitrate, an alkaloid drug used as an ophthalmic solution was screened by chromosome analysis studies in the bone marrow cells of mice. Using the technique developed by Miller and Adler (1989) we evaluated changes in the mitotic index (MI), induction of chromatid contraction and spreading (C-mitoses) and decrease of anaphase frequencies as indicators of the aneuploidy inducing potency of the drug. Concentrations of pilocarpine nitrate of 4, 8 and 12 mg/kg body weight were administered intraperitoneally to mice. Colchicine-treated and water-treated animals formed the positive and negative controls. The data obtained in the cytogenetic analysis of both dose-response and time-response studies showed a significant induction of C-mitotic effects in the mouse bone marrow. The positive results indicated that the drug is a potential aneugen and should be further evaluated.

Sterilization of beehive material with a double inductively coupled low pressure plasma

NASA Astrophysics Data System (ADS)

Priehn, M.; Denis, B.; Aumeier, P.; Kirchner, W. H.; Awakowicz, P.; Leichert, L. I.

2016-09-01

American Foulbrood is a severe, notifiable disease of the honey bee. It is caused by infection of bee larvae with spores of the gram-positive bacterium Paenibacillus larvae. Spores of this organism are found in high numbers in an infected hive and are highly resistant to physical and chemical inactivation methods. The procedures to rehabilitate affected apiaries often result in the destruction of beehive material. In this study we assess the suitability of a double inductively coupled low pressure plasma as a non-destructive, yet effective alternative inactivation method for bacterial spores of the model organism Bacillus subtilis on beehive material. Plasma treatment was able to effectively remove spores from wax, which, under protocols currently established in veterinary practice, normally is destroyed by ignition or autoclaved for sterilization. Spores were removed from wooden surfaces with efficacies significantly higher than methods currently used in veterinary practice, such as scorching by flame treatment. In addition, we were able to non-destructively remove spores from the highly delicate honeycomb wax structures, potentially making treatment of beehive material with double inductively coupled low pressure plasma part of a fast and reliable method to rehabilitate infected bee colonies with the potential to re-use honeycombs.

Estrogenic effect of the phytoestrogen biochanin A in zebrafish, Danio rerio, and brown trout, Salmo trutta.

PubMed

Holbech, Henrik; Schröder, Kristoffer D; Nielsen, Marie L; Brande-Lavridsen, Nanna; Holbech, Bente Frost; Bjerregaard, Poul

2013-11-15

Isoflavones with estrogenic activity produced in Fabaceae plants are known to leach from agricultural areas to freshwater systems, but the effect of waterborne isoflavones in fish has not been thoroughly characterized. Therefore, the estrogenic effect of waterborne biochanin A was investigated in zebrafish (Danio rerio) and juvenile brown trout (Salmo trutta). Exposure of juvenile brown trout to 10 μg biochanin AL(-1) or higher caused marked vitellogenin induction after 9-10 days of exposure and so did exposure to 186 μg biochanin AL(-1) for 6h. Following 8d of exposure, a NOEC for induction of vitellogenin production in male zebrafish was 70 and LOEC 114 μg biochanin AL(-1). Exposure to 209 μg biochanin AL(-1) from hatch to 60 days post hatch (dph) caused a skewing of the sex ratio toward more phenotypic female zebrafish, but did not cause induction of vitellogenin in male and undifferentiated fish. (1) biochanin A elicits estrogenic effects in trout at environmentally realistic concentrations, (2) brown trout plasma vitellogenin concentrations respond to lower biochanin A exposure concentrations than vitellogenin concentrations in zebrafish homogenates and (3) concerning vitellogenin induction, the hypothesis should be tested if short term tests with zebrafish may show a higher sensitivity than partial life cycle tests. Copyright © 2013 Elsevier B.V. All rights reserved.

The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review.

PubMed

Harvey, Cliff J D C; Schofield, Grant M; Williden, Micalla

2018-01-01

Adaptation to a ketogenic diet (keto-induction) can cause unpleasant symptoms, and this can reduce tolerability of the diet. Several methods have been suggested as useful for encouraging entry into nutritional ketosis (NK) and reducing symptoms of keto-induction. This paper reviews the scientific literature on the effects of these methods on time-to-NK and on symptoms during the keto-induction phase. PubMed, Science Direct, CINAHL, MEDLINE, Alt Health Watch, Food Science Source and EBSCO Psychology and Behavioural Sciences Collection electronic databases were searched online. Various purported ketogenic supplements were searched along with the terms "ketogenic diet", "ketogenic", "ketosis" and ketonaemia (/ ketonemia). Additionally, author names and reference lists were used for further search of the selected papers for related references. Evidence, from one mouse study, suggests that leucine doesn't significantly increase beta-hydroxybutyrate (BOHB) but the addition of leucine to a ketogenic diet in humans, while increasing the protein-to-fat ratio of the diet, doesn't reduce ketosis. Animal studies indicate that the short chain fatty acids acetic acid and butyric acid, increase ketone body concentrations. However, only one study has been performed in humans. This demonstrated that butyric acid is more ketogenic than either leucine or an 8-chain monoglyceride. Medium-chain triglycerides (MCTs) increase BOHB in a linear, dose-dependent manner, and promote both ketonaemia and ketogenesis. Exogenous ketones promote ketonaemia but may inhibit ketogenesis. There is a clear ketogenic effect of supplemental MCTs; however, it is unclear whether they independently improve time to NK and reduce symptoms of keto-induction. There is limited research on the potential for other supplements to improve time to NK and reduce symptoms of keto-induction. Few studies have specifically evaluated symptoms and adverse effects of a ketogenic diet during the induction phase. Those that have typically were not designed to evaluate these variables as primary outcomes, and thus, more research is required to elucidate the role that supplementation might play in encouraging ketogenesis, improve time to NK, and reduce symptoms associated with keto-induction.

The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review

PubMed Central

Schofield, Grant M.; Williden, Micalla

2018-01-01

Background Adaptation to a ketogenic diet (keto-induction) can cause unpleasant symptoms, and this can reduce tolerability of the diet. Several methods have been suggested as useful for encouraging entry into nutritional ketosis (NK) and reducing symptoms of keto-induction. This paper reviews the scientific literature on the effects of these methods on time-to-NK and on symptoms during the keto-induction phase. Methods PubMed, Science Direct, CINAHL, MEDLINE, Alt Health Watch, Food Science Source and EBSCO Psychology and Behavioural Sciences Collection electronic databases were searched online. Various purported ketogenic supplements were searched along with the terms “ketogenic diet”, “ketogenic”, “ketosis” and ketonaemia (/ ketonemia). Additionally, author names and reference lists were used for further search of the selected papers for related references. Results Evidence, from one mouse study, suggests that leucine doesn’t significantly increase beta-hydroxybutyrate (BOHB) but the addition of leucine to a ketogenic diet in humans, while increasing the protein-to-fat ratio of the diet, doesn’t reduce ketosis. Animal studies indicate that the short chain fatty acids acetic acid and butyric acid, increase ketone body concentrations. However, only one study has been performed in humans. This demonstrated that butyric acid is more ketogenic than either leucine or an 8-chain monoglyceride. Medium-chain triglycerides (MCTs) increase BOHB in a linear, dose-dependent manner, and promote both ketonaemia and ketogenesis. Exogenous ketones promote ketonaemia but may inhibit ketogenesis. Conclusions There is a clear ketogenic effect of supplemental MCTs; however, it is unclear whether they independently improve time to NK and reduce symptoms of keto-induction. There is limited research on the potential for other supplements to improve time to NK and reduce symptoms of keto-induction. Few studies have specifically evaluated symptoms and adverse effects of a ketogenic diet during the induction phase. Those that have typically were not designed to evaluate these variables as primary outcomes, and thus, more research is required to elucidate the role that supplementation might play in encouraging ketogenesis, improve time to NK, and reduce symptoms associated with keto-induction. PMID:29576959

Cytochrome P4501A immunoassay in freshwater turtles and exposure to PCBs and environmental pollutants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yawetz, A.; Benedek-Segal, M.; Woodin, B.

1997-09-01

This is the result of a comparative study of cytochrome P4501A (CYP1A) induction in liver microsomes from three species of freshwater turtles. CYP1A induction in turtle hepatic microsomes was compared to CYP1A induction in microsomes from the alligator. Alligator mississippiensis. Treatment of two species of freshwater turtles with four consecutive intraperitoneal injections of 100 mg/kg Aroclor 1254 caused a four- to five-fold increase in P4501A in hepatic microsomes of Chrysemys picta picta and Chrysemys picta elegans. The same treatment administered to another freshwater turtle, Mauremys caspica rivulata, resulted in a very low but significant (p < 0.01) induction of P4501Amore » in hepatic microsomes. Specimens of M. caspica rivulata collected from an organic waste oxidation pond near the petrochemical industry area of the city of Ashdod exhibited normal levels of total hepatic microsomal cytochrome P450 but no detectable level of induction of cytochrome P4501A. The lack of P4501A1 induction could have resulted from two possible reasons. The first possibility is that the turtles were not exposed to residues of petrochemical waste in the pond. More likely, the apparent lack of induction resulted from the low response to CYP1A inducers found in this species. Induction of cytochrome P4501A was evaluated immunohistochemically in liver tissue of C. picta picta pretreated with Aroclor 1254 or 3,3{prime},4,4{prime}-tetrachlorobiphenyl. The most intensive staining was exhibited by sections of liver from a 3,3{prime},4,4{prime}-tetrachlorobiphenyl-treated turtle. Staining of P4501A in liver sections from Aroclor 1254-treated turtles was relatively moderate. In induced turtles, staining of the hepatocytes concentrated near the cell membranes and nuclear membranes, but stained granules were observed throughout the cytoplasm. The presence of inducible CYP1A enzymes in turtles is of importance from an evolutionary point of view and has potential ecological relevance.« less

Activation of PPARγ Ameliorates Spatial Cognitive Deficits through Restoring Expression of AMPA Receptors in Seipin Knock-Out Mice.

PubMed

Zhou, Libin; Chen, Tingting; Li, Guoxi; Wu, Chaoming; Wang, Conghui; Li, Lin; Sha, Sha; Chen, Lei; Liu, George; Chen, Ling

2016-01-27

A characteristic phenotype of congenital generalized lipodystrophy 2 (CGL2) that is caused by loss-of-function of seipin gene is mental retardation. Here, we show that seipin deficiency in hippocampal CA1 pyramidal cells caused the reduction of peroxisome proliferator-activated receptor gamma (PPARγ). Twelve-week-old systemic seipin knock-out mice and neuronal seipin knock-out (seipin-nKO) mice, but not adipose seipin knock-out mice, exhibited spatial cognitive deficits as assessed by the Morris water maze and Y-maze, which were ameliorated by the treatment with the PPARγ agonist rosiglitazone (rosi). In addition, seipin-nKO mice showed the synaptic dysfunction and the impairment of NMDA receptor-dependent LTP in hippocampal CA1 regions. The density of AMPA-induced current (IAMPA) in CA1 pyramidal cells and GluR1/GluR2 expression were significantly reduced in seipin-nKO mice, whereas the NMDA-induced current (INMDA) and NR1/NR2 expression were not altered. Rosi treatment in seipin-nKO mice could correct the decrease in expression and activity of AMPA receptor (AMPAR) and was accompanied by recovered synaptic function and LTP induction. Furthermore, hippocampal ERK2 and CREB phosphorylation in seipin-nKO mice were reduced and this could be rescued by rosi treatment. Rosi treatment in seipin-nKO mice elevated BDNF concentration. The MEK inhibitor U0126 blocked rosi-restored AMPAR expression and LTP induction in seipin-nKO mice, but the Trk family inhibitor K252a did not. These findings indicate that the neuronal seipin deficiency selectively suppresses AMPAR expression through reducing ERK-CREB activities, leading to the impairment of LTP and spatial memory, which can be rescued by PPARγ activation. Congenital generalized lipodystrophy 2 (CGL2), caused by loss-of-function mutation of seipin gene, is characterized by mental retardation. By the generation of systemic or neuronal seipin knock-out mice, the present study provides in vivo evidence that neuronal seipin deficiency causes deficits in spatial memory and hippocampal LTP induction. Neuronal seipin deficiency selectively suppresses AMPA receptor expression, ERK-CREB phosphorylation with the decline of PPARγ. The PPARγ agonist rosiglitazone can ameliorate spatial cognitive deficits and rescue the LTP induction in seipin knock-out mice by restoring AMPA receptor expression and ERK-CREB activities. Copyright © 2016 the authors 0270-6474/16/361242-12$15.00/0.

SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome.

PubMed

Shi, Chong-Shan; Qi, Hai-Yan; Boularan, Cedric; Huang, Ning-Na; Abu-Asab, Mones; Shelhamer, James H; Kehrl, John H

2014-09-15

Coronaviruses (CoV) have recently emerged as potentially serious pathogens that can cause significant human morbidity and death. The severe acute respiratory syndrome (SARS)-CoV was identified as the etiologic agent of the 2002-2003 international SARS outbreak. Yet, how SARS evades innate immune responses to cause human disease remains poorly understood. In this study, we show that a protein encoded by SARS-CoV designated as open reading frame-9b (ORF-9b) localizes to mitochondria and causes mitochondrial elongation by triggering ubiquitination and proteasomal degradation of dynamin-like protein 1, a host protein involved in mitochondrial fission. Also, acting on mitochondria, ORF-9b targets the mitochondrial-associated adaptor molecule MAVS signalosome by usurping PCBP2 and the HECT domain E3 ligase AIP4 to trigger the degradation of MAVS, TRAF3, and TRAF 6. This severely limits host cell IFN responses. Reducing either PCBP2 or AIP4 expression substantially reversed the ORF-9b-mediated reduction of MAVS and the suppression of antiviral transcriptional responses. Finally, transient ORF-9b expression led to a strong induction of autophagy in cells. The induction of autophagy depended upon ATG5, a critical autophagy regulator, but the inhibition of MAVS signaling did not. These results indicate that SARS-CoV ORF-9b manipulates host cell mitochondria and mitochondrial function to help evade host innate immunity. This study has uncovered an important clue to the pathogenesis of SARS-CoV infection and illustrates the havoc that a small ORF can cause in cells.

A randomized trial of misoprostol and oxytocin for induction of labor: safety and efficacy.

PubMed

Kramer, R L; Gilson, G J; Morrison, D S; Martin, D; Gonzales, J L; Qualls, C R

1997-03-01

To compare the safety and efficacy of misoprostol and oxytocin for induction of labor. One hundred thirty women requiring induction of labor were randomized to receive either intravenous oxytocin or 100 micrograms misoprostol, administered intravaginally every 4 hours until labor was established. Compared with women receiving oxytocin, a greater percentage of women in the misoprostol group had Bishop scores of 3 or less (58 versus 38%, P < .05). Nonetheless, the median induction-to-delivery interval was significantly shorter (585 versus 885 minutes, P < .001) in the misoprostol group. Women in the misoprostol group were more likely to deliver vaginally within 24 hours of the start of induction (77 versus 55%, P < .002). Epidural analgesia was used more frequently in women receiving oxytocin than in those receiving misoprostol (73 versus 50%, P = .025). The total percentage of cesarean deliveries was not significantly different, although the percentage of cesarean deliveries for dystocia was lower in the misoprostol group (8 versus 21%, P = .02). Uterine tachysystole was significantly more common (70 versus 11%, P < .001) and hospital charges significantly less with misoprostol. Compared with oxytocin for labor induction, misoprostol results in a shorter induction-to-delivery interval, a reduction in the rate of cesarean delivery for dystocia, and a decreased use of epidural analgesia. Uterine tachysystole is significantly more common with the use of misoprostol.

[Prostaglandins in gynecology and obstetrics].

PubMed

Klausch, B; Kyank, H

1972-06-03

A review of early research (up through 1970) on prostaglandins (PGs) is presented. Their chemical structure and classification based on their ring-structure is detailed as well as various analytic methods of mammalian tissues and body fluids. For clinical use PGE1 and 2, PGF2alpha and PGA1 are the most significant ones because of their properties. PGs have many physiological activities encompassing many organ systems. Their pharmacological actions include: 1) stimulation of nonvascular smooth muscle; 2) peripheral vasodilation (excluding PGFs which cause vasoconstriction); 3) inhibition of lipolysis; 4) inhibition of platelet aggregation; 5) inhibition of gastric peristalsis and gastric juice secretion; 6) bronchodilation; and 7) inhibition of spontaneous CNS activity. The level of PGEs in semen is closely related to the degree of fertility; normally fertile men have 55 mcg PGE/ml and never less than 11 mcg/ml. Current studies are under way on the effect of PGE in artificial insemination of sperm of subfertile men. PGF2alpha and PGE2 stimulate menstruation and uterine contraction; other PGs inhibit uterine contraction. PGs from semen have a role in sperm transport and possibly act on fallopian tube motility aiding sperm capacitation, and ovum retention and transport. Early trials with PGs point to a possible action as an abortifacient, as a once-a-month contraceptive, or a postconception contraceptive agent. PGF2alpha is found in variable concentrations in maternal blood during contraction of the pregnant uterus; levels increase as labor progresses. PGs have been used for labor induction, for induction of abortion and in mole pregnancy. Given as a constant intravenous infusion they produce regular contractions leading to natural expulsion of the fetus and causing very few side effects in the woman with no adverse effects on the fetus. PGs' action compares favorably with that of oxytocin and is preferable for labor induction in certain pregnancy complications. PGE1 and 2 have a stronger effect than PGF2alpha, hence can be used in smaller dosage and cause fewer adverse effects.

Acacia catechu Ethanolic Seed Extract Triggers Apoptosis of SCC-25 Cells.

PubMed

Lakshmi, Thangavelu; Ezhilarasan, Devaraj; Nagaich, Upendra; Vijayaragavan, Rajagopal

2017-10-01

Acacia catechu Willd ( Fabaceae ), commonly known as catechu, cachou, and black cutch, has been studied for its hepatoprotective, antipyretic, antidiarrheal, hypoglycemic, anti-inflammatory, immunomodulatory, antinociceptive, antimicrobial, free radical scavenging, and antioxidant activities. We evaluated the cytotoxic activity of ethanol extract of A. catechu seed (ACS) against SCC-25 human oral squamous carcinoma cell line. Cytotoxic effect of ACS extract was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, using concentrations of 0.1-1000 μg/mL for 24 h. A. catechu ethanol seed extract was treated SCC-25 cells with 25 and 50 μg/mL. At the end of treatment period, apoptotic marker gene expressions such as caspase 8, 9, Bcl-2, Bax, and cytochrome c were evaluated by semiquantitative reverse transcription-polymerase chain reaction. Morphological changes of ACS treated SCC-25 cells was evaluated by acridine orange/ethidium bromide (AO/EB) dual staining. Nuclear morphology and DNA fragmentation was evaluated by propidium iodide (PI) staining. A. catechu ethanol seed extract treatment caused cytotoxicity in SCC-25 cells with an IC 50 value of 100 μg/mL. Apoptotic markers caspases 8 and 9, cytochrome c, Bax gene expressions were significantly increased upon ACS extract treatment indicate the apoptosis induction in SCC-25 cells. This treatment also caused significant downregulation of Bcl-2 gene expression. Staining with AO/EB and PI shows membrane blebbing, and nuclear membrane distortion further confirms the apoptosis induction by ACS treatment in SCC-25 cells. The ethanol seed extracts of A. catechu was found to be cytotoxic at lower concentrations and induced apoptosis in human oral squamous carcinoma SCC-25 cells. Acacia catechu ethanolic seed extract contains phytochemicals such as epicatechin, rutin, and quercetin Acacia catechu seed (ACS) extract significantly ( P < 0.001) inhibits the active proliferation of human oral squamous carcinoma (SCC-25) cellsACS extract treatment to SCC-25 cells significantly modulated the gene expressions pertaining to apoptosis and propidium iodide and acridine orange/ethidium bromide staining also confirm the apoptosis inductionAntiproliferative and apoptosis inducing activities of ACS extract is correlated with phytochemical contents. Abbreviations used: ACS: Acacia catechu seed extract; MTT: 3 (4,5 dimethylthiazol 2 yl) 2,5 diphenyltetrazolium bromide; DMSO: Dimethyl sulfoxide; AO/EO: Acridine orange/ethidium bromide; LC MS: Liquid chromatography mass spectrometry.

Surface Fatigue Resistance with Induction Hardening

NASA Technical Reports Server (NTRS)

Townsend, Dennis; Turza, Alan; Chapman, Mike

1996-01-01

Induction hardening has been used for some years to harden the surface and improve the strength and service life of gears and other components. Many applications that employ induction hardening require a relatively long time to finish the hardening process and controlling the hardness of the surface layer and its depth often was a problem. Other surface hardening methods, ie., carbonizing, take a very long time and tend to cause deformations of the toothing, whose elimination requires supplementary finishing work. In double-frequency induction hardening, one uses a low frequency for the preheating of the toothed wheel and a much higher frequency for the purpose of rapidly heating the surface by way of surface hardening.

Ovulation induction in women with polycystic ovary syndrome.

PubMed

Perales-Puchalt, Alfredo; Legro, Richard S

2013-08-01

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. There are multiple ways to induce ovulation in PCOS patients, which will eventually provide a successful live birth. Each of these treatments varies in aggressiveness and effectiveness. Ranging from lifestyle modifications, through insulin-sensitizing agents, selective estrogen receptor modulators, aromatase inhibitors, gonadotropins, to laparoscopic ovarian drilling and assisted reproductive techniques, each method achieves ovulation induction through different mechanisms of action. This review provides a description and specific characteristics of the different methods used for ovulation induction which can help to design a personalized approach to each PCOS patient, and a general stepwise approach to ovulation induction in these patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Tenascin C protects aorta from acute dissection in mice

PubMed Central

Kimura, Taizo; Shiraishi, Kozoh; Furusho, Aya; Ito, Sohei; Hirakata, Saki; Nishida, Norifumi; Yoshimura, Koichi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Ikeda, Yasuhiro; Miyamoto, Takanobu; Ueno, Takafumi; Hamano, Kimikazu; Hiroe, Michiaki; Aonuma, Kazutaka; Matsuzaki, Masunori; Imaizumi, Tsutomu; Aoki, Hiroki

2014-01-01

Acute aortic dissection (AAD) is caused by the disruption of intimomedial layer of the aortic walls, which is immediately life-threatening. Although recent studies indicate the importance of proinflammatory response in pathogenesis of AAD, the mechanism to keep the destructive inflammatory response in check is unknown. Here, we report that induction of tenascin-C (TNC) is a stress-evoked protective mechanism against the acute hemodynamic and humoral stress in aorta. Periaortic application of CaCl2 caused stiffening of abdominal aorta, which augmented the hemodynamic stress and TNC induction in suprarenal aorta by angiotensin II infusion. Deletion of Tnc gene rendered mice susceptible to AAD development upon the aortic stress, which was accompanied by impaired TGFβ signaling, insufficient induction of extracellular matrix proteins and exaggerated proinflammatory response. Thus, TNC works as a stress-evoked molecular damper to maintain the aortic integrity under the acute stress. PMID:24514259

Divergent creative thinking in young and older adults: Extending the effects of an episodic specificity induction.

PubMed

Madore, Kevin P; Jing, Helen G; Schacter, Daniel L

2016-08-01

Recent research has suggested that an episodic specificity induction-brief training in recollecting the details of a past experience-enhances divergent creative thinking on the alternate uses task (AUT) in young adults, without affecting performance on tasks thought to involve little divergent thinking; however, the generalizability of these results to other populations and tasks is unknown. In the present experiments, we examined whether the effects of an episodic specificity induction would extend to older adults and a different index of divergent thinking, the consequences task. In Experiment 1, the specificity induction significantly enhanced divergent thinking on the AUT in both young and older adults, as compared with a control induction not requiring specific episodic retrieval; performance on a task involving little divergent thinking (generating associates for common objects) did not vary as a function of induction. No overall age-related differences were observed on either task. In Experiment 2, the specificity induction significantly enhanced divergent thinking (in terms of generating consequences of novel scenarios) in young adults, relative to another control induction not requiring episodic retrieval. To examine the types of creative ideas affected by the induction, the participants in both experiments also labeled each of their divergent-thinking responses as an "old idea" from memory or a "new idea" from imagination. New, and to some extent old, ideas were significantly boosted following the specificity induction relative to the control. These experiments provide novel evidence that an episodic specificity induction can boost divergent thinking in young and older adults, and indicate that episodic memory is involved in multiple divergent-thinking tasks.

Divergent creative thinking in young and older adults: Extending the effects of an episodic specificity induction

PubMed Central

Madore, Kevin P.; Jing, Helen G.; Schacter, Daniel L.

2016-01-01

Recent research has suggested that an episodic specificity induction- brief training in recollecting the details of a past experience- enhances divergent creative thinking on the Alternate Uses Task (AUT) in young adults without affecting performance on tasks thought to involve little divergent thinking, but the generalizability of these results to other populations and tasks is unknown. The present experiments examined whether effects of an episodic specificity induction extend to older adults and a different index of divergent thinking, the Consequences Task. In Experiment 1, the specificity induction significantly enhanced divergent thinking on the AUT in both young and older adults compared with a control induction not requiring specific episodic retrieval; performance on a task involving little divergent thinking did not vary as a function of induction (generating associates for common objects). No overall age-related differences were observed on either task. In Experiment 2, the specificity induction significantly enhanced divergent thinking (generating consequences of novel scenarios) in young adults compared with another control induction not requiring episodic retrieval. To examine the types of creative ideas affected by the induction, participants in both experiments also labeled each of their divergent thinking responses as an old idea from memory or new idea from imagination. New and to some extent old ideas were significantly boosted following the specificity induction compared with the control. These experiments provide novel evidence that an episodic specificity induction can boost divergent thinking in young and older adults, and indicate that episodic memory is involved in multiple divergent thinking tasks. PMID:27001170

Usefulness of elastography in predicting the outcome of Foley catheter labour induction.

PubMed

Wozniak, Slawomir; Czuczwar, Piotr; Szkodziak, Piotr; Paszkowski, Tomasz

2015-06-01

Incorrect selection of women for labour induction may increase the risk of caesarean section and other postpartum and neonatal complications. It has been recently shown that elastography of the uterine cervix holds the potential to predict the outcome of pharmacological labour induction. There are no data on the usefulness of elastography in predicting the outcome of mechanical induction of labour. To assess the usefulness of elastographic cervical assessment in predicting the success of Foley catheter labour induction. This prospective observational study included 39 pregnant women at term with an unfavourable cervix (Bishop score ≤ 6) suitable for Foley catheter labour induction. Before labour induction the following data were recorded: Bishop score, cervical length (measured by ultrasound) and the stiffness of cervical internal os, canal and external os assessed by elastography (elastography index - EI). Statistical relationships between pre-interventional assessment of the cervix and outcome of Foley catheter labour induction (successful induction, time to delivery and route of delivery) were analysed. EI's of internal cervical os and cervical canal were significantly lower (softer) in women with successful labour induction and vaginal delivery, while EI's of the external cervical os, Bishop score and cervix length were not significantly different. Time to vaginal delivery was significantly correlated with the EI's of internal cervical os, cervical canal and Bishop score, but not with EI's of the external cervical os and cervix length. Elastography has the potential to predict the outcome of Foley catheter labour induction. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Induction and transfer of resistance to poisoning by Amorimia pubiflora in sheep with non-toxic doses of the plant and ruminal content

USDA-ARS?s Scientific Manuscript database

Amorimia pubiflora (Malpighiaceae), which contains sodium monofluoroacetate (MFA) is the main cause of “sudden death” in cattle in the Brazilian state of Mato Grosso. This research investigated the induction of resistance to the poisoning in sheep by the continuous administration of non-toxic doses ...

Systemic Induction of the Small Antibacterial Compound in the Leaf Exudate During Benzothiadiazole-elicited Systemic Acquired Resistance in Pepper

PubMed Central

Lee, Boyoung; Park, Yong-Soon; Yi, Hwe-Su; Ryu, Choong-Min

2013-01-01

Plants protect themselves from diverse potential pathogens by induction of the immune systems such as systemic acquired resistance (SAR). Most bacterial plant pathogens thrive in the intercellular space (apoplast) of plant tissues and cause symptoms. The apoplastic leaf exudate (LE) is believed to contain nutrients to provide food resource for phytopathogenic bacteria to survive and to bring harmful phytocompounds to protect plants against bacterial pathogens. In this study, we employed the pepper-Xanthomonas axonopodis system to assess whether apoplastic fluid from LE in pepper affects the fitness of X. axonopodis during the induction of SAR. The LE was extracted from pepper leaves 7 days after soil drench-application of a chemical trigger, benzothiadiazole (BTH). Elicitation of plant immunity was confirmed by significant up-regulation of four genes, CaPR1, CaPR4, CaPR9, and CaCHI2, by BTH treatment. Bacterial fitness was evaluated by measuring growth rate during cultivation with LE from BTH- or water-treated leaves. LE from BTH-treatment significantly inhibited bacterial growth when compared to that from the water-treated control. The antibacterial activity of LE from BTH-treated samples was not affected by heating at 100°C for 30 min. Although the antibacterial molecules were not precisely identified, the data suggest that small (less than 5 kDa), heat-stable compound(s) that are present in BTH-induced LE directly attenuate bacterial growth during the elicitation of plant immunity. PMID:25288963

Magnetic properties of electrical iron sheet under controlled magnetization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takada, Shunji; Sasaki, Tadashi

1993-11-01

Power losses of electrical iron sheet were measured under the controlled magnetizing condition in which magnetic induction changes at a constant time rate for a fixed time and pauses at a certain induction for a varied time in every half magnetizing cycle. Considerable increase of losses per magnetizing cycle with a pause time has been found only in the case of magnetization pause at the maximum induction. The increase of losses is considered from magnetostriction measurements to be caused by internal magnetization rearrangement accompanied with flux reversal after the pause period.

Characterization of the photosynthetic induction response in a Populus species with stomata barely responding to light changes.

PubMed

Tang, Y; Liang, N

2000-08-01

The photosynthetic induction response is constrained by stomatal and biochemical limitations. However, leaves in some plants like Populus koreana x trichocarpa cv. Peace (a hybrid clone) may have little stomatal limitation because their stomata barely respond to changes in photon flux density (PFD). We examined the induction responses of leaves of well-watered and dehydrated P. koreana x trichocarpa plants grown in a high-light or a low-light regime. With an increase in PFD from 50 to 500 micromol m(-2) s(-1), steady-state stomatal conductance (g(s)) increased by only 0.25-8.2%, regardless of the initial g(s), but steady-state assimilation rate (A) increased by 550-1810%. Photosynthetic induction times required to reach 50% (IT50) and 90% (IT90) of A at high PFD were 60-90 s and 210-360 s, respectively. Examination of the dynamic relationships between A and g(s), and between A and intercellular CO2 concentration, indicated that the induction limitation was imposed completely by the biochemical components within 30-40 s after the PFD increase. Values of IT50 and IT90 were significantly higher in low-light leaves than in high-light leaves, whereas the induction state at 60 s and the induction efficiency at 60 and 120 s after the increase in PFD were lower in low-light leaves than in high-light leaves. Dehydration reduced leaf water potential (psi) significantly, resulting in a significantly decreased initial g(s). Leaf water potential had no significant effects on induction time in high-light leaves, but a low psi significantly reduced the induction time in low-light leaves. We conclude that the photosynthetic induction response was limited almost completely by biochemical components because the stomata barely responded to light changes. The biochemical limitation appeared to be higher in low-light leaves than in high-light leaves. Mild water stress may have reduced steady-state A and g(s), but it had little effect on the photosynthetic induction response in high-light leaves.

Hyaluronidase as an adjunct in an immobilizing mixture for moose.

PubMed

Haigh, J C

1979-11-01

Hyaluronidase was put into immobilizing syringes for 58 of 104 moose captured with a fentanyl/xylazine mixture. Induction times were measured for both groups and were related to injection site as well as drug mixture. Hyaluronidase-treated moose had significantly shorter induction times than others. Injection site also had a significant effect on induction times.

Clinical and histologic effects of intracardiac administration of propofol for induction of anesthesia in ball pythons (Python regius).

PubMed

McFadden, Michael S; Bennett, R Avery; Reavill, Drury R; Ragetly, Guillaume R; Clark-Price, Stuart C

2011-09-15

To assess the clinical differences between induction of anesthesia in ball pythons with intracardiac administration of propofol and induction with isoflurane in oxygen and to assess the histologic findings over time in hearts following intracardiac administration of propofol. Prospective randomized study. 30 hatchling ball pythons (Python regius). Anesthesia was induced with intracardiac administration of propofol (10 mg/kg [4.5 mg/lb]) in 18 ball pythons and with 5% isoflurane in oxygen in 12 ball pythons. Induction time, time of anesthesia, and recovery time were recorded. Hearts from snakes receiving intracardiac administration of propofol were evaluated histologically 3, 7, 14, 30, and 60 days following propofol administration. Induction time with intracardiac administration of propofol was significantly shorter than induction time with 5% isoflurane in oxygen. No significant differences were found in total anesthesia time. Recovery following intracardiac administration of propofol was significantly longer than recovery following induction of anesthesia with isoflurane in oxygen. Heart tissue evaluated histologically at 3, 7, and 14 days following intracardiac administration of propofol had mild inflammatory changes, and no histopathologic lesions were seen 30 and 60 days following propofol administration. Intracardiac injection of propofol in snakes is safe and provides a rapid induction of anesthesia but leads to prolonged recovery, compared with that following induction with isoflurane. Histopathologic lesions in heart tissues following intracardiac injection of propofol were mild and resolved after 14 days.

How far can attraction-caused misalignment account for the Morinaga misalignment effect?

PubMed

Hotopf, W H; Brown, S

1990-01-01

When a line (the pointer) is collinear with a dot, the addition of a second line (the induction line) contiguous with the dot or near it may cause the pointer to appear to be collinear with a point further along or nearer to the induction line. The geometrical relations upon which this effect (which we call attraction-caused misalignment) depends, have been studied with the Obonai and Wundt-Loeb (Hotopf, 1981; Hotopf & Brown, 1988) figures. Drawing upon the studies of misalignment in the Morinaga figure carried out by Restle (1976), Day, Bellamy, and Norman (1983), and Day and Kasperczyk (1985), as well as upon two new experiments, we show that misalignment in the Morinaga figure is also attraction-caused misalignment, as previously defined. We conclude with a discussion of a number of theories that aim at accounting for attraction misalignment.

Metoprolol decreases the plasma exposure of metformin via the induction of liver, kidney and muscle uptake in rats.

PubMed

Ma, Yan-Rong; Shi, A-Xi; Qin, Hong-Yan; Zhang, Tiffany; Wu, Yan-Fang; Zhang, Guo-Qiang; Wu, Xin-An

2016-12-01

Drug interactions are one of the commonest causes of side effects, particularly in long-term therapy. The aim of the current study was to investigate the possible effects of metoprolol on the pharmacokinetics of metformin in rats and to clarify the mechanism of drug interaction. In this study, rats were treated with metformin alone or in combination with metoprolol. Plasma, urine and tissue concentrations of metformin were determined by HPLC. Western blotting and real-time qPCR were used to evaluate the expression of rOCTs and rMATE1. The results showed that, after single or 7-day repeated administration, the plasma concentrations of metformin in the co-administration group were significantly decreased compared with that in the metformin group. However, the parameter V/F of metformin in the co-administration group was markedly increased compared with that in the metformin group. The hepatic, renal and muscular K p of metformin were markedly elevated after co-administration with metoprolol. Consistently, metformin uptake in rat kidney slices was significantly induced by metoprolol. In addition, multiple administrations of metoprolol significantly reduced the expression of rMATE1 in rat kidney as well as the urinary excretion of metformin. Importantly, after long-term administration, lactic acid and uric acid levels in the co-administration group were increased by 25% and 26%, respectively, compared with that in the metformin group. These results indicate that metoprolol can decrease the plasma concentration of metformin via the induction of hepatic, renal and muscular uptake, and long-term co-administration of metformin and metoprolol can cause elevated lactic acid and uric acid levels. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Induction of nuclear anomalies in exfoliated buccal cells of coca chewers: results of a field study.

PubMed

Nersesyan, Armen; Kundi, Michael; Krupitza, Georg; Barcelos, Gustavo; Mišík, Miroslav; Wultsch, Georg; Carrion, Juan; Carrion-Carrera, Gladys; Knasmueller, Siegfried

2013-03-01

The leaves of coca (Erythroxylum coca var. coca), a South American shrub which contains cocaine, other alkaloids and phenolics are widely used by indigenous populations of the Andes. It is currently not known if coca consumption causes genotoxic effects in humans. This information is important to predict potential long-term toxic effects such as cancer induction. Therefore, the buccal cytome assay was used to analyze oral cells from 45 uni- and bilateral chewers and 23 controls living in the Altiplano of the Peruvian Andes. In total, 123,471 cells were evaluated from chewers and 57,916 from controls. Information concerning the consumption levels and habits and also use of lime were collected with questionnaires. Chewing of the leaves did not induce nuclear anomalies reflecting genetic damage such as micronuclei (MNi) and nuclear buds; in the highest exposure group (but not in the overall group) even a significant decrease in the frequencies of cells with MNi (by 64 %) was observed. However, we found significantly elevated levels of other nuclear anomalies (karyorrhexis and karyolysis) which reflect cytotoxic effects in the coca users. The frequencies of these anomalies increased with the daily consumption and when lime was used to improve the release of the alkaloids. In contrast to other chewing habits (betel, tobacco and khat), consumption of coca leaves does not induce genetic instability in cells from the oral cavity and our findings indicate that no adverse health effects take place in chewers which are associated with DNA damage. However, the significant increase in certain anomalies shows that acute toxic effects are caused by coca consumption.

Gallic acid reduces cell growth by induction of apoptosis and reduction of IL-8 in HepG2 cells.

PubMed

Lima, Kelly Goulart; Krause, Gabriele Catyana; Schuster, Aline Daniele; Catarina, Anderson Velasque; Basso, Bruno Souza; De Mesquita, Fernanda Cristina; Pedrazza, Leonardo; Marczak, Elisa Simon; Martha, Bianca Andrade; Nunes, Fernanda Bordignon; Chiela, Eduardo Cremonese Filippi; Jaeger, Natália; Thomé, Marcos Paulo; Haute, Gabriela Viegas; Dias, Henrique Bregolin; Donadio, Márcio Vinícius Fagundes; De Oliveira, Jarbas Rodrigues

2016-12-01

Hepatocellular carcinoma is the most prevalent primary liver tumor and is among the top ten cancer that affect the world population. Its development is related, in most cases, to the existence of chronic liver injury, such as in cirrhosis. The knowledge about the correlation between chronic inflammation and cancer has driven new researches with anti-inflammatory agents that have potential for the development of antitumor drugs. Gallic acid is a phenolic acid found in many natural products and have shown anti-inflammatory, anti-tumor, anti-mutagenic and antioxidant actions. The purpose of this study was to investigate the effect of gallic acid on acute and chronic cell proliferation and inflammatory parameters of hepatocellular carcinoma cells (HepG2), as well as to investigate the mechanisms involved. Results showed that the gallic acid decreased the proliferation of HepG2 cells in a dose-dependent manner (Trypan blue exclusion assay), without causing necrosis (LDH assay). We observed a significant increase in the percentage of small and regular nuclei (Nuclear Morphometric Analysis assay), a significant induction of apoptosis by Annexin V-FITC and PI assay and no interference with the cell cycle using the FITC BrdU Flow Kit. We observed a significant reduction in the levels of IL-8 and increased levels of IL-10 and IL-12 (Cytometric Bead Array Human Inflammation Assay). Furthermore, gallic acid caused no cancer cells regrowth at a long term (Cumulative Population Doubling assay). According to these results, gallic acid showed a strong potential as an anti-tumor agent in hepatocellular carcinoma cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Extract of Citrus maxima (pummelo) leaves improve hepatoprotective activity in Wistar rats submitted to the induction of non-alcoholic hepatic steatosis.

PubMed

Feksa, Denise Lima; Coelho, Ritiéle Pinto; Aparecida da Costa Güllich, Angélica; Dal Ponte, Emanuelle S; da Costa Escobar Piccoli, Jacqueline; Manfredini, Vanusa

2018-02-01

Non-alcoholic fatty liver disease is a spectrum of liver changes, ranging from hepatic steatosis to hepatocellular carcinoma. The Citrus maxima (CM) has been shown to be beneficial to the organism, and these activities are attributed to the presence of phytochemical compounds. The objective of this study was to evaluate the n vitro antioxidant potential of the CM leaves extract and on Wistar rats submitted to hepatic steatosis induction by fructose-associated hyperlipid diet (FHD). For the evaluation of in vivo effects, the animals were distributed in G1 (normal diet - ND), G2 (FHD), G3 (ND + extract 50mg/kg) and G4 (FHD + extract 50 mg/kg). All the parameters were determined through classical methodologies. The extract showed a significant antioxidant potential in vitro. In the in vivo analysis, the diet used was able to induce the development of metabolic abnormalities that favored the formation of hepatic steatosis (G2). Changes in inflammatory markers, increase in markers of oxidative damage, and reduction of antioxidant defenses were also observed. In addition, the extract did not cause changes in the animals' weight gain and acted as an anti-inflammatory, since G4 animals exhibited significantly reduced levels of the inflammatory markers. In the liver, the extract significantly decreased the content of fat, cholesterol and triglycerides compared to G2. The extract also showed antioxidant activity (G4) when compared to G2. The results suggest that the extract of CM leaf showed hepatoprotective, hypolipidemic, anti-inflammatory and antioxidant activities and the presence of phenolic compounds is a probable cause for such activities. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

An analysis of nonlinear dynamics underlying neural activity related to auditory induction in the rat auditory cortex.

PubMed

Noto, M; Nishikawa, J; Tateno, T

2016-03-24

A sound interrupted by silence is perceived as discontinuous. However, when high-intensity noise is inserted during the silence, the missing sound may be perceptually restored and be heard as uninterrupted. This illusory phenomenon is called auditory induction. Recent electrophysiological studies have revealed that auditory induction is associated with the primary auditory cortex (A1). Although experimental evidence has been accumulating, the neural mechanisms underlying auditory induction in A1 neurons are poorly understood. To elucidate this, we used both experimental and computational approaches. First, using an optical imaging method, we characterized population responses across auditory cortical fields to sound and identified five subfields in rats. Next, we examined neural population activity related to auditory induction with high temporal and spatial resolution in the rat auditory cortex (AC), including the A1 and several other AC subfields. Our imaging results showed that tone-burst stimuli interrupted by a silent gap elicited early phasic responses to the first tone and similar or smaller responses to the second tone following the gap. In contrast, tone stimuli interrupted by broadband noise (BN), considered to cause auditory induction, considerably suppressed or eliminated responses to the tone following the noise. Additionally, tone-burst stimuli that were interrupted by notched noise centered at the tone frequency, which is considered to decrease the strength of auditory induction, partially restored the second responses from the suppression caused by BN. To phenomenologically mimic the neural population activity in the A1 and thus investigate the mechanisms underlying auditory induction, we constructed a computational model from the periphery through the AC, including a nonlinear dynamical system. The computational model successively reproduced some of the above-mentioned experimental results. Therefore, our results suggest that a nonlinear, self-exciting system is a key element for qualitatively reproducing A1 population activity and to understand the underlying mechanisms. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Electric Field Feature of Moving Magnetic Field

NASA Astrophysics Data System (ADS)

Chen, You Jun

2001-05-01

A new fundamental relationship of electric field with magnetic field has been inferred from the fundamental experimental laws and theories of classical electromagnetics. It can be described as moving magnetic field has or gives electric feature. When a field with magnetic induction of B moves in the velocity of V, it will show electric field character, the electric field intensity E is E = B x V and the direction of E is in the direction of the vector B x V. It is improper to use the time-varying electromagnetics theories as the fundamental theory of the electromagnetics and group the electromagnetic field into static kind and time-varying kind for the static is relative to motional not only time-varying. The relationship of time variation of magnetic field induction or magnetic flux with electric field caused by magnetic field is fellowship not causality. Thus time-varying magnetic field can cause electric field is not a nature principle. Sometime the time variation of magnetic flux is equal to the negative electromotive force or the time variation of magnetic field induction is equal to the negative curl of electric field caused by magnetic field motion, but not always. And not all motion of magnetic field can cause time variation of magnetic field. Therefore Faraday-Lenz`s law can only be used as mathematics tool to calculate the quantity relation of the electricity with the magnetism in some case like the magnetic field moving in uniform medium. Faraday-Lenz`s law is unsuitable to be used in moving uniform magnetic field or there is magnetic shield. Key word: Motional magnetic field, Magnetic induction, Electric field intensity, Velocity, Faraday-Lenz’s law

Npro of classical swine fever virus contributes to pathogenicity in pigs by preventing type I interferon induction at local replication sites.

PubMed

Tamura, Tomokazu; Nagashima, Naofumi; Ruggli, Nicolas; Summerfield, Artur; Kida, Hiroshi; Sakoda, Yoshihiro

2014-04-17

Classical swine fever (CSF) caused by CSF virus (CSFV) is a highly contagious disease of pigs. The viral protein Npro of CSFV interferes with alpha- and beta-interferon (IFN-α/β) induction by promoting the degradation of interferon regulatory factor 3 (IRF3). During the establishment of the live attenuated CSF vaccine strain GPE-, Npro acquired a mutation that abolished its capacity to bind and degrade IRF3, rendering it unable to prevent IFN-α/β induction. In a previous study, we showed that the GPE- vaccine virus became pathogenic after forced serial passages in pigs, which was attributed to the amino acid substitutions T830A in the viral proteins E2 and V2475A and A2563V in NS4B. Interestingly, during the re-adaptation of the GPE- vaccine virus in pigs, the IRF3-degrading function of Npro was not recovered. Therefore, we examined whether restoring the ability of Npro to block IFN-α/β induction of both the avirulent and moderately virulent GPE--derived virus would enhance pathogenicity in pigs. Viruses carrying the N136D substitution in Npro regained the ability to degrade IRF3 and suppress IFN-α/β induction in vitro. In pigs, functional Npro significantly reduced the local IFN-α mRNA expression in lymphoid organs while it increased quantities of IFN-α/β in the circulation, and enhanced pathogenicity of the moderately virulent virus. In conclusion, the present study demonstrates that functional Npro influences the innate immune response at local sites of virus replication in pigs and contributes to pathogenicity of CSFV in synergy with viral replication.

Induction of Hydrolytic Enzymes in Brassica campestris in Response to Pathovars of Xanthomonas campestris.

PubMed

Conrads-Strauch, J; Dow, J M; Milligan, D E; Parra, R; Daniels, M J

1990-05-01

Inoculation of mature leaves of turnip (Brassica campestris) with the incompatible Xanthomonas campestris pv vitians resulted in the induction of beta-1,3-glucanase and chitinase/lysozyme (CHL) activity. No increase in the basal activity of beta-1,3-glucanase was observed after inoculation of leaves with heat- or rifampicin-killed X. c. vitians, Escherichia coli, or sterile water. Inoculation with the compatible X. campestris pv campestris resulted in a slower induction of glucanase than that seen with X. c. vitians. In contrast, all bacteria caused an induction of CHL activity. One major beta-1,3-glucanase (molecular mass 36.5 kilodaltons, isoelectric point [pl] ~8.5) was purified from both inoculated and untreated leaves by ion-exchange chromatography. The enzyme degraded laminarin by an endo-glycolytic mechanism. Two major CHL isozymes (CHL 1 and CHL 2, molecular mass 30 kilodaltons and pl 9.4 and 10.2, respectively) were purified from X. c. vitians inoculated leaves by affinity chromatography on a chitin column followed by ion-exchange chromatography. Both enzymes degraded chitin by an endo-glycolytic mechanism although the ratio of lysozyme to chitinase specific activities for CHL 1 and CHL2 were different. The induction of CHL 1 was associated with the hypersensitive reaction caused by X. c. vitians whereas all other treatments induced largely CHL 2.

Insulin protects against hepatic damage postburn.

PubMed

Jeschke, Marc G; Kraft, Robert; Song, Juquan; Gauglitz, Gerd G; Cox, Robert A; Brooks, Natasha C; Finnerty, Celeste C; Kulp, Gabriela A; Herndon, David N; Boehning, Darren

2011-01-01

Burn injury causes hepatic dysfunction associated with endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR). ER stress/UPR leads to hepatic apoptosis and activation of the Jun-N-terminal kinase (JNK) signaling pathway, leading to vast metabolic alterations. Insulin has been shown to attenuate hepatic damage and to improve liver function. We therefore hypothesized that insulin administration exerts its effects by attenuating postburn hepatic ER stress and subsequent apoptosis. Male Sprague Dawley rats received a 60% total body surface area (TBSA) burn injury. Animals were randomized to receive saline (controls) or insulin (2.5 IU/kg q. 24 h) and euthanized at 24 and 48 h postburn. Burn injury induced dramatic changes in liver structure and function, including induction of the ER stress response, mitochondrial dysfunction, hepatocyte apoptosis, and up-regulation of inflammatory mediators. Insulin decreased hepatocyte caspase-3 activation and apoptosis significantly at 24 and 48 h postburn. Furthermore, insulin administration decreased ER stress significantly and reversed structural and functional changes in hepatocyte mitochondria. Finally, insulin attenuated the expression of inflammatory mediators IL-6, MCP-1, and CINC-1. Insulin alleviates burn-induced ER stress, hepatocyte apoptosis, mitochondrial abnormalities, and inflammation leading to improved hepatic structure and function significantly. These results support the use of insulin therapy after traumatic injury to improve patient outcomes.

Insulin Protects against Hepatic Damage Postburn

PubMed Central

Jeschke, Marc G; Kraft, Robert; Song, Juquan; Gauglitz, Gerd G; Cox, Robert A; Brooks, Natasha C; Finnerty, Celeste C; Kulp, Gabriela A; Herndon, David N; Boehning, Darren

2011-01-01

Burn injury causes hepatic dysfunction associated with endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR). ER stress/UPR leads to hepatic apoptosis and activation of the Jun-N-terminal kinase (JNK) signaling pathway, leading to vast metabolic alterations. Insulin has been shown to attenuate hepatic damage and to improve liver function. We therefore hypothesized that insulin administration exerts its effects by attenuating postburn hepatic ER stress and subsequent apoptosis. Male Sprague Dawley rats received a 60% total body surface area (TBSA) burn injury. Animals were randomized to receive saline (controls) or insulin (2.5 IU/kg q. 24 h) and euthanized at 24 and 48 h postburn. Burn injury induced dramatic changes in liver structure and function, including induction of the ER stress response, mitochondrial dysfunction, hepatocyte apoptosis, and up-regulation of inflammatory mediators. Insulin decreased hepatocyte caspase-3 activation and apoptosis significantly at 24 and 48 h postburn. Furthermore, insulin administration decreased ER stress significantly and reversed structural and functional changes in hepatocyte mitochondria. Finally, insulin attenuated the expression of inflammatory mediators IL-6, MCP-1, and CINC-1. Insulin alleviates burn-induced ER stress, hepatocyte apoptosis, mitochondrial abnormalities, and inflammation leading to improved hepatic structure and function significantly. These results support the use of insulin therapy after traumatic injury to improve patient outcomes. PMID:21267509

Effects of dexmedetomidine on heart arrhythmia prevention in off-pump coronary artery bypass surgery: A randomized clinical trial.

PubMed

Soltani, Ghasem; Jahanbakhsh, Saeed; Tashnizi, Mohammad Abbasi; Fathi, Mehdi; Amini, Shahram; Zirak, Nahid; Sheybani, Shima

2017-10-01

Arrhythmia occurring during and after surgery is one of the major complications in open-heart surgery. Dexmedetomidine is an intravenous alpha-2 agonist and very specific short-acting drug to protect the various organs against ischemic injuries and blood reflow. However, the effect of dexmedetomidine for preventing intraoperative heart arrhythmias has not been recognized. This study aimed to determine the effect of dexmedetomidine on the incidence rate of heart arrhythmias and anesthetic required in off-pump coronary artery bypass surgery. This randomized clinical trial was conducted on patients who were candidates for off-pump coronary artery bypass referring to Imam Reza Hospital of Mashhad, Iran, from July 2016 through January 2017. The patients were randomly assigned to two groups of intervention (infusion of 0.5 mcg/kg/h dexmedetomidine together with induction followed by infusion of 0.5 mcg/kg/h by the end of the surgery) or control (saline infusion). Mean arterial pressure (MAP) and heart rate (HR) were measured before induction, during surgery operation and ICU admission. Data were analyzed by SPSS version 18 using Chi Square and independent-samples t-test. A total of 76 patients with a mean age of 59.8 ± 8.2 years (in two groups of 38) were studied. The two groups had no statistically significant difference in terms of background variables. The MAP and HR values before induction, during surgery and ICU admission were significantly higher in the control group than in the intervention group (p=0.001). Out of the studied arrhythmias, the values of PAC (55.2% vs. 15.7%), PVC (81.5% vs. 21.0%), AF (26.3% vs. 7.8%), VTAC (21.0% vs. 2.6%) were significantly lower in dexmedetomidine group (p=0.001). It seems that dexmedetomidine administration during induction and surgery can cause significant reduction in most of the common arrhythmias in off-pump coronary bypass surgery. The use of dexmedetomidine maintains MAP and HR at significantly lower values, and changes compared to the control group as well as reduces the need for anesthetic compounds. The present study has been registered at the Iranian Registry of Clinical Trials (www.IRCT.IR) with a code of IRCT2016072413159N9 before starting the study. This study was fully sponsored by the Research Deputy at Mashhad University of Medical Sciences, Iran (grant number 941413).

Cereal crop volatile organic compound induction after mechanical injury, beetle herbivory (Oulema spp.), or fungal infection (Fusarium spp.).

PubMed

Piesik, Dariusz; Pańka, Dariusz; Delaney, Kevin J; Skoczek, Agata; Lamparski, Robert; Weaver, David K

2011-06-15

Herbivory, mechanical injury or pathogen infestation to vegetative tissues can induce volatile organic compounds (VOCs) production, which can provide defensive functions to injured and uninjured plants. In our studies with 'McNeal' wheat, 'Otana' oat, and 'Harrington' barley, plants that were mechanically injured, attacked by either of two Oulema spp. (melanopus or cyanella) beetles, or infected by one of the three Fusarium spp. (graminearum, avenaceum, or culmorum), had significant VOC induction compared to undamaged plants. Mechanical injury to the main stem or one leaf caused the induction of one green leaf volatile (GLV) - (Z)-3-hexenol, and three terpenes (β-linalool, β-caryophyllene, and α-pinene) with all three grasses; wheat and barley also showed β-linalool oxide induction. The blend of induced VOCs after Fusarium spp. infestation or Oulema spp. herbivory was dominated by GLVs ((Z)-3-hexenal, (E)-2-hexenal, (E)-2-hexenol, (Z)-3-hexenyl acetate, and 1-hexenyl acetate) and β-linalool and β-caryophyllene; beetle herbivory also induced (E)-β-farnesene. Different ratios of individual VOCs were induced between the two Oulema spp. for each cereal grass and different ratios across the three cereals for each beetle species. Also, different ratios of individual VOCs were induced between the three Fusarium spp. for each cereal grass and different ratios across the three cereals for each fungal pathogen species. Our results are preliminary since we could not simultaneously measure VOC induction from controls with each of the ten different injury treatments for each of the three cereals. However, the comparison of mechanical injury, insect herbivory, and fungal infection has not been previously examined with VOC responses from three different plant species within the same family. Also, our work suggests large qualitative and quantitative overlap of VOC induction from plants of all three cereals having beetle herbivory injury when compared to infection injury from necrotrophic fungal pathogens. Copyright © 2010 Elsevier GmbH. All rights reserved.

Science 101: What Causes Electromagnetic Induction?

ERIC Educational Resources Information Center

Robertson, Bill

2013-01-01

Electromagnetic induction is the technical name for the fact that, when a wire is moved near a magnet or a magnet is moved near a wire, an electric current flows in the wire. Although Bill Robertson honestly admits to not knowing why this happens, he does say that it is possible to get a deeper understanding of what's going on in terms of…

Polyunsaturated fat in the methionine-choline-deficient diet influences hepatic inflammation but not hepatocellular injury.

PubMed

Lee, Gene S; Yan, Jim S; Ng, Raymond K; Kakar, Sanjay; Maher, Jacquelyn J

2007-08-01

Methionine-choline-deficient (MCD) diets that cause steatohepatitis in rodents are typically enriched in polyunsaturated fat. To determine whether the fat composition of the MCD formula influences the development of liver disease, we manufactured custom MCD formulas with fats ranging in PUFA content from 2% to 59% and tested them for their ability to induce steatohepatitis. All modified-fat MCD formulas caused identical degrees of hepatic steatosis and resulted in a similar distribution of fat within individual hepatic lipid compartments. The fatty acid composition of hepatic lipids, however, reflected the fat composition of the diet. Mice fed a PUFA-rich MCD formula showed extensive hepatic lipid peroxidation, induction of proinflammatory genes, and histologic inflammation. When PUFAs were substituted with more saturated fats, lipid peroxidation, proinflammatory gene induction, and hepatic inflammation all declined significantly. Despite the close relationship between PUFAs and hepatic inflammation in mice fed MCD formulas, dietary fat had no impact on MCD-mediated damage to hepatocytes. Indeed, histologic apoptosis and serum alanine aminotransferase levels were comparable in all MCD-fed mice regardless of dietary fat content. Together, these results indicate that dietary PUFAs promote hepatic inflammation but not hepatotoxicity in the MCD model of liver disease. These findings emphasize that individual dietary nutrients can make specific contributions to steatohepatitis.

The Influence of Lead on Generation of Signalling Molecules and Accumulation of Flavonoids in Pea Seedlings in Response to Pea Aphid Infestation.

PubMed

Woźniak, Agnieszka; Drzewiecka, Kinga; Kęsy, Jacek; Marczak, Łukasz; Narożna, Dorota; Grobela, Marcin; Motała, Rafał; Bocianowski, Jan; Morkunas, Iwona

2017-08-24

The aim of this study was to investigate the effect of an abiotic factor, i.e., lead at various concentrations (low causing a hormesis effect and causing high toxicity effects), on the generation of signalling molecules in pea ( Pisum sativum L. cv. Cysterski) seedlings and then during infestation by the pea aphid ( Acyrthosiphon pisum Harris). The second objective was to verify whether the presence of lead in pea seedling organs and induction of signalling pathways dependent on the concentration of this metal trigger defense responses to A. pisum . Therefore, the profile of flavonoids and expression levels of genes encoding enzymes of the flavonoid biosynthesis pathway (phenylalanine ammonialyase and chalcone synthase) were determined. A significant accumulation of total salicylic acid (TSA) and abscisic acid (ABA) was recorded in the roots and leaves of pea seedlings growing on lead-supplemented medium and next during infestation by aphids. Increased generation of these phytohormones strongly enhanced the biosynthesis of flavonoids, including a phytoalexin, pisatin. This research provides insights into the cross-talk between the abiotic (lead) and biotic factor (aphid infestation) on the level of the generation of signalling molecules and their role in the induction of flavonoid biosynthesis.

Fibronectin matrix assembly is essential for cell condensation during chondrogenesis

PubMed Central

Singh, Purva; Schwarzbauer, Jean E.

2014-01-01

ABSTRACT Mesenchymal cell condensation is the initiating event in endochondral bone formation. Cell condensation is followed by differentiation into chondrocytes, which is accompanied by induction of chondrogenic gene expression. Gene mutations involved in chondrogenesis cause chondrodysplasias and other skeletal defects. Using mesenchymal stem cells (MSCs) in an in vitro chondrogenesis assay, we found that knockdown of the diastrophic dysplasia (DTD) sulfate transporter (DTDST, also known as SLC26A2), which is required for normal cartilage development, blocked cell condensation and caused a significant reduction in fibronectin matrix. Knockdown of fibronectin with small interfering RNAs (siRNAs) also blocked condensation. Fibrillar fibronectin matrix was detected prior to cell condensation, and its levels increased during and after condensation. Inhibition of fibronectin matrix assembly by use of the functional upstream domain (FUD) of adhesin F1 from Streptococcus pyogenes prevented cell condensation by MSCs and also by the chondrogenic cell line ATDC5. Our data show that cell condensation and induction of chondrogenesis depend on fibronectin matrix assembly and DTDST, and indicate that this transporter is required earlier in chondrogenesis than previously appreciated. They also raise the possibility that certain of the skeletal defects in DTD patients might derive from the link between DTDST, fibronectin matrix and condensation. PMID:25146392

Fibronectin matrix assembly is essential for cell condensation during chondrogenesis.

PubMed

Singh, Purva; Schwarzbauer, Jean E

2014-10-15

Mesenchymal cell condensation is the initiating event in endochondral bone formation. Cell condensation is followed by differentiation into chondrocytes, which is accompanied by induction of chondrogenic gene expression. Gene mutations involved in chondrogenesis cause chondrodysplasias and other skeletal defects. Using mesenchymal stem cells (MSCs) in an in vitro chondrogenesis assay, we found that knockdown of the diastrophic dysplasia (DTD) sulfate transporter (DTDST, also known as SLC26A2), which is required for normal cartilage development, blocked cell condensation and caused a significant reduction in fibronectin matrix. Knockdown of fibronectin with small interfering RNAs (siRNAs) also blocked condensation. Fibrillar fibronectin matrix was detected prior to cell condensation, and its levels increased during and after condensation. Inhibition of fibronectin matrix assembly by use of the functional upstream domain (FUD) of adhesin F1 from Streptococcus pyogenes prevented cell condensation by MSCs and also by the chondrogenic cell line ATDC5. Our data show that cell condensation and induction of chondrogenesis depend on fibronectin matrix assembly and DTDST, and indicate that this transporter is required earlier in chondrogenesis than previously appreciated. They also raise the possibility that certain of the skeletal defects in DTD patients might derive from the link between DTDST, fibronectin matrix and condensation. © 2014. Published by The Company of Biologists Ltd.

Accelerated Blood Clearance (ABC) Phenomenon Favors the Accumulation of Tartar Emetic in Pegylated Liposomes in BALB/c Mice Liver.

PubMed

Lopes, Tamara C M; Silva, Débora F; Costa, Walyson C; Frézard, Frédéric; Barichello, José M; Silva-Barcellos, Neila M; de Lima, Wanderson G; Rezende, Simone A

2018-01-01

Tartar emetic (TE) was the first drug used to treat leishmaniasis. However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. This work evaluated the effect of TE administration on histopathological aspects and the effect of the ABC phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of ABC phenomenon with no toxicity to other organs.

Accelerated Blood Clearance (ABC) Phenomenon Favors the Accumulation of Tartar Emetic in Pegylated Liposomes in BALB/c Mice Liver

PubMed Central

Lopes, Tamara C. M.; Silva, Débora F.; Costa, Walyson C.; Barichello, José M.; Silva-Barcellos, Neila M.; de Lima, Wanderson G.

2018-01-01

Tartar emetic (TE) was the first drug used to treat leishmaniasis. However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. This work evaluated the effect of TE administration on histopathological aspects and the effect of the ABC phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of ABC phenomenon with no toxicity to other organs. PMID:29593857

Induced mutations in mice and genetic risk assessment in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Selby, P.B.

1980-01-01

In studies on mice, in contrast to studies on humans, it is possible to perform carefully controlled experiments with the exposures one desires. The necessity for having separate mammalian tests for looking at the induction of gene mutations and small deficiencies, and at the induction of chromosomal aberrations, is obvious. Mutagens can differ as to which of these types of damage they are more likely to cause. The reason for focusing attention on the mouse in a discussion of hazard from induced gene mutations and small deficiencies is the existence of techniques in this mammal for readily studying the inductionmore » of such genetic effects. Many mutations at the molecular level cause no apparent changes at the gene-product level and many mutations that cause changes at the gene-product level cause no detectable phenotypic changes in heterozygotes. Many dominant mutations that change the phenotype cause no serious handicap. For these reasons, risk estimation for important chemicals must rely heavily on studies on the induction of those germinal mutations in mammals that are easily related to human dominant disorders, such as skeletal and cataract mutations. Molecular or enzyme studies cannot provide definitive answers about risk. The specific-locus method should help greatly in assessing the genetic risks to humans from chemicals. The new sensitive-indicator method should complement it in providing a tool for attacking the question of what treatments induce gene mutations and small deficiencies and for approximating first-generation damage to the skeleton. (ERB)« less

Episodic specificity induction impacts activity in a core brain network during construction of imagined future experiences

PubMed Central

Madore, Kevin P.; Szpunar, Karl K.; Addis, Donna Rose; Schacter, Daniel L.

2016-01-01

Recent behavioral work suggests that an episodic specificity induction—brief training in recollecting the details of a past experience—enhances performance on subsequent tasks that rely on episodic retrieval, including imagining future experiences, solving open-ended problems, and thinking creatively. Despite these far-reaching behavioral effects, nothing is known about the neural processes impacted by an episodic specificity induction. Related neuroimaging work has linked episodic retrieval with a core network of brain regions that supports imagining future experiences. We tested the hypothesis that key structures in this network are influenced by the specificity induction. Participants received the specificity induction or one of two control inductions and then generated future events and semantic object comparisons during fMRI scanning. After receiving the specificity induction compared with the control, participants exhibited significantly more activity in several core network regions during the construction of imagined events over object comparisons, including the left anterior hippocampus, right inferior parietal lobule, right posterior cingulate cortex, and right ventral precuneus. Induction-related differences in the episodic detail of imagined events significantly modulated induction-related differences in the construction of imagined events in the left anterior hippocampus and right inferior parietal lobule. Resting-state functional connectivity analyses with hippocampal and inferior parietal lobule seed regions and the rest of the brain also revealed significantly stronger core network coupling following the specificity induction compared with the control. These findings provide evidence that an episodic specificity induction selectively targets episodic processes that are commonly linked to key core network regions, including the hippocampus. PMID:27601666

Protective Effect of Mangifera indica Linn., Cocos nucifera Linn., and Averrhoa carambola Linn. Extracts against Ultraviolet B-Induced Damage in Human Keratinocytes.

PubMed

Ronpirin, Chalinee; Pattarachotanant, Nattaporn; Tencomnao, Tewin

2016-01-01

This study was aimed at investigating the antioxidant activity of Mangifera indica Linn., Cocos nucifera Linn., and Averrhoa carambola Linn. and their biological effect on human keratinocytes affected by the ultraviolet B (UVB), a major cause of cell damage and skin cancer through induction of DNA damage, production of reactive oxygen species (ROS), and apoptosis. The richest antioxidant activity was found in ethanol fraction of M. indica (21.32 ± 0.66 mg QE/g dry weight), while the lowest one was found in aqueous fractions of M. indica and C. nucifera (1.76 ± 2.10 and 1.65 ± 0.38 mg QE/g dry weight, respectively). Ethanol and aqueous fractions of A. carambola (250 µg/mL) significantly reduced the number of apoptotic cells. The expression of cleaved caspase 3 in UVB-treated group was significantly greater than that in untreated group. Both fractions of A. carambola (50, 100, and 250 µg/mL) significantly decreased the expression of cleaved caspase 3. Regarding the induction of DNA repair, ethanol (100 and 250 µg/mL) and aqueous (50, 100 and 250 µg/mL) fractions of A. carambola significantly decreased the percentage of cyclobutane pyrimidine dimers (CPD). Taken together, our results suggest that both fractions of A. carambola may be potentially developed for dermal applications.

Organochlorine pesticide, endosulfan induced cellular and organismal response in Drosophila melanogaster.

PubMed

Sharma, Anurag; Mishra, M; Shukla, A K; Kumar, R; Abdin, M Z; Chowdhuri, D Kar

2012-06-30

The effect of endosulfan (0.02-2.0μgmL(-1)) to Drosophila melanogaster (Oregon R(+)) at the cellular and organismal levels was examined. Third instar larvae of D. melanogaster and the strains transgenic for hsp70, hsp83 and hsp26 were exposed to endosulfan through food for 12-48h to examine the heat shock proteins (hsps), reactive oxygen species (ROS) generation, anti-oxidant stress markers and xenobiotic metabolism enzymes. We observed a concentration- and time-dependent significant induction of only small hsps (hsp23>hsp22) in the exposed organism in concurrence with a significant induction of ROS generation, oxidative stress and xenobiotic metabolism markers. Sub-organismal response was to be propagated towards organismal response, i.e., delay in the emergence of flies and decreased locomotor behaviour. Organisms with diminished locomotion also exhibited significantly lowered acetylcholinesterase activity. A significant positive correlation observed among ROS generation and different cellular endpoints (small hsps, oxidative stress markers, cytochrome P450 activities) in the exposed organism indicate a modulatory role of ROS in endosulfan-mediated cellular toxicity. The study thus suggests that the adverse effects of endosulfan in exposed Drosophila are manifested both at cellular and organismal levels and recommends Drosophila as an alternative animal model for screening the risk caused by environmental chemicals. Copyright © 2012 Elsevier B.V. All rights reserved.

Mechanical Tension Increases CCN2/CTGF Expression and Proliferation in Gingival Fibroblasts via a TGFβ-Dependent Mechanism

PubMed Central

Guo, Fen; Carter, David E.; Leask, Andrew

2011-01-01

Unlike skin, oral gingival do not scar in response to tissue injury. Fibroblasts, the cell type responsible for connective tissue repair and scarring, are exposed to mechanical tension during normal and pathological conditions including wound healing and fibrogenesis. Understanding how human gingival fibroblasts respond to mechanical tension is likely to yield valuable insights not only into gingival function but also into the molecular basis of scarless repair. CCN2/connective tissue growth factor is potently induced in fibroblasts during tissue repair and fibrogenesis. We subjected gingival fibroblasts to cyclical strain (up to 72 hours) using the Flexercell system and showed that CCN2 mRNA and protein was induced by strain. Strain caused the rapid activation of latent TGFβ, in a fashion that was reduced by blebbistatin and FAK/src inhibition, and the induction of endothelin (ET-1) mRNA and protein expression. Strain did not cause induction of α-smooth muscle actin or collagen type I mRNAs (proteins promoting scarring); but induced a cohort of pro-proliferative mRNAs and cell proliferation. Compared to dermal fibroblasts, gingival fibroblasts showed reduced ability to respond to TGFβ by inducing fibrogenic mRNAs; addition of ET-1 rescued this phenotype. Pharmacological inhibition of the TGFβ type I (ALK5) receptor, the endothelin A/B receptors and FAK/src significantly reduced the induction of CCN2 and pro-proliferative mRNAs and cell proliferation. Controlling TGFβ, ET-1 and FAK/src activity may be useful in controlling responses to mechanical strain in the gingiva and may be of value in controlling fibroproliferative conditions such as gingival hyperplasia; controlling ET-1 may be of benefit in controlling scarring in response to injury in the skin. PMID:21611193

Differential modulation of P-glycoprotein expression and activity by non-nucleoside HIV-1 reverse transcriptase inhibitors in cell culture.

PubMed

Störmer, Elke; von Moltke, Lisa L; Perloff, Michael D; Greenblatt, David J

2002-07-01

This study investigated the effects of the non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTI) nevirapine (NVR), efavirenz (EFV), and delavirdine (DLV) on P-glycoprotein (P-gp) activity and expression to anticipate P-gp related drug-drug interactions associated with combination therapy. NNRTIs were evaluated as P-gp substrates by measuring differential transport across Caco-2 cell monolayers. Inhibition of P-gp mediated rhodaminel23 (Rh123) transport in Caco-2 cells was used to assess P-gp inhibition by NNRTIs. Induction of P-gp expression and activity in LS180V cells following 3-day exposure to NNRTIs was measured by western blot analysis and cellular Rh123 uptake, respectively. The NNRTIs showed no differential transport between the basolateral to apical and apical to basolateral direction. NNRTI transport in either direction was not affected by the P-gp inhibitor verapamil. DLV inhibited Rh123 transport, causing a reduction to 15% of control at 100 microM (IC50 = 30 microM). NVR caused a concentration-dependent induction of P-gp expression in LS180V cells resulting in a 3.5-fold increase in immunoreactive P-gp at 100 microM NVR. Induction attributable to EFV and DLV was quantitatively smaller. NVR significantly reduced cellular uptake of Rh123 into LS180V cells, indicating increased drug efflux due to induced P-gp activity; effects of EFV and DLV were smaller. Acute DLV treatment of LS180V cells previously induced with NVR or ritonavir did not reverse the decreased Rh123 cell accumulation. NNRTIs show differential effects on P-gp activity and expression in vitro. Clinical studies are required to elucidate the clinical importance of potential drug interactions.

Cytotoxicity and gene induction by some essential oils in the yeast Saccharomyces cerevisiae.

PubMed

Bakkali, F; Averbeck, S; Averbeck, D; Zhiri, A; Idaomar, M

2005-08-01

In order to get an insight into the possible genotoxicity of essential oils (EOs) used in traditional pharmacological applications we tested five different oils extracted from the medicinal plants Origanum compactum, Coriandrum sativum, Artemisia herba alba, Cinnamomum camphora (Ravintsara aromatica) and Helichrysum italicum (Calendula officinalis) for genotoxic effects using the yeast Saccharomyces cerevisiae. Clear cytotoxic effects were observed in the diploid yeast strain D7, with the cells being more sensitive to EOs in exponential than in stationary growth phase. The cytotoxicity decreased in the following order: Origanum compactum>Coriandrum sativum>Artemisia herba alba>Cinnamomum camphora>Helichrysum italicum. In the same order, all EOs, except that derived from Helichrysum italicum, clearly induced cytoplasmic petite mutations indicating damage to mitochondrial DNA. However, no nuclear genetic events such as point mutations or mitotic intragenic or intergenic recombination were induced. The capacity of EOs to induce nuclear DNA damage-responsive genes was tested using suitable Lac-Z fusion strains for RNR3 and RAD51, which are genes involved in DNA metabolism and DNA repair, respectively. At equitoxic doses, all EOs demonstrated significant gene induction, approximately the same as that caused by hydrogen peroxide, but much lower than that caused by methyl methanesulfonate (MMS). EOs affect mitochondrial structure and function and can stimulate the transcriptional expression of DNA damage-responsive genes. The induction of mitochondrial damage by EOs appears to be closely linked to overall cellular cytotoxicity and appears to mask the occurrence of nuclear genetic events. EO-induced cytotoxicity involves oxidative stress, as is evident from the protection observed in the presence of ROS inhibitors such as glutathione, catalase or the iron-chelating agent deferoxamine.

Nasal and skin delivery of IC31(®)-adjuvanted recombinant HSV-2 gD protein confers protection against genital herpes.

PubMed

Wizel, Benjamin; Persson, Josefine; Thörn, Karolina; Nagy, Eszter; Harandi, Ali M

2012-06-19

Genital herpes caused by herpes simplex virus type 2 (HSV-2) remains the leading cause of genital ulcers worldwide. Given the disappointing results of the recent genital herpes vaccine trials in humans, development of novel vaccine strategies capable of eliciting protective mucosal and systemic immune responses to HSV-2 is urgently required. Here we tested the ability of the adjuvant IC31(®) in combination with HSV-2 glycoprotein D (gD) used through intranasal (i.n.), intradermal (i.d.), or subcutaneous (s.c.) immunization routes for induction of protective immunity against genital herpes infection in C57BL/6 mice. Immunization with gD plus IC31(®) through all three routes of immunization developed elevated gD-specific serum antibody responses with HSV-2 neutralizing activity. Whereas the skin routes promoted the induction of a mixed IgG2c/IgG1 isotype profile, the i.n. route only elicited IgG1 antibodies. All immunization routes were able to induce gD-specific IgG antibody responses in the vaginas of mice immunized with IC31(®)-adjuvanted gD. Although specific lymphoproliferative responses were observed in splenocytes from mice of most groups vaccinated with IC31(®)-adjuvanted gD, only i.d. immunization resulted in a significant splenic IFN-γ response. Further, immunization with gD plus IC31(®) conferred 80-100% protection against an otherwise lethal vaginal HSV-2 challenge with amelioration of viral replication and disease severity in the vagina. These results warrant further exploration of IC31(®) for induction of protective immunity against genital herpes and other sexually transmitted infections. Copyright © 2012 Elsevier Ltd. All rights reserved.

Conscious/Unconscious Dissociation Induction: Increasing Hypnotic Performance With "Resistant" Clients.

PubMed

Lankton, Stephen

2016-10-01

Milton H. Erickson promoted several approaches to psychotherapy using hypnosis. In the last decades of his life, his work moved away from the use of redundant suggestion and a predominance of direct suggestion in favor of indirect suggestion. In addition, he frequently employed a type of storytelling (that has come to be called therapeutic metaphor) to indirectly convey learning. Another change that occurred during the last decade was his definition of the cause of a symptom. However, there were two important areas of his work that he did not change during his career. These two components of his work he did not change were his definition of a cure and the importance of a naturalistic induction. This article concerns his naturalistic approach to hypnotic induction and especially his use of conscious/unconscious dissociation in the induction process and how indirect suggestion and therapeutic binds can be used to facilitate that type of induction and a cure.

Emittance Growth in the DARHT-II Linear Induction Accelerator

NASA Astrophysics Data System (ADS)

Ekdahl, Carl; Carlson, Carl A.; Frayer, Daniel K.; McCuistian, B. Trent; Mostrom, Christopher B.; Schulze, Martin E.; Thoma, Carsten H.

2017-11-01

The Dual-Axis Radiographic Hydrotest (DARHT) facility uses bremsstrahlung radiation source spots produced by the focused electron beams from two linear induction accelerators (LIAs) to radiograph large hydrodynamic experiments driven by high explosives. Radiographic resolution is determined by the size of the source spot, and beam emittance is the ultimate limitation to spot size. Some of the possible causes for the emittance growth in the DARHT LIA have been investigated using particle-in-cell (PIC) codes, and are discussed in this article. The results suggest that the most likely source of emittance growth is a mismatch of the beam to the magnetic transport, which can cause beam halo.

Ultraviolet-induced sister chromatid exchanges in V-79 cells with normal and BrdUrd-substituted DNA and the influence of intercalating substances and cysteine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Speit, G.; Mehnert, K.; Wolf, M.

1982-06-01

The influence of intercalating substances (proflavine, ethidium bromide) and of an SH compound (L-cysteine) on uv-induced sister chromatid exchanges (SCEs) was investigated in V-79 cells with normal and BrdUrd-substituted DNA. The results are discussed in relation to the primary damages leading to SCE induction produced by uv irradiation. The data indicate that neither the pyrimidine dimers nor DNA single-strand breaks are the primary cause of SCE induction, and that the damages leading to SCEs by uv irradiation differ from those which cause chromosome aberrations.

Variable frequency inverter for ac induction motors with torque, speed and braking control

NASA Technical Reports Server (NTRS)

Nola, F. J. (Inventor)

1975-01-01

A variable frequency inverter was designed for driving an ac induction motor which varies the frequency and voltage to the motor windings in response to varying torque requirements for the motor so that the applied voltage amplitude and frequency are of optimal value for any motor load and speed requirement. The slip frequency of the motor is caused to vary proportionally to the torque and feedback is provided so that the most efficient operating voltage is applied to the motor. Winding current surge is limited and a controlled negative slip causes motor braking and return of load energy to a dc power source.

Comparative Study of Oral and Vaginal Misoprostol for Induction of Labour, Maternal and Foetal Outcome

PubMed Central

Komala, Kambhampati; Reddy, Meherlatha; Quadri, Iqbal Jehan; B., Suneetha; V., Ramya

2013-01-01

Background: Misoprostol is a new promising agent for cervical ripening and induction of labour .The ideal dose, route and frequency of administration of misoprostol are still under investigation. Although, vaginal application of misoprostol has been validated as a reasonable mean of induction, there is a patient resistance to digital examination and there is a risk of ascending infection. For this reason, oral administration of misoprostol for cervical ripening and labour induction has been tried. Aims and Objectives: To compare 50μg of oral misoprostol versus 25μg of intravaginal misoprostol for induction of labour at term and maternal, foetal outcomes. Methods: Two hundred women who were at term, with indication for induction of labour and Bishop scores of ≤5 were randomly assigned to receive misoprostol 50μg or 25μg intravaginal, every 4-6 hours, for a maximum of 5 doses. In either group, pregnant females with inadequate uterine contractions despite being given maximum 5 doses of misoprostol, were augmented using oxytocin. The primary outcome measure was time-interval from induction to vaginal delivery and vaginal delivery rate within 24 hours. Results: The median induction to vaginal delivery time in oral group (12.92h) and vaginal group (14.04 h) was not significant. Oral misoprostol resulted in more number of vaginal deliveries as compared to vaginal misoprostol (94% as compared to 86%), which was not significant. There was a significantly higher incidence of uterine tachysystole in the vaginal group, as compared to oral group. There were no significant differences between the groups with respect to oxytocin augmentation, caesarean section rate, analgesic requirement and neonatal outcome. Conclusion: Oral misoprostol is as efficacious as vaginal misoprostol because of shorter induction delivery interval, lower caesarean section rates, and lower incidence of failed induction rates. Lower incidence of foetal distress and easy intake are observed if the drug is administered orally. PMID:24551660

Toll-like receptor 2-independent host innate immune response against an epidemic strain of Streptococcus suis that causes a toxic shock-like syndrome in humans.

PubMed

Lachance, Claude; Segura, Mariela; Gerber, Pehuén Pereyra; Xu, Jianguo; Gottschalk, Marcelo

2013-01-01

Streptococcus suis is an emerging zoonotic agent causing meningitis and septicemia. Outbreaks in humans in China with atypical cases of streptococcal toxic shock-like syndrome have been described to be caused by a clonal epidemic S. suis strain characterized as sequence type (ST) 7 by multilocus sequence typing, different from the classical ST1 usually isolated in Europe. Previous in vitro studies showed that Toll-like receptor (TLR) 2 plays a major role in S. suis ST1 interactions with host cells. In the present study, the in vivo role of TLR2 in systemic infections caused by S. suis ST1 or ST7 strains using TLR2 deficient (TLR2(-/-)) mice was evaluated. TLR2-mediated recognition significantly contributes to the acute disease caused by the highly virulent S. suis ST1 strain, since the TLR2(-/-) mice remained unaffected when compared to wild type (WT) mice. The lack of mortality could not be associated with a lower bacterial burden; however, a significant decrease in the induction of pro-inflammatory mediators, as evaluated by microarray, real-time PCR and protein assays, was observed. On the other hand, TLR2(-/-) mice infected with the epidemic ST7 strain presented no significant differences regarding survival and expression of pro-inflammatory mediators when compared to the WT mice. Together, these results show a TLR2-independent host innate immune response to S. suis that depends on the strain.

Effect of airway clearance techniques on the efficacy of the sputum induction procedure.

PubMed

Elkins, M R; Lane, T; Goldberg, H; Pagliuso, J; Garske, L A; Hector, E; Marchetto, L; Alison, J A; Bye, P T P

2005-11-01

Sputum induction is used in the early identification of tuberculosis (TB) and pneumocystis infections of the lung. Although manual physiotherapy techniques to clear the airways are often incorporated in the sputum induction procedure, their efficacy in this setting is unknown. This randomised, crossover trial enrolled adults referred for sputum induction for suspected TB and pneumocystis infections of the lung. All participants underwent two sputum induction procedures, inhaling 3% saline via ultrasonic nebuliser. During one randomly allocated procedure, airway clearance techniques (chest wall percussion, vibration, huffing) were incorporated. In total, 59 participants completed the trial. The airway clearance techniques had no significant effect on how the test was tolerated, the volume expectorated or the quality of the sample obtained (assessed by the presence of alveolar macrophages). The techniques did not significantly affect how often the test identified a suspected organism, nor the sensitivity or specificity of sputum induction. In conclusion, the study was unable to demonstrate any effect of airway clearance techniques on the sputum induction procedure. The results provide some justification for not including airway clearance techniques as part of the sputum induction procedure.

Non-response to sad mood induction: implications for emotion research.

PubMed

Rottenberg, Jonathan; Kovacs, Maria; Yaroslavsky, Ilya

2018-05-01

Experimental induction of sad mood states is a mainstay of laboratory research on affect and cognition, mood regulation, and mood disorders. Typically, the success of such mood manipulations is reported as a statistically significant pre- to post-induction change in the self-rated intensity of the target affect. The present commentary was motivated by an unexpected finding in one of our studies concerning the response rate to a well-validated sad mood induction. Using the customary statistical approach, we found a significant mean increase in self-rated sadness intensity with a moderate effect size, verifying the "success" of the mood induction. However, that "success" masked that, between one-fifth and about one-third of our samples (adolescents who had histories of childhood-onset major depressive disorder and healthy controls) reported absolutely no sadness in response to the mood induction procedure. We consider implications of our experience for emotion research by (1) commenting upon the typically overlooked phenomenon of nonresponse, (2) suggesting changes in reporting practices regarding mood induction success, and (3) outlining future directions to help scientists determine why some subjects do not respond to experimental mood induction.

The effects of tramadol on postoperative shivering after sevoflurane and remifentanil anesthesia.

PubMed

Nakagawa, Taku; Hashimoto, Miki; Hashimoto, Yasunori; Shirozu, Kazuhiro; Hoka, Sumio

2017-01-03

Remifentanil has been reported to cause post-anesthetic shivering (PAS). Higher doses of remifentanil reportedly induce more intense PAS. Tramadol, a synthetic opioid that acts at multiple sites, is considered to be an effective treatment for PAS, but the evidence for its therapeutic benefit after remifentanil anesthesia is limited. We investigated the effect of tramadol on the incidence of PAS after remifentanil anesthesia. Sixty-three patients who had undergone upper abdominal surgery under general anesthesia were studied retrospectively. Tramadol was administered at induction of anesthesia. The patients were divided into four groups: HT(+), high dose remifentanil (1-1.5 μg/kg/min) with tramadol; HT(-), high dose remifentanil without tramadol; LT(+), low dose remifentanil (0.15-0.25 μg/kg/min) with tramadol; and LT(-), low dose remifentanil without tramadol. We recorded perioperative changes in nasopharyngeal temperature and episodes of PAS on emergence from anesthesia. The incidences of PAS in both tramadol treatment groups were significantly lower than the groups that did not receive tramadol. Nasopharyngeal temperature after surgery fell significantly more from baseline in the tramadol treatment groups compared with the non-treatment groups. Tramadol administered at induction of anesthesia appears to suppress PAS following remifentanil anesthesia.

Tick-Borne Encephalitis Virus Nonstructural Protein NS5 Induces RANTES Expression Dependent on the RNA-Dependent RNA Polymerase Activity.

PubMed

Zheng, Zifeng; Yang, Jieyu; Jiang, Xuan; Liu, Yalan; Zhang, Xiaowei; Li, Mei; Zhang, Mudan; Fu, Ming; Hu, Kai; Wang, Hanzhong; Luo, Min-Hua; Gong, Peng; Hu, Qinxue

2018-05-14

Tick-borne encephalitis virus (TBEV) is one of the flaviviruses that targets the CNS and causes encephalitis in humans. The mechanism of TBEV that causes CNS destruction remains unclear. It has been reported that RANTES-mediated migration of human blood monocytes and T lymphocytes is specifically induced in the brain of mice infected with TBEV, which causes ensuing neuroinflammation and may contribute to brain destruction. However, the viral components responsible for RANTES induction and the underlying mechanisms remain to be fully addressed. In this study, we demonstrate that the NS5, but not other viral proteins of TBEV, induces RANTES production in human glioblastoma cell lines and primary astrocytes. TBEV NS5 appears to activate the IFN regulatory factor 3 (IRF-3) signaling pathway in a manner dependent on RIG-I/MDA5, which leads to the nuclear translocation of IRF-3 to bind with RANTES promoter. Further studies reveal that the activity of RNA-dependent RNA polymerase (RdRP) but not the RNA cap methyltransferase is critical for TBEV NS5-induced RANTES expression, and this is likely due to RdRP-mediated synthesis of dsRNA. Additional data indicate that the residues at K359, D361, and D664 of TBEV NS5 are critical for RdRP activity and RANTES induction. Of note, NS5s from other flaviviruses, including Japanese encephalitis virus, West Nile virus, Zika virus, and dengue virus, can also induce RANTES expression, suggesting the significance of NS5-induced RANTES expression in flavivirus pathogenesis. Our findings provide a foundation for further understanding how flaviviruses cause neuroinflammation and a potential viral target for intervention. Copyright © 2018 by The American Association of Immunologists, Inc.

Gamma-interferon causes a selective induction of the lysosomal proteases, cathepsins B and L, in macrophages

NASA Technical Reports Server (NTRS)

Lah, T. T.; Hawley, M.; Rock, K. L.; Goldberg, A. L.

1995-01-01

Previous studies have indicated that acid-optimal cysteine proteinase(s) in the endosomal-lysosomal compartments, cathepsins, play a critical role in the proteolytic processing of endocytosed proteins to generate the antigenic peptides presented to the immune system on major histocompatibility complex (MHC) class II molecules. The presentation of these peptides and the expression of MHC class II molecules by macrophages and lymphocytes are stimulated by gamma-interferon (gamma-IFN). We found that treatment of human U-937 monocytes with gamma-IFN increased the activities and the content of the two major lysosomal cysteine proteinases, cathepsins B and L. Assays of protease activity, enzyme-linked immunosorbant assays (ELISA) and immunoblotting showed that this cytokine increased the amount of cathepsin B 5-fold and cathepsin L 3-fold in the lysosomal fraction. By contrast, the aspartic proteinase, cathepsin D, in this fraction was not significantly altered by gamma-IFN treatment. An induction of cathepsins B and L was also observed in mouse macrophages, but not in HeLa cells. These results suggest coordinate regulation in monocytes of the expression of cathepsins B and L and MHC class II molecules. Presumably, this induction of cysteine proteases contributes to the enhancement of antigen presentation by gamma-IFN.

Mammalian transcription factor LSF is a target of ERK signaling

PubMed Central

Pagon, Zrinka; Volker, Janet; Cooper, Geoffrey M.; Hansen, Ulla

2012-01-01

LSF is a mammalian transcription factor that is rapidly and quantitatively phosphorylated upon growth induction of resting, peripheral human T cells, as assayed by a reduction in its electrophoretic mobility. The DNA-binding activity of LSF in primary T cells is greatly increased after this phosphorylation event [Volker et al., 1997]. We demonstrate here that LSF is also rapidly and quantitatively phosphorylated upon growth induction in NIH 3T3 cells, although its DNA-binding activity is not significantly altered. Three lines of experimentation established that ERK is responsible for phosphorylating LSF upon growth induction in both cell types. First, phosphorylation of LSF by ERK is sufficient to cause the reduced electrophoretic mobility of LSF. Second, the amount of ERK activity correlates with the extent of LSF phosphorylation in both primary human T cells and NIH 3T3 cells. Finally, specific inhibitors of the Ras/Raf/MEK/ERK pathway inhibit LSF modification in vivo. This phosphorylation by ERK is not sufficient for activation of LSF DNA-binding activity, as evidenced both in vitro and in mouse fibroblasts. Nonetheless, activation of ERK is a prerequisite for the substantial increase in LSF DNA-binding activity upon activation of resting T cells, indicating that ERK phosphorylation is necessary but not sufficient for activation of LSF in this cell type. PMID:12858339

Interferon-γ-Induced Unfolded Protein Response in Conjunctival Goblet Cells as a Cause of Mucin Deficiency in Sjögren Syndrome.

PubMed

Coursey, Terry G; Tukler Henriksson, Johanna; Barbosa, Flavia L; de Paiva, Cintia S; Pflugfelder, Stephen C

2016-06-01

Goblet cells (GCs) are specialized secretory cells that produce mucins and a variety of other proteins. Significant conjunctival GC loss occurs in both experimental dry eye models and patients with keratoconjunctivitis sicca due to the induction of interferon (IFN)-γ. With the use of a primary murine culture model, we found that GCs are highly sensitive to IFN-γ with significantly reduced proliferation and altered structure with low concentrations. GC cultures treated with IFN-γ have increased gene expression of Muc2 and Muc5AC but do not express these mucin glycoproteins. We hypothesized that IFN-γ induces endoplasmic reticulum stress and the unfolded protein response (UPR) in GCs. Cultures treated with IFN-γ increased expression of UPR-associated genes and proteins. Increased GRP78 and sXBP1 expression was found in experimental dry eye and Sjögren syndrome models and was GC specific. Increased GRP78 was also found in the conjunctiva of patients with Sjögren syndrome at the gene and protein levels. Treatment with dexamethasone inhibited expression of UPR-associated genes and increased mucin production. These results indicate that induction of UPR by IFN-γ is an important cause of GC-associated mucin deficiency observed in aqueous-deficient dry eye. Therapies to block the effects of IFN-γ on the metabolically active endoplasmic reticulum in these cells might enhance synthesis and secretion of the protective GC mucins on the ocular surface. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Effects of titanium dioxide (TiO2 ) nanoparticles on caribbean reef-building coral (Montastraea faveolata).

PubMed

Jovanović, Boris; Guzmán, Héctor M

2014-06-01

Increased use of manufactured titanium dioxide nanoparticles (nano-TiO2 ) is causing a rise in their concentration in the aquatic environment, including coral reef ecosystems. Caribbean mountainous star coral (Montastraea faveolata) has frequently been used as a model species to study gene expression during stress and bleaching events. Specimens of M. faveolata were collected in Panama and exposed for 17 d to nano-TiO2 suspensions (0.1 mg L(-1) and 10 mg L(-1) ). Exposure to nano-TiO2 caused significant zooxanthellae expulsion in all the colonies, without mortality. Induction of the gene for heat-shock protein 70 (HSP70) was observed during an early stage of exposure (day 2), indicating acute stress. However, there was no statistical difference in HSP70 expression on day 7 or 17, indicating possible coral acclimation and recovery from stress. No other genes were significantly upregulated. Inductively coupled plasma mass spectrometry analysis revealed that nano-TiO2 was predominantly trapped and stored within the posterior layer of the coral fragment (burrowing sponges, bacterial and fungal mats). The bioconcentration factor in the posterior layer was close to 600 after exposure to 10 mg L(-1) of nano-TiO2 for 17 d. The transient increase in HSP70, expulsion of zooxanthellae, and bioaccumulation of nano-TiO2 in the microflora of the coral colony indicate the potential of such exposure to induce stress and possibly contribute to an overall decrease in coral populations. © 2014 SETAC.

LED-activated pheophorbide a in ovarian cancer cells: Cytotoxicity and apoptosis induction

NASA Astrophysics Data System (ADS)

Liu, L.; Xu, C. S.; Xia, X. S.; Leung, A. W. N.

2011-02-01

Pheophorbide a (Pa) from Chinese herbal medicine Scutellaria Barbata and Silkworm excreta has been proved to be potential photosensitizer. The present study investigated the cytotoxicity of ovarian cancer cells induced by LED-activated Pa using light microscopy with the SRB staining. We further investigated the apoptosis of the cells 6 h after LED-activated Pa using of the flow cytometer with PI staining and nuclear staining. The results showed that LED-activated Pa remarkably caused cell death of ovarian cancer cells. The condensation of chromatin, nuclear fragmentations, and 12.3% of cells containing subdiploid levels of DNA were found in the ovarian cancer cells after the treatment of LED-activated Pa. These data demonstrated that LED-activated Pa could cause significant cytotoxicity and apoptosis of ovarian cancer cells.

Practical Design Guidelines of qZSI Based Step-Up DC/DC Converter

NASA Astrophysics Data System (ADS)

Zakis, Janis; Vinnikov, Dmitri; Roasto, Indrek; Jalakas, Tanel

2010-01-01

This paper presents some design guidelines for a new voltage fed step-up DC/DC isolated converter. The most significant advantage of proposed converter is voltage buck-boost operation on single stage. The most promising application for proposed converter is in the field of distributed power generation e.g. fuel cells or photovoltaic. The most sensitive issues - such as power losses caused by high currents in the input side of converter and high transient overvoltages across the inverter bridge caused by stray inductances were discussed and solved. The proposals and recommendations to overcome these issues are given in the paper. The Selection and design guidelines of converter elements are proposed and explained. The prototype of proposed converter was built and experimentally tested. Some results are presented and evaluated.

Activation of cathepsins B and L in mouse lymphosarcoma tissue under the effect of cyclophosphamide is associated with apoptosis induction and infiltration by mononuclear phagocytes.

PubMed

Zhanaeva, S Ya; Mel'nikova, E V; Trufakin, V A; Korolenko, T A

2013-11-01

We analyzed activities of lysosomal cystein cathepsins B and L in mouse LS lymphosarcoma and its drug-resistant RLS 40 strain and their correlations with the dynamics of the percentage of cells with fragmented DNA and CD14 (+) phagocytes over 3 days after cyclophosphamide injection. LS regression and inhibition of RLS 40 growth after cyclophosphamide injection were paralleled by an increase in cathepsins B and L activities in tumor tissues. The antitumor effect of cyclophosphamide associated with apoptosis intensity and protease activities were significantly higher in LS. Positive correlations between activities of cathepsins B and L and the LS tissue content of cells with fragmented DNA and CD14 (+) phagocytes and negative correlations thereof with tumor weight were detected. It seems that the increase in cathepsins B and L activities in LS tissues was caused by cyclophosphamide induction of apoptosis and depended on the level of tumor cell infiltration with mononuclear phagocytes.

Brown adipose tissue responds to cold and adrenergic stimulation by induction of FGF21.

PubMed

Chartoumpekis, Dionysios V; Habeos, Ioannis G; Ziros, Panos G; Psyrogiannis, Agathoklis I; Kyriazopoulou, Venetsana E; Papavassiliou, Athanasios G

2011-01-01

Fibroblast growth factor-21 (FGF21) is a pleiotropic protein involved in glucose, lipid metabolism and energy homeostasis, with main tissues of expression being the liver and adipose tissue. Brown adipose tissue (BAT) is responsible for cold-induced thermogenesis in rodents. The role of FGF21 in BAT biology has not been investigated. In the present study, wild-type C57BL/6J mice as well as a brown adipocyte cell line were used to explore the potential role of cold exposure and β3-adrenergic stimulation in the expression of FGF21 in BAT. Our results demonstrate that short-term exposure to cold, as well as β3-adrenergic stimulation, causes a significant induction of FGF21 mRNA levels in BAT, without a concomitant increase in FGF21 plasma levels. This finding opens new routes for the potential use of pharmaceuticals that could induce FGF21 and, hence, activate BAT thermogenesis.

Evodiamine Induces Cell Growth Arrest, Apoptosis and Suppresses Tumorigenesis in Human Urothelial Cell Carcinoma Cells.

PubMed

Shi, Chung-Sheng; Li, Jhy-Ming; Chin, Chih-Chien; Kuo, Yi-Hung; Lee, Ying-Ray; Huang, Yun-Ching

2017-03-01

Evodiamine, an indole alkaloid derived from Evodia rutaecarpa, exhibits pharmacological activities including vasodilatation, analgesia, anti-cardiovascular disease, anti-Alzheimer's disease, anti-inflammation, and anti-tumor activity. This study analyzes the anti-tumor effects of evodiamine on cellular growth, tumorigenesis, cell cycle and apoptosis induction of human urothelial cell carcinoma (UCC) cells. The present study showed that evodiamine significantly inhibited the proliferation of UCC cells in a dose- and time-dependent manner. Also, evodiamine suppressed the tumorigenesis of UCC cells in vitro. Moreover, evodiamine caused G 2 /M cell-cycle arrest and induced caspase-dependent apoptosis in UCC cells. Finally, we demonstrated that evodiamine exhibits better cytotoxic than 5-fluorouracil, a clinical chemotherapeutic drug, for UCC cells. Evodiamine induces growth inhibition, tumorigenesis suppression, cell-cycle arrest, and apoptosis induction in human UCC cells. Therefore, this agent displays a therapeutic potential for treating human UCC cells and is worthy for further investigation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

CARD9-Dependent Neutrophil Recruitment Protects against Fungal Invasion of the Central Nervous System

PubMed Central

Swamydas, Muthulekha; Rodriguez, Carlos A.; Lim, Jean K.; Mendez, Laura M.; Fink, Danielle L.; Hsu, Amy P.; Zhai, Bing; Karauzum, Hatice; Mikelis, Constantinos M.; Rose, Stacey R.; Ferre, Elise M. N.; Yockey, Lynne; Lemberg, Kimberly; Kuehn, Hye Sun; Rosenzweig, Sergio D.; Lin, Xin; Chittiboina, Prashant; Datta, Sandip K.; Belhorn, Thomas H.; Weimer, Eric T.; Hernandez, Michelle L.; Hohl, Tobias M.; Kuhns, Douglas B.; Lionakis, Michail S.

2015-01-01

Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9 -/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9 -/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans. PMID:26679537

Spatial distribution and historical trends of heavy metals in the sediments of petroleum producing regions of the Beibu Gulf, China.

PubMed

Yang, Jichao; Wang, Weiguo; Zhao, Mengwei; Chen, Bin; Dada, Olusegun A; Chu, Zhihui

2015-02-15

The concentrations of As, Sb, Hg, Pb, Cd, and Ba in the surface and core sediments of the oil and gas producing region of the Beibu Gulf were measured by Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Atomic Fluorescence Spectrometry (AFS), and the spatial distribution and historical trends of these elements are discussed. The results show that the concentrations of these elements are highest near the platforms. The results of Enrichment Factor (EF) and Potential Ecological Risk Index (PERI) also reveal significantly higher enrichment around the platforms, which imply that the offshore petroleum production was the cause of the unusual distribution and severe enrichment of these elements in the study area. The environment around the platforms was highly laden with toxic elements, thereby representing a very high ecological risk to the environment of the study area. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fast wave direct electron heating in advanced inductive and ITER baseline scenario discharges in DIII-D

DOE PAGES

Pinsker, R. I.; Austin, M. E.; Diem, S. J.; ...

2014-02-12

Fast Wave (FW) heating and electron cyclotron heating (ECH) are used in the DIII-D tokamak to study plasmas with low applied torque and dominant electron heating characteristic of burning plasmas. FW heating via direct electron damping has reached the 2.5 MW level in high performance ELMy H-mode plasmas. In Advanced Inductive (AI) plasmas, core FW heating was found to be comparable to that of ECH, consistent with the excellent first-pass absorption of FWs predicted by ray-tracing models at high electron beta. FW heating at the ~2 MW level to ELMy H-mode discharges in the ITER Baseline Scenario (IBS) showed unexpectedlymore » strong absorption of FW power by injected neutral beam (NB) ions, indicated by significant enhancement of the D-D neutron rate, while the intended absorption on core electrons appeared rather weak. As a result, the AI and IBS discharges are compared in an effort to identify the causes of the different response to FWs.« less

Fast wave direct electron heating in advanced inductive and ITER baseline scenario discharges in DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinsker, R. I.; Jackson, G. L.; Luce, T. C.

Fast Wave (FW) heating and electron cyclotron heating (ECH) are used in the DIII-D tokamak to study plasmas with low applied torque and dominant electron heating characteristic of burning plasmas. FW heating via direct electron damping has reached the 2.5 MW level in high performance ELMy H-mode plasmas. In Advanced Inductive (AI) plasmas, core FW heating was found to be comparable to that of ECH, consistent with the excellent first-pass absorption of FWs predicted by ray-tracing models at high electron beta. FW heating at the ∼2 MW level to ELMy H-mode discharges in the ITER Baseline Scenario (IBS) showed unexpectedlymore » strong absorption of FW power by injected neutral beam (NB) ions, indicated by significant enhancement of the D-D neutron rate, while the intended absorption on core electrons appeared rather weak. The AI and IBS discharges are compared in an effort to identify the causes of the different response to FWs.« less

Fast wave direct electron heating in advanced inductive and ITER baseline scenario discharges in DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinsker, R. I.; Austin, M. E.; Diem, S. J.

Fast Wave (FW) heating and electron cyclotron heating (ECH) are used in the DIII-D tokamak to study plasmas with low applied torque and dominant electron heating characteristic of burning plasmas. FW heating via direct electron damping has reached the 2.5 MW level in high performance ELMy H-mode plasmas. In Advanced Inductive (AI) plasmas, core FW heating was found to be comparable to that of ECH, consistent with the excellent first-pass absorption of FWs predicted by ray-tracing models at high electron beta. FW heating at the ~2 MW level to ELMy H-mode discharges in the ITER Baseline Scenario (IBS) showed unexpectedlymore » strong absorption of FW power by injected neutral beam (NB) ions, indicated by significant enhancement of the D-D neutron rate, while the intended absorption on core electrons appeared rather weak. As a result, the AI and IBS discharges are compared in an effort to identify the causes of the different response to FWs.« less

Astrocyte-neuron lactate transport is required for long-term memory formation

PubMed Central

Suzuki, Akinobu; Stern, Sarah A.; Bozdagi, Ozlem; Huntley, George W.; Walker, Ruth H.; Magistretti, Pierre J.; Alberini, Cristina M.

2011-01-01

SUMMARY We report that in the rat hippocampus learning leads to a significant increase in extracellular lactate levels, which derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in-vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation. PMID:21376239

Effects of brief mindful acceptance induction on implicit dysfunctional attitudes and concordance between implicit and explicit dysfunctional attitudes.

PubMed

Keng, Shian-Ling; Seah, Stanley T H; Tong, Eddie M W; Smoski, Moria

2016-08-01

Mindfulness-based interventions have been shown to be effective in alleviating depressive symptoms. While much work has examined the effects of mindfulness training on subjective symptoms and experiences, and less is known regarding whether mindfulness training may alter relatively uncontrollable cognitive processes associated with depressed mood, particularly implicit dysfunctional attitudes. The present study examined the effects of a brief mindful acceptance induction on implicit dysfunctional attitudes and degree of concordance between implicit and explicit dysfunctional attitudes in the context of sad mood. A total of 79 adult participants with elevated depressive symptoms underwent an autobiographical mood induction procedure before being randomly assigned to mindful acceptance or thought wandering inductions. Results showed that the effect of mindful acceptance on implicit dysfunctional attitude was significantly moderated by trait mindfulness. Participants high on trait mindfulness demonstrated significant improvements in implicit dysfunctional attitudes following the mindful acceptance induction. Those low on trait mindfulness demonstrated significantly worse implicit dysfunctional attitudes following the induction. Significantly greater levels of concordance between implicit and explicit dysfunctional attitudes were observed in the mindful acceptance condition versus the thought wandering condition. The findings highlight changes in implicit dysfunctional attitudes and improvements in self-concordance as two potential mechanisms underlying the effects of mindfulness-based interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bayes and blickets: Effects of knowledge on causal induction in children and adults

PubMed Central

Griffiths, Thomas L.; Sobel, David M.; Tenenbaum, Joshua B.; Gopnik, Alison

2011-01-01

People are adept at inferring novel causal relations, even from only a few observations. Prior knowledge about the probability of encountering causal relations of various types and the nature of the mechanisms relating causes and effects plays a crucial role in these inferences. We test a formal account of how this knowledge can be used and acquired, based on analyzing causal induction as Bayesian inference. Five studies explored the predictions of this account with adults and 4-year-olds, using tasks in which participants learned about the causal properties of a set of objects. The studies varied the two factors that our Bayesian approach predicted should be relevant to causal induction: the prior probability with which causal relations exist, and the assumption of a deterministic or a probabilistic relation between cause and effect. Adults’ judgments (Experiments 1, 2, and 4) were in close correspondence with the quantitative predictions of the model, and children’s judgments (Experiments 3 and 5) agreed qualitatively with this account. PMID:21972897

DNA strand breaks signal the induction of DNA double-strand break repair in Saccharomyces cerevisiae.

PubMed

Singh, Rakesh Kumar; Krishna, Malini

2005-12-01

Genotoxic stress induces a checkpoint signaling cascade to generate a stress response. Saccharomyces cerevisiae shows an altered radiation response under different type of stress. Although the induction of repair has been implicated in enhanced survival after exposure to the challenging stress, the nature of the signal remains poorly understood. This study demonstrates that low doses of gamma radiation and bleomycin induce RAD52-dependent recombination repair pathway in the wild-type strain D-261. Prior exposure of cells to DNA-damaging agents (gamma radiation or bleomycin) equips them better for the subsequent damage caused by challenging doses. However, exposure to UV light, which does not cause strand breaks, was ineffective. This was confirmed by PFGE studies. This indicates that the strand breaks probably serve as the signal for induction of the recombination repair pathway while pyrimidine dimers do not. The nature of the induced repair was investigated by mutation scoring in special strain D-7, which showed that the induced repair is essentially error free.

Critical role of mast cells and peroxisome proliferator-activated receptor gamma (PPARγ) in the induction of myeloid-derived suppressor cells by marijuana cannabidiol in vivo

PubMed Central

Hegde, Venkatesh L.; Singh, Udai P.; Nagarkatti, Prakash S.; Nagarkatti, Mitzi

2015-01-01

Cannabidiol (CBD) is a natural non-psychotropic cannabinoid from marijuana (Cannabis sativa) with anti-epileptic and anti-inflammatory properties. Effect of CBD on naïve immune system is not precisely understood. In this study, we observed that administering CBD into naïve mice triggers robust induction of CD11b+Gr-1+ MDSC in the peritoneum, which expressed functional Arg1, and potently suppressed T cell proliferation ex vivo. Further, CBD-MDSC suppressed LPS-induced acute inflammatory response upon adoptive transfer in vivo. CBD-induced suppressor cells were comprised of CD11b+Ly6-G+Ly6-C+ granulocytic and CD11b+Ly6-G−Ly6-C+ monocytic subtypes, with monocytic MDSC exhibiting higher T cell suppressive function. Induction of MDSC by CBD was markedly attenuated in Kit-mutant (KitW/W-v) mast cell-deficient mice. MDSC response was reconstituted upon transfer of WT bone marrow-derived mast cells in KitW/W-v mice suggesting the key role of cKit (CD117) as well as mast cells. Moreover, mast cell activator compound 48/80 induced significant levels of MDSC in vivo. CBD administration in mice induced G-CSF, CXCL1 and M-CSF, but not GM-CSF. G-CSF was found to play a key role in MDSC mobilization inasmuch as neutralizing G-CSF caused a significant decrease in MDSC. Lastly, CBD enhanced the transcriptional activity of PPARγ in luciferase reporter assay, and PPARγ selective antagonist completely inhibited MDSC induction in vivo suggesting its critical role. Together, the results suggest that CBD may induce activation of PPARγ in mast cells leading to secretion of G-CSF and consequent MDSC mobilization. CBD being a major component of Cannabis, our study indicates that marijuana may modulate or dysregulate the immune system by mobilizing MDSC. PMID:25917103

Id1, Id2 and Id3 are induced in rat melanotrophs of the pituitary gland by dopamine suppression under continuous stress.

PubMed

Konishi, H; Ogawa, T; Nakagomi, S; Inoue, K; Tohyama, M; Kiyama, H

2010-09-15

In rats under continuous stress (CS) there is decreased hypothalamic dopaminergic innervation to the intermediate lobe (IL) of the pituitary gland, which causes hyperactivation and subsequent degeneration of melanotrophs in the IL. In this study, we investigated the molecular basis for the changes that occur in melanotrophs during CS. Using microarray analysis, we identified several genes differentially expressed in the IL under CS conditions. Among the genes up-regulated under CS conditions, we focused on the inhibitor of DNA binding/differentiation (Id) family of dominant negative basic helix-loop-helix (bHLH) transcription factors. RT-PCR, Western blotting and in situ hybridization confirmed the significant inductions of Id1, Id2 and Id3 in the IL of CS rats. Administration of the dopamine D2 receptor agonist bromocriptine prevented the inductions of Id1-3 in the IL of CS rats, whereas application of the dopamine D2 antagonist sulpiride induced significant expressions of Id1-3 in the IL of normal rats. Moreover, an in vitro study using primary cultured melanotrophs demonstrated a direct effect on Id1-3 inductions by dopamine suppression. These results suggest that the decreased dopamine levels in the IL during CS induce Id1-3 expressions in melanotrophs. Because Id family members inhibit various bHLH transcription factors, it is conceivable that the induced Id1-3 would cooperatively modulate gene expressions in melanotrophs under CS conditions to induce hormone secretion. (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Diagnosis of the three-phase induction motor using thermal imaging

NASA Astrophysics Data System (ADS)

Glowacz, Adam; Glowacz, Zygfryd

2017-03-01

Three-phase induction motors are used in the industry commonly for example woodworking machines, blowers, pumps, conveyors, elevators, compressors, mining industry, automotive industry, chemical industry and railway applications. Diagnosis of faults is essential for proper maintenance. Faults may damage a motor and damaged motors generate economic losses caused by breakdowns in production lines. In this paper the authors develop fault diagnostic techniques of the three-phase induction motor. The described techniques are based on the analysis of thermal images of three-phase induction motor. The authors analyse thermal images of 3 states of the three-phase induction motor: healthy three-phase induction motor, three-phase induction motor with 2 broken bars, three-phase induction motor with faulty ring of squirrel-cage. In this paper the authors develop an original method of the feature extraction of thermal images MoASoID (Method of Areas Selection of Image Differences). This method compares many training sets together and it selects the areas with the biggest changes for the recognition process. Feature vectors are obtained with the use of mentioned MoASoID and image histogram. Next 3 methods of classification are used: NN (the Nearest Neighbour classifier), K-means, BNN (the back-propagation neural network). The described fault diagnostic techniques are useful for protection of three-phase induction motor and other types of rotating electrical motors such as: DC motors, generators, synchronous motors.

Induction Specificity and Catabolite Repression of the Early Enzymes in Camphor Degradation by Pseudomonas putida

PubMed Central

Hartline, Richard A.; Gunsalus, I. C.

1971-01-01

The ability of bornane and substituted bornanes to induce the early enzymes for d(+)-camphor degradation and control of these enzymes by catabolite repression were studied in a strain of a Pseudomonas putida. Bornane and 20 substituted bornane compounds showed induction. Of these 21 compounds, bornane and 8 of the substituted bornanes provided induction without supporting growth. Oxygen, but not nitrogen, enhanced the inductive potency of the unsubstituted bornane ring. All bornanedione isomers caused induction, and those with substituents on each of the three consecutive carbon atoms, including the methyl group at the bridgehead carbon, showed induction without supporting growth. Although it was not possible to obtain experimental data for a case of absolute gratuitous induction by compounds not supporting growth, indirect evidence in support of gratuitous induction is presented. It is proposed that the ability of P. putida to tolerate the unusually high degree of possible gratuitous induction observed for camphor catabolism may be related to the infrequent occurrence of bicyclic ring structures in nature. Survival of an organism with a broad specificity for gratuitous induction is discussed. Glucose and succinate, but not glutamate, produced catabolite repression of the early camphor-degrading enzymes. Pathway enzymes differ in their degree of sensitivity to succinate-provoked catabolite repression. The ability of a compound to produce catabolite repression is not, however, directly related to the duration of the lag period (diauxic lag) between growth on camphor and growth on the repressing compound. PMID:5573731

Differences in sensitivity of murine spermatogonia and somatic cells in vivo to sister-chromatid exchange induction by nitrosoureas.

PubMed

Morales-Ramírez, P; Cruz-Vallejo, V; Rodríguez-Reyes, R

2001-07-01

Previously published data indicate that spermatogonia (SPG) are less sensitive to a sister-chromatid exchange (SCE) induction for different mutagens. In an earlier study, we have observed that bromodeoxyuridine (BrdU) substituted murine SPG are less sensitive to SCE induction by gamma ray in cells, than bone marrow (BM) and salivary gland (SG) cells in vivo. This was interpreted to mean that SPG are more efficient in DNA repair or are less prone to SCE induction. That the lower induction of SCE could be due to a reduced accessibility of mutagens to the SPG by virtue of a physiological barrier, was discarded by using gamma radiation. The aim of the present study was to establish whether or not there are differences in SCE induction by nitrosoureas among SPG, SG and BM cells with BrdU substituted or unsubstituted DNA. It was observed that SCE induction by methylnitrosourea (MNU) or by ethylnitrosourea (ENU) in SPG was, respectively, five and two times lower than in SG, and ten and three times lower than in BM. In SPG after BrdU incorporation, there was no increase in efficiency of SCE induction; in fact, there was even a slight decrease by exposure to MNU or ENU. BM and SG cells showed an increased efficiency in SCE induction after BrdU incorporation. This implies that SPG are also less sensitive to SCE induction by nitrosoureas, which cause a different kind of damage from previously assayed mutagens.

Roles of MAPK pathway activation during cytokine induction in BEAS-2B cells exposed to fine World Trade Center (WTC) dust.

PubMed

Wang, Shang; Prophete, Colette; Soukup, Joleen M; Chen, Lung-Chi; Costa, Max; Ghio, Andrew; Qu, Qingshan; Cohen, Mitchell D; Chen, Haobin

2010-01-01

The World Trade Center (WTC) collapse on September 11, 2001 released copious amounts of particulate matter (PM) into the atmosphere of New York City. Follow-up studies on persons exposed to the dusts have revealed a severely increased rate for asthma and other respiratory illnesses. There have only been a few studies that have sought to discern the possible mechanisms underlying these untoward pathologies. In one study, an increased cytokine release was detected in cells exposed to WTC fine dusts (PM₂.₅ fraction or WTC₂.₅). However, the mechanism(s) for these increases has yet to be fully defined. Because activation of the mitogen-activated protein kinase (MAPK) signaling pathways is known to cause cytokine induction, the current study was undertaken to analyze the possible involvement of these pathways in any increased cytokine formation by lung epithelial cells (as BEAS-2B cells) exposed to WTC₂.₅. Our results showed that exposure to WTC₂.₅ for 5 hr increased interleukin-6 (IL-6) mRNA expression in BEAS-2B cells, as well as its protein levels in the culture media, in a dose-dependent manner. Besides IL-6, cytokine multiplex analyses revealed that formation of IL-8 and -10 was also elevated by the exposure. Both extracellular signal-regulated kinase (ERK) and p38, but not c-Jun N-terminal protein kinase, signaling pathways were found to be activated in cells exposed to WTC₂.₅. Inactivation of ERK signaling pathways by PD98059 effectively blocked IL-6, -8, and -10 induction by WTC₂.₅; the p38 kinase inhibitor SB203580 significantly decreased induction of IL-8 and -10. Together, our data demonstrated activation of MAPK signaling pathway(s) likely played an important role in the WTC₂.₅-induced formation of several inflammatory (and, subsequently, anti-inflammatory) cytokines. The results are important in that they help to define one mechanism via which the WTC dusts may have acted to cause the documented increases in asthma and other inflammation-associated respiratory dysfunctions in the individuals exposed to the dusts released from the WTC collapse.

Effect of hydrocortisone on cell morphology in C6 cells: the role of microfilaments in the inductive process. [Cytochalasin B; glycerol phosphate dehydrogenase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berliner, J.A.; Bennett, K.; de Vellis, J.

Hydrocortisone induced cell spreading and the formation of microfilaments in C6 cells with a time course similar to that found for the induction of GPDH. Cytochalasin B caused a rapid and reversible cell rounding and microfilament breakdown. Breakdown of both sheath and network microfilaments occurred within 1 hour; after removal of cytochalasin B, reversal of morphological effects began within 30 min. High calcium was found to block reversal of the cytochalasin B induced alteration, but did not affect shape or microfilaments in non-cytochalasin B treated cells. It is concluded that since microfilament induction occurs late and the block in synthesismore » of GPDH by cytochalasin B occurs within hours after addition, microfilaments induced by hydrocortisone are probably not important in the sequence of events leading to GPDH induction. But, however, microfilaments present in uninduced cells may be important in the sequence of GPDH induction, since treatment with cytochalasin B rapidly breaks these down and also inhibits GPDH induction by hydrocortisone.« less

High density growth of T7 expression strains with auto-induction option

DOEpatents

Studier, F William [Stony Brook, NY

2009-07-14

Disclosed is a method for promoting auto-induction of transcription of cloned DNA in cultures of bacterial cells grown batchwise, the transcription being under the control of a promoter whose activity can be induced by an exogenous inducer whose ability to induce said promoter is dependent on the metabolic state of said bacterial cells. Initially, a culture media is provided which includes: i) an inducer that causes induction of transcription from said promoter in said bacterial cells; and ii) a metabolite that prevents induction by said inducer, the concentration of said metabolite being adjusted so as to substantially preclude induction by said inducer in the early stages of growth of the bacterial culture, but such that said metabolite is depleted to a level that allows induction by said inducer at a later stage of growth. The culture medium is inoculated with a bacterial inoculum, the inoculum comprising bacterial cells containing cloned DNA, the transcription of which is induced by said inducer. The culture is then incubated under conditions appropriate for growth of the bacterial cells.

Zebrafish fgf3 and fgf8 encode redundant functions required for otic placode induction.

PubMed

Phillips, B T; Bolding, K; Riley, B B

2001-07-15

Members of the fibroblast growth factor (FGF) family of peptide ligands have been implicated in otic placode induction in several vertebrate species. Here, we have functionally analyzed the roles of fgf3 and fgf8 in zebrafish otic development. The role of fgf8 was assessed by analyzing acerebellar (ace) mutants. fgf3 function was disrupted by injecting embryos with antisense morpholino oligomers (MO) specifically designed to block translation of fgf3 transcripts. Disruption of either fgf3 or fgf8 causes moderate reduction in the size of the otic vesicle. Injection of fgf3-MO into ace/ace mutants causes much more severe reduction or complete loss of otic tissue. Moreover, preplacode cells fail to express pax8 and pax2.1, indicating disruption of early stages of otic induction in fgf3-depleted ace/ace mutants. Both fgf3 and fgf8 are normally expressed in the germring by 50% epiboly and are induced in the primordium of rhombomere 4 by 80% epibloy. In addition, fgf3 is expressed during the latter half of gastrulation in the prechordal plate and paraxial cephalic mesendoderm, tissues that either pass beneath or persist near the prospective otic ectoderm. Conditions that alter the pattern of expression of fgf3 and/or fgf8 cause corresponding changes in otic induction. Loss of maternal and zygotic one-eyed pinhead (oep) does not alter expression of fgf3 or fgf8 in the hindbrain, but ablates mesendodermal sources of fgf signaling and delays otic induction by several hours. Conversely, treatment of wild-type embryos with retinoic acid greatly expands the periotic domains of expression of fgf3, fgf8, and pax8 and leads to formation of supernumerary and ectopic otic vesicles. These data support the hypothesis that fgf3 and fgf8 cooperate during the latter half of gastrulation to induce differentiation of otic placodes. Copyright 2001 Academic Press.

Structure induction in diagnostic causal reasoning.

PubMed

Meder, Björn; Mayrhofer, Ralf; Waldmann, Michael R

2014-07-01

Our research examines the normative and descriptive adequacy of alternative computational models of diagnostic reasoning from single effects to single causes. Many theories of diagnostic reasoning are based on the normative assumption that inferences from an effect to its cause should reflect solely the empirically observed conditional probability of cause given effect. We argue against this assumption, as it neglects alternative causal structures that may have generated the sample data. Our structure induction model of diagnostic reasoning takes into account the uncertainty regarding the underlying causal structure. A key prediction of the model is that diagnostic judgments should not only reflect the empirical probability of cause given effect but should also depend on the reasoner's beliefs about the existence and strength of the link between cause and effect. We confirmed this prediction in 2 studies and showed that our theory better accounts for human judgments than alternative theories of diagnostic reasoning. Overall, our findings support the view that in diagnostic reasoning people go "beyond the information given" and use the available data to make inferences on the (unobserved) causal rather than on the (observed) data level. (c) 2014 APA, all rights reserved.

Patulin causes DNA damage leading to cell cycle arrest and apoptosis through modulation of Bax, p{sup 53} and p{sup 21/WAF1} proteins in skin of mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saxena, Neha; Ansari, Kausar M.; Kumar, Rahul

2009-01-15

Patulin (PAT), a mycotoxin found in apples, grapes, oranges, pear and peaches, is a potent genotoxic compound. WHO has highlighted the need for the study of cutaneous toxicity of PAT as manual labour is employed during pre and post harvest stages, thereby causing direct exposure to skin. In the present study cutaneous toxicity of PAT was evaluated following topical application to Swiss Albino mice. Dermal exposure of PAT, to mice for 4 h resulted in a dose (40-160 {mu}g/animal) and time (up to 6 h) dependent enhancement of ornithine decarboxylase (ODC), a marker enzyme of cell proliferation. The ODC activitymore » was found to be normal after 12 and 24 h treatment of patulin. Topical application of PAT (160 {mu}g/100 {mu}l acetone) for 24-72 h caused (a) DNA damage in skin cells showing significant increase (34-63%) in olive tail moment, a parameter of Comet assay (b) significant G 1 and S-phase arrest along with induction of apoptosis (2.8-10 folds) as shown by annexin V and PI staining assay through flow cytometer. Moreover PAT leads to over expression of p{sup 21/WAF1} (3.6-3.9 fold), pro apoptotic protein Bax (1.3-2.6) and tumor suppressor wild type p{sup 53} (2.8-3.9 fold) protein. It was also shown that PAT induced apoptosis was mediated through mitochondrial intrinsic pathway as revealed through the release of cytochrome C protein in cytosol leading to enhancement of caspase-3 activity in skin cells of mice. These results suggest that PAT has a potential to induce DNA damage leading to p{sup 53} mediated cell cycle arrest along with intrinsic pathway mediated apoptosis that may also be correlated with enhanced polyamine production as evident by induction of ODC activity, which may have dermal toxicological implications.« less

INDUCTION AND SUPPRESSION OF CYTOCHROME P450 1A BY 3,3', 4,4', 5-PENTACHLOROBIPHENYL AND ITS RELATIONSHIP TO OXIDATIVE STRESS IN THE MARINE FISH SCUP (STENOTOMUS CHRYSOPS). (R827102)

EPA Science Inventory

Abstract

The planar polychlorinated biphenyl (PCB) 3,3',4,4'-tetrachlorobiphenyl (TCB) causes dose-dependent induction and post-transcriptional suppression of hepatic cytochrome P450 1A (CYP1A) in the marine teleost scup (Stenotomus chrysops). That suppr...

Involvement of ROS-p38-H2AX axis in novel curcumin analogues-induced apoptosis in breast cancer cells.

PubMed

Dong, Yinhui; Yin, Shutao; Song, Xinhua; Huo, Yazhen; Fan, Lihong; Ye, Min; Hu, Hongbo

2016-04-01

Curcumin-based structural modification for developing more effective curcumin analogues has been drawning increasing attention. As alternative approach, using LC/MS guided purification, we previously obtained a series of novel natural terpene-conjugated curcuminoids from turmeric, and some of them exhibited even more potent anti-cancer activity against multiple types of cancer cells than curcumin. The purpose of this follow-up study was designed to decipher the mechanisms involved in anti-cancer activity of these novel curcumin analogues. Apoptosis was evaluated using sub-G1 analysis by flow cytometry and Cell Death ELISA Kit. Changes of protein expression were analyzed by western blotting. RNA interference was employed to inhibit expression of specific protein. We found that bisabolocurcumin ether (T1) and demethoxybisabolocurcumin ether (T2) were able to trigger much stronger apoptosis induction in multiple types of cancer cells than curcumin, which was attributed to persistent and stronger ROS generation. ROS induction by T1 resulted in activation of p38/H2AX axis and p53. Inhibition of p38/H2AX led to a significant reduction of apoptosis, whereas inactivation of p53 caused a dramatically enhanced H2AX phosphorylation and apoptosis induction, suggesting activation of p38/H2AX contributed to apoptosis induction by T1, whereas p53 activation protected novel curcumins-induced apoptosis via suppression of H2AX activation. Our findings provide mechanistic support for the potential use of terpene-conjugated curcuminoids as a novel class of cancer chemopreventive agents. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Increased Dietary Sodium Induces COX2 Expression by activating NFκB in Renal Medullary Interstitial Cells

PubMed Central

Zhao, Min; Davis, Linda S.; Blackwell, Timothy S.; Yull, Fiona; Breyer, Matthew D.; Hao, Chuan-Ming

2013-01-01

High salt diet induces renal medullary COX2 expression. Selective blockade of renal medullary COX2 activity in rats causes salt sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NFκB in mediating this COX2 induction in response to increased dietary salt. High salt diet (8% NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6J mice. Co-immunofluorescence using a COX2 antibody and antibodies against AQP2, ClC-K, AQP1 and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a 7 fold increase of luciferase activity in the renal medulla of the NFκB-luciferase reporter mice following high salt diet, and a robust induction of EGFP expression mainly in renal medullary interstitial cells of the NFκB-EGFP reporter mice following high salt diet. Treating high salt diet fed C57Bl/6J mice with selective IκB kinase inhibitor IMD-0354 (8mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary PGE2. These data therefore suggest that renal medullary interstitial cell NFκB plays an important role in mediating renal medullary COX2 expression and promoting renal PGE2 synthesis in response to increased dietary sodium. PMID:23900806

Effective Induction Heating around Strongly Magnetized Stars

NASA Astrophysics Data System (ADS)

Kislyakova, K. G.; Fossati, L.; Johnstone, C. P.; Noack, L.; Lüftinger, T.; Zaitsev, V. V.; Lammer, H.

2018-05-01

Planets that are embedded in the changing magnetic fields of their host stars can experience significant induction heating in their interiors caused by the planet’s orbital motion. For induction heating to be substantial, the planetary orbit has to be inclined with respect to the stellar rotation and dipole axes. Using WX UMa, for which the rotation and magnetic axes are aligned, as an example, we show that for close-in planets on inclined orbits, induction heating can be stronger than the tidal heating occurring inside Jupiter’s satellite Io; namely, it can generate a surface heat flux exceeding 2 W m‑2. An internal heating source of such magnitude can lead to extreme volcanic activity on the planet’s surface, possibly also to internal local magma oceans, and to the formation of a plasma torus around the star aligned with the planetary orbit. A strongly volcanically active planet would eject into space mostly SO2, which would then dissociate into oxygen and sulphur atoms. Young planets would also eject CO2. Oxygen would therefore be the major component of the torus. If the O I column density of the torus exceeds ≈1012 cm‑2, the torus could be revealed by detecting absorption signatures at the position of the strong far-ultraviolet O I triplet at about 1304 Å. We estimate that this condition is satisfied if the O I atoms in the torus escape the system at a velocity smaller than 1–10 km s‑1. These estimates are valid also for a tidally heated planet.

Induction of p53-mediated apoptosis in splenocytes and thymocytes of C57BL/6 mice exposed to perfluorooctane sulfonate (PFOS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Guang-Hui, E-mail: ghdong@mail.cmu.edu.cn; Wang, Jing; Zhang, Ying-Hua

2012-10-15

Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in human and wildlife tissues. It has been reported that PFOS can cause atrophy of the immune organs and apoptosis of immunocytes in rodents. However, the mechanism behind such cause is still unclear. To understand the model of cell death and its mechanism on lymphoid cells in vivo, we conducted a dose/response experiment in which 4 groups of male adult C57BL/6 mice (12 mice per group) were dosed daily by oral gavage with PFOS at 0, 0.0167, 0.0833, or 0.8333 mg/kg/day, yielding targeted Total Administered Dose (TAD) of 0, 1, 5,more » or 50 mg PFOS/kg, respectively, over 60 days. The results showed that spleen and thymus weight were significantly reduced in the highest PFOS-dose-group (TAD 50 mg PFOS/kg) compared to the control group, whereas liver weight was significantly increased. We analyzed the cell death via apoptosis with an annexin-V/propidium iodide assay by flow cytometry, and observed that both the percentage of apoptosis and the expression of the pro-apoptotic proteins p53 in splenocytes and thymocytes increased in a dose-related manner after PFOS treatment. We also observed that PFOS induced p53-dependent apoptosis through the cooperation between the Bcl-xl down regulation without changing the Bcl-2 and Bax expression. The down regulation of Bcl-xl was strongly indicating mitochondrial involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in PFOS induced toxic environment in the host. -- Highlights: ► PFOS immunotoxicity is caused by induction of apoptosis via the p53 activation. ► PFOS exposure can induce down regulation of Bcl-xl. ► Mitochondria are involved in PFOS-induced apoptosis. ► PFOS exposure can cause the release of cytochrome c and activation of caspase-3.« less

The clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation.

PubMed

Mizota, Toshiyuki; Matsukawa, Shino; Fukagawa, Hiroshi; Daijo, Hiroki; Tanaka, Tomoharu; Chen, Fengshi; Date, Hiroshi; Fukuda, Kazuhiko

2015-08-01

We examined the clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation (post-HSCT), focusing on ventilatory management. We aimed to determine the incidence of oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction in post-HSCT lung transplant recipients, and to explore factors associated with their development. Nineteen consecutive patients who underwent lung transplantation post-HSCT at Kyoto University Hospital (Japan) were retrospectively studied. Data regarding patient characteristics, preoperative examination, and clinical course during anesthetic induction were analyzed. The incidence of oxygen desaturation (SpO2 < 90 %) during anesthetic induction and severe respiratory acidosis (pH < 7.2) after anesthetic induction were 21.1 and 26.3 %, respectively. Reduced dynamic compliance (Cdyn) during mechanical ventilation was significantly associated with oxygen desaturation during anesthetic induction (p = 0.01), as well as severe respiratory acidosis after anesthetic induction (p = 0.01). The preoperative partial pressure of carbon dioxide in arterial blood (PaCO2; r = -0.743, p = 0.002) and body mass index (BMI; r = 0.61, p = 0.021) significantly correlated with Cdyn, and multivariate analysis revealed that both PaCO2 and BMI were independently associated with Cdyn. Oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction frequently occur in post-HSCT lung transplant recipients. Low Cdyn may, at least partially, explain oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction. Moreover, preoperative hypercapnia and low BMI were predictive of low Cdyn.

Health Effects in Fish of Long-Term Exposure to Effluents from Wastewater Treatment Works

PubMed Central

Liney, Katherine E.; Hagger, Josephine A.; Tyler, Charles R.; Depledge, Michael H.; Galloway, Tamara S.; Jobling, Susan

2006-01-01

Concern has been raised in recent years that exposure to wastewater treatment effluents containing estrogenic chemicals can disrupt the endocrine functioning of riverine fish and cause permanent alterations in the structure and function of the reproductive system. Reproductive disorders may not necessarily arise as a result of estrogenic effects alone, and there is a need for a better understanding of the relative importance of endocrine disruption in relation to other forms of toxicity. Here, the integrated health effects of long-term effluent exposure are reported (reproductive, endocrine, immune, genotoxic, nephrotoxic). Early life-stage roach, Rutilus rutilus, were exposed for 300 days to treated wastewater effluent at concentrations of 0, 15.2, 34.8, and 78.7% (with dechlorinated tap water as diluent). Concentrations of treated effluents that induced feminization of male roach, measured as vitellogenin induction and histological alteration to gonads, also caused statistically significant alterations in kidney development (tubule diameter), modulated immune function (differential cell count, total number of thrombocytes), and caused genotoxic damage (micronucleus induction and single-strand breaks in gill and blood cells). Genotoxic and immunotoxic effects occurred at concentrations of wastewater effluent lower than those required to induce recognizable changes in the structure and function of the reproductive endocrine system. These findings emphasize the need for multiple biological end points in tests that assess the potential health effects of wastewater effluents. They also suggest that for some effluents, genotoxic and immune end points may be more sensitive than estrogenic (endocrine-mediated) end points as indicators of exposure in fish. PMID:16818251

Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance

NASA Astrophysics Data System (ADS)

Hotamisligil, Gokhan S.; Shargill, Narinder S.; Spiegelman, Bruce M.

1993-01-01

Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-α protein was also elevated locally and systemically. Neutralization of TNF-α in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-α in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

Action of hydrogen peroxide on degradation of DNA after irradiation in Escherichia coli.

PubMed

Keller, K M; Pollard, E C

1977-05-01

Hydrogen peroxide (H2O2), which produces breaks in cellular DNA, has not hitherto been shown to cause degradation of DNA. In this investigation it is shown that if transcription is blocked with rifampin, treatment with H2O2 causes degradation of DNA to nearly the same extent as does gamma-radiation. Further, if cells are given a treatment with H2O2 and incubated for 50 min, the amount of degradation in a second treatment is markedly less. This is attributed to the induction of the inhibitor of post-irradiation degradation of DNA (prd) by the first treatment. There is thus a double action of H2O2: first, to induce inhibition, and second, to cause degradation of DNA to begin in non-induced cells. The genetic dependence of induction by H2O2 mimics that of ionizing radiation. Accordingly, the induction process does not occur in recA- and lex- cells, because they are not inducible and is absent in recB- cells because they lack exonuclease V, the major component of prd. Potassium iodide (KI), an OH radical scavenger, negates the action of peroxide on DNA. The results obtained in this study suggest a possible theory for the evolution of radiation response systems

Inactivation and mutation induction in Saccharomyces cerevisiae exposed to simulated sunlight: evaluation of action spectra.

PubMed

Schenk-Meuser, K; Pawlowsky, K; Kiefer, J

1992-07-15

The effectiveness of polychromatic light irradiation was investigated for haploid yeast cells. Inactivation and mutation induction were measured in both a RAD-wildtype strain and an excision-repair defective strain. The behaviour of vegetative "wet" cells was compared to that of dehydrated cells. The aim of the study was to assess the interaction of UVC with other wavelengths in cells of different states of humidity. The irradiation procedure was therefore carried out using a solar simulator either with full spectrum or with a UVC-blocking filter (modified sunlight) added. The results were analysed on the basis of separately determined action spectra. The summation of the efficiency of individual wavelengths was compared to the values obtained from polychromatic irradiation. It is shown that the effects caused by the whole-spectrum irradiation in wet cells can be predicted sufficiently from the calculation, while dried wildtype cells exhibit higher mutation rates. Thus it can be assumed that drying-specific damage leads to lethal and mutagenic lesions which are processed in different ways, causing a synergistic behaviour in mutation induction. Irradiation of vegetative cells with modified sunlight (UVC-) results in less inactivation and lower mutation rates than were calculated. From these results it can be concluded that this antagonistic behaviour is caused by the interaction of near-UV photoproducts.

FGF-mediated mesoderm induction involves the Src-family kinase Laloo.

PubMed

Weinstein, D C; Marden, J; Carnevali, F; Hemmati-Brivanlou, A

1998-08-27

During embryogenesis, inductive interactions underlie the development of much of the body plan. In Xenopus laevis, factors secreted from the vegetal pole induce mesoderm in the adjacent marginal zone; members of both the transforming growth factor-beta (TGF-beta) and fibroblast growth factor (FGF) ligand families seem to have critical roles in this process. Here we report the identification and characterization of laloo, a novel participant in the signal transduction cascade linking extracellular, mesoderm-inducing signals to the nucleus, where alteration of cell fate is driven by changes in gene expression. Overexpression of laloo, a member of the Src-related gene family, in Xenopus embryos gives rise to ectopic posterior structures that frequently contain axial tissue. Laloo induces mesoderm in Xenopus ectodermal explants; this induction is blocked by reagents that disrupt the FGF signalling pathway. Conversely, expression of a dominant-inhibitory Laloo mutant blocks mesoderm induction by FGF and causes severe posterior truncations in vivo. This work provides the first evidence that a Src-related kinase is involved in vertebrate mesoderm induction.

Uncertain decision tree inductive inference

NASA Astrophysics Data System (ADS)

Zarban, L.; Jafari, S.; Fakhrahmad, S. M.

2011-10-01

Induction is the process of reasoning in which general rules are formulated based on limited observations of recurring phenomenal patterns. Decision tree learning is one of the most widely used and practical inductive methods, which represents the results in a tree scheme. Various decision tree algorithms have already been proposed such as CLS, ID3, Assistant C4.5, REPTree and Random Tree. These algorithms suffer from some major shortcomings. In this article, after discussing the main limitations of the existing methods, we introduce a new decision tree induction algorithm, which overcomes all the problems existing in its counterparts. The new method uses bit strings and maintains important information on them. This use of bit strings and logical operation on them causes high speed during the induction process. Therefore, it has several important features: it deals with inconsistencies in data, avoids overfitting and handles uncertainty. We also illustrate more advantages and the new features of the proposed method. The experimental results show the effectiveness of the method in comparison with other methods existing in the literature.

Efficiency of the Lung Flute for sputum induction in patients with presumed pulmonary tuberculosis.

PubMed

Sakashita, Kentaro; Fujita, Akira; Takamori, Mikio; Nagai, Takayuki; Matsumoto, Tomoshige; Saito, Takefumi; Nakagawa, Taku; Ogawa, Kenji; Shigeto, Eriko; Nakatsumi, Yasuto; Goto, Hajime; Mitarai, Satoshi

2018-04-01

High quality sputum helps increase the sensitivity of the diagnosis of pulmonary tuberculosis. To evaluate the efficiency of the acoustic device (Lung Flute; LF) in sputum induction compared with the conventional method, hypertonic saline inhalation (HSI). In this crossover study, patients with presumed pulmonary tuberculosis submitted 3 consecutive sputa: the first sputum without induction and the second and third ones using LF and HSI. We compared the efficiency of the 2 induction methods. Sixty-four participants were eligible. Thirty-five (54.6%) patients had negative smears on the first sputum without induction. Among those patients, 25.7% and 22.9% patients were smear-positive after using LF and HSI, respectively (P = .001). The positive conversion rate was not significantly different between the methods. The first samples without induction yielded 65.7% positive cultures, whereas 71.4% and 77.1% of the samples from LF and HSI were positive, respectively (P = .284). Similar results were observed in the nucleic acid amplification test [no induction (60.0%), LF (72.0%) and HSI (60.0%); P = .341]. In 29 smear-positive patients on the first sputum without induction, we observed no significant increase in smear grade, culture yield and nucleic acid amplification test positivity with either method. LF tended to induce fewer adverse events; desaturation (3.1% vs 11.1%; P = .082) and throat pain (1.5% vs 9.5%; P = .057). LF showed significantly fewer total adverse events (15.8% vs 34.9%; P = .023). Our study showed LF had similar sputum induction efficiency to HSI with relatively fewer complications. © 2017 The Authors. The Clinical Respiratory Journal Published by John Wiley & Sons Ltd.

Anesthesia with isoflurane and sevoflurane in the crested serpent eagle (Spilornis cheela hoya): minimum anesthetic concentration, physiological effects, hematocrit, plasma chemistry and behavioral effects.

PubMed

Chan, Fang-Tse; Chang, Geng-Ruei; Wang, Hsien-Chi; Hsu, Tien-Huan

2013-12-30

The initial goal of this study was to determine the minimum anesthetic concentration (MAC) for isoflurane (ISO) and sevoflurane (SEVO) for the crested serpent eagle. Next, we compared the anesthetic effects of each on the physiological effects, hematocrit, plasma chemistry values and behavior in spontaneously breathing captive adult crested serpent eagles. Sixteen eagles were randomly allocated to two groups for anesthesia with ISO (n=8) or SEVO (n=8). First, we measured the MAC values of ISO and SEVO, and four weeks later, we investigated the effect of each on the physiological effects, hematocrit (HCT) and plasma chemistry values. The MAC values of ISO and SEVO for crested serpent eagles were 1.46 ± 0.30 and 2.03 ± 0.32%, respectively. The results revealed no significant differences between the two anesthetics in induction time, while time of extubation to recovery was significantly shorter with SEVO. A time-related increase in end-tidal CO₂ and decreases in body temperature and respiratory rates were observed during anesthesia with each anesthetic. There were no significant differences between the effect of the two anesthetics on heart rate, hematocrit, plasma chemistry values or respiration, although each caused minor respiration depression. We concluded that SEVO is a more effective inhalant agent than ISO for use in eagles, showing the most rapidest induction and recovery from anesthesia.

Use of high-dose nandrolone aggravates septic shock in a mouse model.

PubMed

Lin, Che; Chen, Shou-Tung; Chien, Su-Yu; Kuo, Shou-Jen; Chen, Dar-Ren

2011-06-01

Nandrolone, an anabolic-androgenic steroid, is widely misused by athletes who wish to rapidly increase muscle mass and performance. An increasing number of reports have indicated that nandrolone may affect and modulate the immune system. This study aimed to investigate the effects of nandrolone on septic shock-caused immune responses and the cellular mechanism of action using a sepsis murine model. Before septic shock induction, BALB/c mice were given a high dose of nandrolone or peanut oil only. After septic shock induction, mice were sacrificed at different time points. Their blood and tissue specimens were analyzed. It was found that the high-dose nandrolone group had significantly increased mortality compared with the control group (p<0.001). The serum malondialdehyde level was significantly increased in the high-dose group compared with the control group. Animals administered a high dose of nandrolone had significantly increased hepatic tumor necrosis factor-α or splenic interferon-γ at 0 and 6 hours. In lung tissue, insulin-like growth factor-1, insulin-like growth factor binding proteins (IGFBPs) and insulin-like growth factor-1 receptor, and IGFBP1 and IGFBP2 mRNA expression were increased in the high-dose nandrolone group at 6 hours. Nandrolone abuse may hasten the death of patients with septic shock and may aggravate septic shock in mice. Copyright © 2011. Published by Elsevier B.V.

Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1

DOE PAGES

Suresh Kumar, M. A.; Peluso, Michael; Chaudhary, Pankaj; ...

2015-07-24

Ionizing radiation causes degeneration of myelin, the insulating sheaths of neuronal axons, leading to neurological impairment. As radiation research on the central nervous system has predominantly focused on neurons, with few studies addressing the role of glial cells, we have focused our present research on identifying the latent effects of single/ fractionated -low dose of low/ high energy radiation on the role of base excision repair protein Apurinic Endonuclease-1, in the rat spinal cords oligodendrocyte progenitor cells ’ differentiation. Apurinic endonuclease-1 is predominantly upregulated in response to oxidative stress by low- energy radiation, and previous studies show significant induction ofmore » Apurinic Endonucle- ase-1 in neurons and astrocytes. Our studies show for the first time, that fractionation of pro- tons cause latent damage to spinal cord architecture while fractionation of HZE ( 28Si) induce increase in APE1 with single dose, which then decreased with fractionation. In conclusion, the oligoden- drocyte progenitor cells differentiation was skewed with increase in immature oligodendro- cytes and astrocytes, which likely cause the observed decrease in white matter, increased neuro-inflammation, together leading to the observed significant cognitive defects« less

Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suresh Kumar, M. A.; Peluso, Michael; Chaudhary, Pankaj

Ionizing radiation causes degeneration of myelin, the insulating sheaths of neuronal axons, leading to neurological impairment. As radiation research on the central nervous system has predominantly focused on neurons, with few studies addressing the role of glial cells, we have focused our present research on identifying the latent effects of single/ fractionated -low dose of low/ high energy radiation on the role of base excision repair protein Apurinic Endonuclease-1, in the rat spinal cords oligodendrocyte progenitor cells ’ differentiation. Apurinic endonuclease-1 is predominantly upregulated in response to oxidative stress by low- energy radiation, and previous studies show significant induction ofmore » Apurinic Endonucle- ase-1 in neurons and astrocytes. Our studies show for the first time, that fractionation of pro- tons cause latent damage to spinal cord architecture while fractionation of HZE ( 28Si) induce increase in APE1 with single dose, which then decreased with fractionation. In conclusion, the oligoden- drocyte progenitor cells differentiation was skewed with increase in immature oligodendro- cytes and astrocytes, which likely cause the observed decrease in white matter, increased neuro-inflammation, together leading to the observed significant cognitive defects« less

In vitro T lymphocyte adherence capabilities under the influence of lower induction values (0.1 - 0.01 mT) of 50 Hz external magnetic fields

NASA Astrophysics Data System (ADS)

Čoček, A.; Jandová, A.; Hahn, A.; Mártonová, J.; Ambruš, M.; Dohnalová, A.; Nedbalová, M.; Pokorný, J.

2011-12-01

Our research thus far has concerned the impact of external magnetic fields (50 Hz) and low (0.01-10 mT) induction on adherence capabilities of T lymphocytes obtained from the blood of patients with head and neck tumors. We know that the in vitro adherence capability of T lymphocytes towards surfaces in cancer patients is less than that of control. Previously, we have found that exposure to magnetic fields (50 Hz / 0.01-10 mT) increases the capability of T lymphocytes, in larynx/pharynx cancer patients, to adhere in vitro to surfaces, achieving almost physiological values, in not only pre-treatment patients but also those receiving treatment in the course of follow-up. The capability of T lymphocytes in controls (voluntary blood donors) to adhere to surfaces was also increased (50 Hz / 0.01-0.5 mT). The present study concentrates on the significance of the level of magnetic field induction in order to determine whether low induction values can restore T lymphocytes adherence capabilities. Testing a set of 20 patients showed a statistically significant difference (p < 0.05) in the in vitro adherence capacity of T lymphocytes between both 0.01 and 0.05, and 0.1 mT induction levels. In the control group (patients diagnosed with chronic sensorineural hearing loss) there was even a statistically significant difference between induction values of 0.05 and 0.01 mT. Therefore, we concluded that lower induction values resulted in a more biologically significant response.

Myocardial and Peripheral Ischemia Causes an Increase in Circulating Pregnancy-Associated Plasma Protein-A in Non-atherosclerotic, Non-heparinized Pigs.

PubMed

Steffensen, Lasse Bach; Poulsen, Christian Bo; Shim, Jeong; Bek, Marie; Jacobsen, Kevin; Conover, Cheryl A; Bentzon, Jacob Fog; Oxvig, Claus

2015-12-01

The usefulness of circulating pregnancy-associated plasma protein-A (PAPP-A) as a biomarker for acute coronary syndrome (ACS) is widely debated. We used the pig as a model to assess PAPP-A dynamics in the setting of myocardial ischemia. Induction of myocardial ischemia by ligation of the left anterior descending (LAD) coronary artery caused a systemic rise in PAPP-A. However, the ischemic myocardium was excluded as the source of PAPP-A. Interestingly, induction of ischemia in peripheral tissues by ligation of the left femoral artery caused a systemic rise in PAPP-A originating from the left hind limb. This is the first study to demonstrate PAPP-A elevations in the absence of atherosclerosis or heparin during myocardial ischemia. Our findings thus add to the current discussion of the usefulness of PAPP-A as a biomarker for ACS.

Inductive displacement sensors with a notch filter for an active magnetic bearing system.

PubMed

Chen, Seng-Chi; Le, Dinh-Kha; Nguyen, Van-Sum

2014-07-15

Active magnetic bearing (AMB) systems support rotating shafts without any physical contact, using electromagnetic forces. Each radial AMB uses two pairs of electromagnets at opposite sides of the rotor. This allows the rotor to float in the air gap, and the machine to operate without frictional losses. In active magnetic suspension, displacement sensors are necessary to detect the radial and axial movement of the suspended object. In a high-speed rotating machine equipped with an AMB, the rotor bending modes may be limited to the operating range. The natural frequencies of the rotor can cause instability. Thus, notch filters are a useful circuit for stabilizing the system. In addition, commercial displacement sensors are sometimes not suitable for AMB design, and cannot filter the noise caused by the natural frequencies of rotor. Hence, implementing displacement sensors based on the AMB structure is necessary to eliminate noises caused by natural frequency disturbances. The displacement sensor must be highly sensitive in the desired working range, and also exhibit a low interference noise, high stability, and low cost. In this study, we used the differential inductive sensor head and lock-in amplifier for synchronous demodulation. In addition, an active low-pass filter and a notch filter were used to eliminate disturbances, which caused by natural frequencies. As a consequence, the inductive displacement sensor achieved satisfactory linearity, high sensitivity, and disturbance elimination. This sensor can be easily produced for AMB applications. A prototype of these displacement sensors was built and tested.

Identification and characterization of Escherichia coli RS218-derived islands in the pathogenesis of E. coli meningitis.

PubMed

Xie, Yi; Kolisnychenko, Vitaliy; Paul-Satyaseela, Maneesh; Elliott, Simon; Parthasarathy, Geetha; Yao, Yufeng; Plunkett, Guy; Blattner, Frederick R; Kim, Kwang Sik

2006-08-01

Escherichia coli K1 is the most common gram-negative bacterium causing neonatal meningitis, but the mechanisms by which E. coli K1 causes meningitis are not clear. We identified 22 E. coli RS218-derived genomic islands (RDIs), using a comparative genome analysis of meningitis-causing E. coli K1 strain RS218 (O18:K1:H7) and laboratory K-12 strain MG1655. Series of RDI deletion mutants were constructed and examined for phenotypes relevant to E. coli K1 meningitis. We identified 9 RDI deletion mutants (RDI 1, 4, 7, 12, 13, 16, 20, 21, and 22) that exhibited defects in meningitis development. RDI 16 and 21 mutants had profound defects in the induction of a high level of bacteremia in neonatal rats, and RDI 4 mutants exhibited a moderate defect in the induction of bacteremia. RDI 1 and 22 mutants showed defects in the ability to invade human brain microvascular endothelial cells (HBMECs), and RDI 12 mutants were defective in the ability to bind to HBMECs. RDI 13 and 20 mutants were defective in the ability to both bind to and invade HBMECs. RDI 7 mutants were defective in the induction of bacteremia and in the ability to both bind to and invade HBMECs. These results provide a framework for the future discovery and analysis of bacteremia and meningitis caused by E. coli K1 strain RS218.

[In vivo study of the pharmacokinetic interaction of afobazole and losartan (cytochrome CYP2C9 substrate)].

PubMed

Gribakina, O G; Kolyvanov, G B; Litvin, A A; Zherdev, V P; Seredin, S B

2013-01-01

The influence of afobazole on isoenzyme CYP2C9 production in rats was studied using losartan as the marker drug. Single dose of losartan was administered orally without afobazole in a dose of 30 mg/kg and in the same single (30 mg/kg) on the background of 3- and 4-day administration of afobazole in a dose of 5, 25, 75, 100, and 125 mg/kg. At 5 mg/kg (effective dose for anxiolytic effect), afobazole did not cause any induction/inhibition effect on CYP2C9 isoenzyme. A multiple increase in afobazole dose was manifested by a moderate induction effect. The maximum induction effect of afobazole was achieved in a dose of 75 mg/kg. At doses above 75 mg/kg, the induction effect of afobazole was less pronounced.

Magma oceans and enhanced volcanism on TRAPPIST-1 planets due to induction heating

NASA Astrophysics Data System (ADS)

Kislyakova, K. G.; Noack, L.; Johnstone, C. P.; Zaitsev, V. V.; Fossati, L.; Lammer, H.; Khodachenko, M. L.; Odert, P.; Guedel, M.

2017-10-01

Low-mass M stars are plentiful in the Universe and often host small, rocky planets detectable with the current instrumentation. Recently, seven small planets have been discovered orbiting the ultracool dwarf TRAPPIST-1 te{Gillon16,Gillon17}. We examine the role of electromagnetic induction heating of these planets, caused by the star's rotation and the planet's orbital motion. If the stellar rotation and magnetic dipole axes are inclined with respect to each other, induction heating can melt the upper mantle and enormously increase volcanic activity, sometimes producing a magma ocean below the planetary surface. We show that induction heating leads the three innermost planets, one of which is in the habitable zone, to either evolve towards a molten mantle planet, or to experience increased outgassing and volcanic activity, while the four outermost planets remain mostly unaffected.

Cinnamaldehyde inhibits enzymatic browning of cut lettuce by repressing the induction of phenylalanine ammonia-lyase without promotion of microbial growth.

PubMed

Tanaka, Eriko; Okumura, Saya; Takamiya, Rikako; Hosaka, Hitomi; Shimamura, Yuko; Murata, Masatsune

2011-06-22

Cinnamaldehyde treatment inhibited the browning of cut lettuce during cold storage. In this study, to clarify the mechanism of inhibitory action of cinnamaldehyde against the browning and to show its microbiological merit, its effect on the browning of cut lettuce was compared to that of mild heat treatment. Both cinnamaldehyde and mild heat treatments inhibited the induction of phenylalanine ammonia-lyase (PAL) activity because of cutting. As a result, the biosynthesis of polyphenols, which are substrates of polyphenol oxidase, was inhibited. This reduction of polyphenol synthesis caused the inhibition of the browning. Cinnamaldehyde treatment repressed the induction of PAL mRNA, while mild heat treatment did not repress its induction. The increase in microbes in cut lettuce treated with cinnamaldehyde was less than that treated with mild heat after 12 days.

Protective Effect of Mangifera indica Linn., Cocos nucifera Linn., and Averrhoa carambola Linn. Extracts against Ultraviolet B-Induced Damage in Human Keratinocytes

PubMed Central

Ronpirin, Chalinee; Pattarachotanant, Nattaporn

2016-01-01

This study was aimed at investigating the antioxidant activity of Mangifera indica Linn., Cocos nucifera Linn., and Averrhoa carambola Linn. and their biological effect on human keratinocytes affected by the ultraviolet B (UVB), a major cause of cell damage and skin cancer through induction of DNA damage, production of reactive oxygen species (ROS), and apoptosis. The richest antioxidant activity was found in ethanol fraction of M. indica (21.32 ± 0.66 mg QE/g dry weight), while the lowest one was found in aqueous fractions of M. indica and C. nucifera (1.76 ± 2.10 and 1.65 ± 0.38 mg QE/g dry weight, respectively). Ethanol and aqueous fractions of A. carambola (250 µg/mL) significantly reduced the number of apoptotic cells. The expression of cleaved caspase 3 in UVB-treated group was significantly greater than that in untreated group. Both fractions of A. carambola (50, 100, and 250 µg/mL) significantly decreased the expression of cleaved caspase 3. Regarding the induction of DNA repair, ethanol (100 and 250 µg/mL) and aqueous (50, 100 and 250 µg/mL) fractions of A. carambola significantly decreased the percentage of cyclobutane pyrimidine dimers (CPD). Taken together, our results suggest that both fractions of A. carambola may be potentially developed for dermal applications. PMID:27057195

Chronic nitrate exposure alters reproductive physiology in fathead minnows.

PubMed

Kellock, Kristen A; Moore, Adrian P; Bringolf, Robert B

2018-01-01

Nitrate is a ubiquitous aquatic pollutant that is commonly associated with eutrophication and dead zones in estuaries around the world. At high concentrations nitrate is toxic to aquatic life but at environmental concentrations it has also been purported as an endocrine disruptor in fish. To investigate the potential for nitrate to cause endocrine disruption in fish, we conducted a lifecycle study with fathead minnows (Pimephales promelas) exposed to nitrate (0, 11.3, and 56.5 mg/L (total nitrate-nitrogen (NO 3 -N)) from <24 h post hatch to sexual maturity (209 days). Body mass, condition factor, gonadal somatic index (GSI), incidence of intersex, and vitellogenin induction were determined in mature male and female fish and plasma 11-keto testosterone (11-KT) was measured in males only. In nitrate-exposed males both 11-KT and vitellogenin were significantly induced when compared with controls. No significant differences occurred for body mass, condition factor, or GSI among males and intersex was not observed in any of the nitrate treatments. Nitrate-exposed females also had significant increases in vitellogenin compared to controls but no significant differences for mass, condition factor, or GSI were observed in nitrate exposed groups. Estradiol was used as a positive control for vitellogenin induction. Our findings suggest that environmentally relevant nitrate levels may disrupt steroid hormone synthesis and/or metabolism in male and female fish and may have implications for fish reproduction, watershed management, and regulation of nutrient pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Linking physiological and cellular responses to thermal stress: β-adrenergic blockade reduces the heat shock response in fish.

PubMed

Templeman, Nicole M; LeBlanc, Sacha; Perry, Steve F; Currie, Suzanne

2014-08-01

When faced with stress, animals use physiological and cellular strategies to preserve homeostasis. We were interested in how these high-level stress responses are integrated at the level of the whole animal. Here, we investigated the capacity of the physiological stress response, and specifically the β-adrenergic response, to affect the induction of the cellular heat shock proteins, HSPs, following a thermal stress in vivo. We predicted that blocking β-adrenergic stimulation during an acute heat stress in the whole animal would result in reduced levels of HSPs in red blood cells (RBCs) of rainbow trout compared to animals where adrenergic signaling remained intact. We first determined that a 1 h heat shock at 25 °C in trout acclimated to 13 °C resulted in RBC adrenergic stimulation as determined by a significant increase in cell swelling, a hallmark of the β-adrenergic response. A whole animal injection with the β2-adrenergic antagonist, ICI-118,551, successfully reduced this heat-induced RBC swelling. The acute heat shock caused a significant induction of HSP70 in RBCs of 13 °C-acclimated trout as well as a significant increase in plasma catecholamines. When heat-shocked fish were treated with ICI-118,551, we observed a significant attenuation of the HSP70 response. We conclude that circulating catecholamines influence the cellular heat shock response in rainbow trout RBCs, demonstrating physiological/hormonal control of the cellular stress response.

Differential suppression of glial nitric oxide synthase induction by structurally related tyrosine kinase inhibitors.

PubMed

Galea, E; Reddi, J; Feinstein, D L

1995-11-24

Incubation of C6 astrocytoma cells with bacterial endotoxin (lipopolysaccharide; LPS) plus interferon-gamma (IFN-gamma), or with a combination of cytokines (TNF-alpha, IL1-beta, and IFN-gamma) leads to high levels of inducible nitric oxide synthase (iNOS) expression. Previous results demonstrated a requirement for tyrosine kinase (TK) activities for iNOS induction. In the present study, a set of structurally related TK inhibitors, the tyrphostins (TYRs), were used to characterize possible differences between LPS and cytokine iNOS induction. All TYRs tested suppressed both types of induction. However, dose-response curves revealed significant differences in the IC50 values obtained for some TYRs (T25 and T56), and significant differences in the IC50 potency rank order when comparing inhibition of LPS versus cytokine-dependent iNOS induction. These results are consistent with differential TK utilization by the LPS versus cytokine pathways of iNOS induction, and establish a basis for developing further selective inhibitors of iNOS expression.

Induction of Mitochondrial Reactive Oxygen Species Production by Itraconazole, Terbinafine, and Amphotericin B as a Mode of Action against Aspergillus fumigatus

PubMed Central

Shekhova, Elena

2017-01-01

ABSTRACT Drug resistance in fungal pathogens is of incredible importance to global health, yet the mechanisms of drug action remain only loosely defined. Antifungal compounds have been shown to trigger the intracellular accumulation of reactive oxygen species (ROS) in human-pathogenic yeasts, but the source of those ROS remained unknown. In the present study, we examined the role of endogenous ROS for the antifungal activity of the three different antifungal substances itraconazole, terbinafine, and amphotericin B, which all target the fungal cell membrane. All three antifungals had an impact on fungal redox homeostasis by causing increased intracellular ROS production. Interestingly, the elevated ROS levels induced by antifungals were abolished by inhibition of the mitochondrial respiratory complex I with rotenone. Further, evaluation of lipid peroxidation using the thiobarbituric acid assay revealed that rotenone pretreatment decreased ROS-induced lipid peroxidation during incubation of Aspergillus fumigatus with itraconazole and terbinafine. By applying the mitochondrion-specific lipid peroxidation probe MitoPerOx, we also confirmed that ROS are induced in mitochondria and subsequently cause significant oxidation of mitochondrial membrane in the presence of terbinafine and amphotericin B. To summarize, our study suggests that the induction of ROS production contributes to the ability of antifungal compounds to inhibit fungal growth. Moreover, mitochondrial complex I is the main source of deleterious ROS production in A. fumigatus challenged with antifungal compounds. PMID:28848005

Toxicity of nano- and micro-sized ZnO particles in human lung epithelial cells

NASA Astrophysics Data System (ADS)

Lin, Weisheng; Xu, Yi; Huang, Chuan-Chin; Ma, Yinfa; Shannon, Katie B.; Chen, Da-Ren; Huang, Yue-Wern

2009-01-01

This is the first comprehensive study to evaluate the cytotoxicity, biochemical mechanisms of toxicity, and oxidative DNA damage caused by exposing human bronchoalveolar carcinoma-derived cells (A549) to 70 and 420 nm ZnO particles. Particles of either size significantly reduced cell viability in a dose- and time-dependent manner within a rather narrow dosage range. Particle mass-based dosimetry and particle-specific surface area-based dosimetry yielded two distinct patterns of cytotoxicity in both 70 and 420 nm ZnO particles. Elevated levels of reactive oxygen species (ROS) resulted in intracellular oxidative stress, lipid peroxidation, cell membrane leakage, and oxidative DNA damage. The protective effect of N-acetylcysteine on ZnO-induced cytotoxicity further implicated oxidative stress in the cytotoxicity. Free Zn2+ and metal impurities were not major contributors of ROS induction as indicated by limited free Zn2+ cytotoxicity, extent of Zn2+ dissociation in the cell culture medium, and inductively-coupled plasma-mass spectrometry metal analysis. We conclude that (1) exposure to both sizes of ZnO particles leads to dose- and time-dependent cytotoxicity reflected in oxidative stress, lipid peroxidation, cell membrane damage, and oxidative DNA damage, (2) ZnO particles exhibit a much steeper dose-response pattern unseen in other metal oxides, and (3) neither free Zn2+ nor metal impurity in the ZnO particle samples is the cause of cytotoxicity.

The analyze of lung’s GSH number in rats exposed by cigarette smoke and inducted by rambutan peel extract

NASA Astrophysics Data System (ADS)

Lisdiana

2018-03-01

The cigarette smoke is one of the pollutants in human and environment. It contains free radical compounds which cause oxidative stress. In the oxidative stress condition, the free radical causing peroxidation of cell membrane lipid as well as damages the cell membrane. One of the biomarkers of oxidative stress happens the number of GSH. The purpose of this study was to analyze the amount of rat's GSH which exposed by cigarette smoke as well as inducted by rambutan pell extract. This study applied to 25 male rats of Wistar which divided into five groups; K1 (control), K2 (negative), K3, K4, and K5 were the treatment groups of rambutan peel extract with various dosage; 3, 6, 12 mg/200 gramBB and cigarette smoke exposure along 30 days. The number of GSH measured by the DTNB of lung tissue. To know the difference of GSH number of each group did the data analysis with one way ANOVA test and LSD advance test. The result of statistic analysis showed that there was a significant difference between the control group and treatment group. The conclusion of this study was the rambutan peel extract with 3 mg/200 gramBB dosage could increase the number of lung's GSH of rats exposed to cigarette smoke.

Evaluation of two inflow control devices for flight simulation of fan noise using a JT15D engine

NASA Technical Reports Server (NTRS)

Jones, W. L.; Mcardle, J. G.; Homyak, L.

1979-01-01

The program was developed to accurately simulate flight fan noise on ground static test stands. The results generally indicated that both the induct and external ICD's were effective in reducing the inflow turbulence and the fan blade passing frequency tone generated by the turbulence. The external ICD was essentially transparent to the propagating fan tone but the induct ICD caused attenuation under most conditions.

Preferential Inhibition of Penicillinase Induction by Oxytetracycline and Its Effect on the Penicillin Susceptibility of Staphylococci

PubMed Central

Michael, Thomas M.; Michael, J. Gabriel; Massell, Benedict F.

1967-01-01

Exposure of penicillinase-producing staphylococci to a combination of penicillin and oxytetracycline resulted in a synergistic inhibitory activity of the antibiotics on the bacteria. Oxytetracycline was employed in concentrations having little or no effect on bacterial growth. It was found that the synergistic antibacterial effect was caused by the preferential inhibition of penicillinase induction by oxytetracycline, rendering the staphylococci more susceptible to penicillin. PMID:5182245

Calcium and calmodulin are involved in blue light induction of the gsa gene for an early chlorophyll biosynthetic step in Chlamydomonas.

PubMed Central

Im, C S; Matters, G L; Beale, S I

1996-01-01

The Chlamydomonas reinhardtii nuclear gene gsa, which encodes the early chlorophyll biosynthetic enzyme glutamate 1-semialdehyde aminotransferase (GSAT), is specifically induced by blue light in cells synchronized in a 12-hr-light and 12-hr-dark regime. Light induction required the presence of a nitrogen source in the incubation medium. Maximal induction also required acetate. However, in the absence of acetate, partial induction occurred when Ca2+ was present in the medium at concentrations of > or = 1 microM. The Ca2+ channel-blocking agents Nd3+ and nifedipine partially inhibited the external Ca(2+)-supported induction of GSAT mRNA but did not inhibit acetate-supported induction. The calmodulin antagonists trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide inhibited both external Ca(2+)-supported and acetate-supported induction. The Ca2+ ionophore A23187 caused a transient induction in the dark. These results suggest that Ca2+ and calmodulin are involved in the signal transduction pathway linking blue light perception to the induction of GSAT mRNA. The electron transport uncoupler carbonyl cyanide m-chlorophenylhydrazone inhibited acetate-supported induction of GSAT mRNA but did not inhibit external Ca(2+)-supported induction. It is proposed that in the presence of acetate, an internal pool of Ca2+ can be mobilized as a second message, whereas in the absence of acetate, internal Ca2+ is not available but the requirement for Ca2+ can be partially met by an external Ca2+ source. The mobilization of internal Ca2+ may require energy derived from metabolism of acetate. PMID:8989881

Effects of dexmedetomidine on heart arrhythmia prevention in off-pump coronary artery bypass surgery: A randomized clinical trial

PubMed Central

Soltani, Ghasem; Jahanbakhsh, Saeed; Tashnizi, Mohammad Abbasi; Fathi, Mehdi; Amini, Shahram; Zirak, Nahid; Sheybani, Shima

2017-01-01

Background Arrhythmia occurring during and after surgery is one of the major complications in open-heart surgery. Dexmedetomidine is an intravenous alpha-2 agonist and very specific short-acting drug to protect the various organs against ischemic injuries and blood reflow. However, the effect of dexmedetomidine for preventing intraoperative heart arrhythmias has not been recognized. Objective This study aimed to determine the effect of dexmedetomidine on the incidence rate of heart arrhythmias and anesthetic required in off-pump coronary artery bypass surgery. Methods This randomized clinical trial was conducted on patients who were candidates for off-pump coronary artery bypass referring to Imam Reza Hospital of Mashhad, Iran, from July 2016 through January 2017. The patients were randomly assigned to two groups of intervention (infusion of 0.5 mcg/kg/h dexmedetomidine together with induction followed by infusion of 0.5 mcg/kg/h by the end of the surgery) or control (saline infusion). Mean arterial pressure (MAP) and heart rate (HR) were measured before induction, during surgery operation and ICU admission. Data were analyzed by SPSS version 18 using Chi Square and independent-samples t-test. Results A total of 76 patients with a mean age of 59.8 ± 8.2 years (in two groups of 38) were studied. The two groups had no statistically significant difference in terms of background variables. The MAP and HR values before induction, during surgery and ICU admission were significantly higher in the control group than in the intervention group (p=0.001). Out of the studied arrhythmias, the values of PAC (55.2% vs. 15.7%), PVC (81.5% vs. 21.0%), AF (26.3% vs. 7.8%), VTAC (21.0% vs. 2.6%) were significantly lower in dexmedetomidine group (p=0.001). Conclusion It seems that dexmedetomidine administration during induction and surgery can cause significant reduction in most of the common arrhythmias in off-pump coronary bypass surgery. The use of dexmedetomidine maintains MAP and HR at significantly lower values, and changes compared to the control group as well as reduces the need for anesthetic compounds. Trial Registration The present study has been registered at the Iranian Registry of Clinical Trials (www.IRCT.IR) with a code of IRCT2016072413159N9 before starting the study. Founding This study was fully sponsored by the Research Deputy at Mashhad University of Medical Sciences, Iran (grant number 941413). PMID:29238500

Non-pharmacological interventions for assisting the induction of anaesthesia in children.

PubMed

Manyande, Anne; Cyna, Allan M; Yip, Peggy; Chooi, Cheryl; Middleton, Philippa

2015-07-14

Induction of general anaesthesia can be distressing for children. Non-pharmacological methods for reducing anxiety and improving co-operation may avoid the adverse effects of preoperative sedation. To assess the effects of non-pharmacological interventions in assisting induction of anaesthesia in children by reducing their anxiety, distress or increasing their co-operation. In this updated review we searched CENTRAL (the Cochrane Library 2012, Issue 12) and searched the following databases from inception to 15 January 2013: MEDLINE, EMBASE, PsycINFO and Web of Science. We reran the search in August 2014. We will deal with the single study found to be of interest when we next update the review. We included randomized controlled trials of a non-pharmacological intervention implemented on the day of surgery or anaesthesia. At least two review authors independently extracted data and assessed risk of bias in trials. We included 28 trials (2681 children) investigating 17 interventions of interest; all trials were conducted in high-income countries. Overall we judged the trials to be at high risk of bias. Except for parental acupuncture (graded low), all other GRADE assessments of the primary outcomes of comparisons were very low, indicating a high degree of uncertainty about the overall findings. Parental presence: In five trials (557 children), parental presence at induction of anaesthesia did not reduce child anxiety compared with not having a parent present (standardized mean difference (SMD) 0.03, 95% confidence interval (CI) -0.14 to 0.20). In a further three trials (267 children) where we were unable to pool results, we found no clear differences in child anxiety, whether a parent was present or not. In a single trial, child anxiety showed no significant difference whether one or two parents were present, although parental anxiety was significantly reduced when both parents were present at the induction. Parental presence was significantly less effective than sedative premedication in reducing children's anxiety at induction in three trials with 254 children (we could not pool results). Child interventions (passive): When a video of the child's choice was played during induction, children were significantly less anxious than controls (median difference modified Yale Preoperative Anxiety Scale (mYPAS) 31.2, 95% CI 27.1 to 33.3) in a trial of 91 children. In another trial of 120 children, co-operation at induction did not differ significantly when a video fairytale was played before induction. Children exposed to low sensory stimulation were significantly less anxious than control children on introduction of the anaesthesia mask and more likely to be co-operative during induction in one trial of 70 children. Music therapy did not show a significant effect on children's anxiety in another trial of 51 children. Child interventions (mask introduction): We found no significant differences between a mask exposure intervention and control in a single trial of 103 children for child anxiety (risk ratio (RR) 0.59, 95% CI 0.31 to 1.11) although children did demonstrate significantly better co-operation in the mask exposure group (RR 1.27, 95% CI 1.06 to 1.51). Child interventions (interactive): In a three-arm trial of 168 children, preparation with interactive computer packages (in addition to parental presence) was more effective than verbal preparation, although differences between computer and cartoon preparation were not significant, and neither was cartoon preparation when compared with verbal preparation. Children given video games before induction were significantly less anxious at induction than those in the control group (mYPAS mean difference (MD) -9.80, 95% CI -19.42 to -0.18) and also when compared with children who were sedated with midazolam (mYPAS MD -12.20, 95% CI -21.82 to -2.58) in a trial of 112 children. When compared with parental presence only, clowns or clown doctors significantly lessened children's anxiety in the operating/induction room (mYPAS MD -24.41, 95% CI -38.43 to -10.48; random-effects, I² 75%) in three trials with a total of 133 children. However, we saw no significant differences in child anxiety in the operating room between clowns/clown doctors and sedative premedication (mYPAS MD -9.67, 95% CI -21.14 to 1.80, random-effects, I² 66%; 2 trials of 93 children). In a trial of hypnotherapy versus sedative premedication in 50 children, there were no significant differences in children's anxiety at induction (RR 0.59, 95% CI 0.33 to 1.04). Parental interventions: Children of parents having acupuncture compared with parental sham acupuncture were less anxious during induction (mYPAS MD -17, 95% CI -30.51 to -3.49) and were more co-operative (RR 1.59, 95% CI 1.01 to 2.53) in a single trial of 67 children. Two trials with 191 parents assessed the effects of parental video viewing but did not report any of the review's prespecified primary outcomes. This review shows that the presence of parents during induction of general anaesthesia does not diminish their child's anxiety. Potentially promising non-pharmacological interventions such as parental acupuncture; clowns/clown doctors; playing videos of the child's choice during induction; low sensory stimulation; and hand-held video games need further investigation in larger studies.

Transvaginal ultrasonographic cervical measurement in predicting failed labor induction and cesarean delivery for failure to progress in nulliparous women.

PubMed

Park, Kyo Hoon

2007-08-01

The aim of this study was to evaluate the value of transvaginal sonographic cervical measurement in predicting failed labor induction and cesarean delivery for failure to progress in nulliparous women. One hundred and sixty-one women scheduled for labor induction underwent transvaginal ultrasonography and digital cervical examinations. Logistic regression demonstrated that cervical length and gestational age at induction, but not the Bishop score, significantly and independently predicted failed labor induction. According to the receiver operating characteristic curves analysis, the best cut-off value of cervical length for predicting failed labor induction was 28 mm, with a sensitivity of 62% and a specificity of 60%. In terms of the likelihood of a cesarean delivery for failure to progress as the outcome variable, logistic regression indicated that maternal height and birth weight, but not cervical length or Bishop score, were significantly and independently associated with an increased risk of cesarean delivery for failure to progress. Transvaginal sonographic measurements of cervical length thus independently predicted failed labor induction in nulliparous women. However, the relatively poor predictive performance of this test undermines its clinical usefulness as a predictor of failed labor induction. Moreover, cervical length appears to have a poor predictive value for the likelihood of a cesarean delivery for failure to progress.

PROTECTIVE EFFECT OF MORINGA PEREGRINA LEAVES EXTRACT ON ACETAMINOPHEN -INDUCED LIVER TOXICITY IN ALBINO RATS.

PubMed

Azim, Samy Abdelfatah Abdel; Abdelrahem, Mohamed Taha; Said, Mostafa Mohamed; Khattab, Alshaimaa

2017-01-01

Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. Induction of hepatotoxicity was done by chronic oral administration of acetaminophen (750 mg/kg bwt) for 4 weeks. To study the possible hepatoprotective effect, Moringa peregrina leaves extract (200 mg/kg bwt) or Silymarin (50 mg/kg bwt) was administered orally, for 4 weeks, along with acetaminophen. acetaminophen significantly increased serum liver enzymes and caused oxidative stress, evidenced by significantly increased tissue malondialdehyde, glutathione peroxidase, hepatic DNA fragmentation, and significant decrease of glutathione and antioxidant enzymes in liver, blood and brain. On the other hand, administration of Moringa peregrina leaves extract reversed acetaminophen-related toxic effects through: powerful malondialdehyde suppression, glutathione peroxidase normalization and stimulation of the cellular antioxidants synthesis represented by significant increase of glutathione, catalase and superoxide dismutase in liver, blood and brain, besides, DNA fragmentation was significantly decreased in the liver tissue. acetaminophen induced oxidative damage can be improved by Moringa peregrina leaves extract-treatment, due to its antioxidant potential.

PROTECTIVE EFFECT OF MORINGA PEREGRINA LEAVES EXTRACT ON ACETAMINOPHEN -INDUCED LIVER TOXICITY IN ALBINO RATS

PubMed Central

Azim, Samy Abdelfatah Abdel; Abdelrahem, Mohamed Taha; Said, Mostafa Mohamed; khattab, Alshaimaa

2017-01-01

Background: Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. Materials and methods: Induction of hepatotoxicity was done by chronic oral administration of acetaminophen (750 mg/kg bwt) for 4 weeks. To study the possible hepatoprotective effect, Moringa peregrina leaves extract (200 mg/kg bwt) or Silymarin (50 mg/kg bwt) was administered orally, for 4 weeks, along with acetaminophen. Results: acetaminophen significantly increased serum liver enzymes and caused oxidative stress, evidenced by significantly increased tissue malondialdehyde, glutathione peroxidase, hepatic DNA fragmentation, and significant decrease of glutathione and antioxidant enzymes in liver, blood and brain. On the other hand, administration of Moringa peregrina leaves extract reversed acetaminophen-related toxic effects through: powerful malondialdehyde suppression, glutathione peroxidase normalization and stimulation of the cellular antioxidants synthesis represented by significant increase of glutathione, catalase and superoxide dismutase in liver, blood and brain, besides, DNA fragmentation was significantly decreased in the liver tissue. Conclusion: acetaminophen induced oxidative damage can be improved by Moringa peregrina leaves extract-treatment, due to its antioxidant potential. PMID:28573237

Beam control in the ETA-II linear induction accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yu-Jiuan

1992-08-21

Corkscrew beam motion is caused by chromatic aberration and misalignment of a focusing system. We have taken some measures to control the corkscrew motion on the ETA-11 induction accelerator. To minimize chromatic aberration, we have developed an energy compensation scheme which reduces energy sweep and differential phase advance within a beam pulse. To minimize the misalignment errors, we have developed a time-independent steering algorithm which minimizes the observed corkscrew amplitude averaged over the beam pulse. The steering algorithm can be used even if the monitor spacing is much greater than the system`s cyclotron wavelength and the corkscrew motion caused bymore » a given misaligned magnet is fully developed, i.e., the relative phase advance is greater than 27{pi}.« less

Beam control in the ETA-II linear induction accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yu-Jiuan.

1992-08-21

Corkscrew beam motion is caused by chromatic aberration and misalignment of a focusing system. We have taken some measures to control the corkscrew motion on the ETA-11 induction accelerator. To minimize chromatic aberration, we have developed an energy compensation scheme which reduces energy sweep and differential phase advance within a beam pulse. To minimize the misalignment errors, we have developed a time-independent steering algorithm which minimizes the observed corkscrew amplitude averaged over the beam pulse. The steering algorithm can be used even if the monitor spacing is much greater than the system's cyclotron wavelength and the corkscrew motion caused bymore » a given misaligned magnet is fully developed, i.e., the relative phase advance is greater than 27[pi].« less

Caco-2 cells - expression, regulation and function of drug transporters compared with human jejunal tissue.

PubMed

Brück, S; Strohmeier, J; Busch, D; Drozdzik, M; Oswald, S

2017-03-01

Induction or inhibition of drug transporting proteins by concomitantly administered drugs can cause serious drug-drug interactions (DDIs). However, in vitro assays currently available are mostly for studying the inhibitory potential of drugs on intestinal transporter proteins, rather than induction. Therefore, this study investigated the suitability of the frequently used intestinal Caco-2 cell line to predict transporter-mediated DDIs as caused by induction via activation of nuclear receptors. TaqMan® low density arrays and LC-MS/MS based targeted proteomics were used to evaluate transporter expression in Caco-2 cells in comparison with jejunal tissue, in culture-time dependence studies and after incubation with different known inducers of drug metabolism and transport. Additionally, studies on ABCB1 function were performed using Transwell® assays with [ 3 H]-digoxin and [ 3 H]-talinolol as substrates after incubation with the prototypical inducers rifampicin, St John's wort, carbamazepine and efavirenz. The gene and protein expression pattern of drug transporters in Caco-2 cells and jejunal tissue differed considerably. For some transporters culture-time dependent differences in mRNA expression and/or protein abundance could be determined. Finally, none of the studied prototypical inducers showed an effect either on mRNA expression and protein abundance or on the function of ABCB1. Differences in transporter expression in Caco-2 cells compared with jejunal tissue, as well as expression dependence on culture time must be considered in in vitro studies to avoid under- or overestimation of certain transporters. The Caco-2 cell model is not suitable for the evaluation of DDIs caused by transporter induction. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training.

PubMed

Williams, N I; Helmreich, D L; Parfitt, D B; Caston-Balderrama, A; Cameron, J L

2001-11-01

Cross-sectional and short-term prospective studies in humans support the concept that low energy availability, and not other factors associated with exercise, causes the development of exercise-induced reproductive dysfunction. To rigorously test this hypothesis, we performed a longitudinal study, examining the role of low energy availability on both the development and the reversal of exercise-induced amenorrhea, using a monkey model (Macaca fascicularis). Eight adult female monkeys developed amenorrhea (defined as absence of menses for at least 100 d, with low and unchanging concentrations of LH, FSH, E2, and P4) after gradually increasing their daily exercise to 12.3 +/- 0.9 km/d of running over a 7- to 24-month period. Food intake remained constant during exercise training. To test whether amenorrhea is caused by low energy availability, four of the eight amenorrheic monkeys were provided with supplemental calories (138-181% of calorie intake during amenorrhea) while they maintained their daily training. All four monkeys exhibited increased reproductive hormone levels and reestablished ovulatory cycles, with recovery times for circulating gonadotropin levels ranging from 12-57 d from the initiation of supplemental feeding. The rapidity of recovery within the reproductive axis in a given monkey was directly related to the amount of energy that was consumed during the period of supplemental feeding (r = -0.97; P < 0.05). Repeated measurements of plasma T3 concentrations, a marker of cellular energy availability, revealed a tight correlation between the changes in reproductive function and T3 levels, such that T3 significantly decreased (27%) with the induction and significantly increased (18%) with the reversal of amenorrhea (P < 0.05). These data provide strong evidence that low energy availability plays a causal role in the development of exercise-induced amenorrhea.

Morus alba Leaf Lectin (MLL) Sensitizes MCF-7 Cells to Anoikis by Inhibiting Fibronectin Mediated Integrin-FAK Signaling through Ras and Activation of P38 MAPK

PubMed Central

Saranya, Jayaram; Shilpa, Ganesan; Raghu, Kozhiparambil G.; Priya, Sulochana

2017-01-01

Lectins are a unique class of carbohydrate binding proteins/glycoproteins, and many of them possess anticancer properties. They can induce cell cycle arrest and apoptosis, inhibit protein synthesis, telomerase activity and angiogenesis in cancer cells. In the present study, we have demonstrated the effect of Morus alba leaf lectin (MLL) on anoikis induction in MCF-7 cells. Anoikis induction in cancer cells has a significant role in preventing early stage metastasis. MLL treatment in monolayers of MCF-7 cells caused significant detachment of cells in a time and concentration dependent manner. The detached cells failed to re-adhere and grew even to culture plates coated with different matrix proteins. DNA fragmentation, membrane integrity studies, annexin V staining, caspase 9 activation and upregulation of Bax/Bad confirmed that the detached cells underwent apoptosis. Upregulation of matrix metalloproteinase 9 (MMP-9) caused a decrease in fibronectin (FN) production which facilitated the cells to detach by blocking the FN mediated downstream signaling. On treatment with MLL, we have observed downregulation of integrin expression, decreased phosphorylation of focal adhesion kinase (FAK), loss in FAK-integrin interaction and active Ras. MLL treatment downregulated the levels of phosphorylated Akt and PI3K. Also, we have studied the effect of MLL on two stress activated protein kinases p38 MAPK and JNK. p38 MAPK activation was found to be elevated, but there was no change in the level of JNK. Thus our study substantiated the possible antimetastatic effect of MLL by inducing anoikis in MCF-7 cells by activation of caspase 9 and proapoptotic Bax/Bad by blockage of FN mediated integrin/FAK signaling and partly by activation of p38 MAPK. PMID:28223935

An organ-specific role for ethylene in rose petal expansion during dehydration and rehydration

PubMed Central

Liu, Daofeng; Liu, Xiaojing; Meng, Yonglu; Sun, Cuihui; Tang, Hongshu; Jiang, Yudong; Khan, Muhammad Ali; Xue, Jingqi; Ma, Nan; Gao, Junping

2013-01-01

Dehydration is a major factor resulting in huge loss from cut flowers during transportation. In the present study, dehydration inhibited petal cell expansion and resulted in irregular flowers in cut roses, mimicking ethylene-treated flowers. Among the five floral organs, dehydration substantially elevated ethylene production in the sepals, whilst rehydration caused rapid and elevated ethylene levels in the gynoecia and sepals. Among the five ethylene biosynthetic enzyme genes (RhACS1–5), expression of RhACS1 and RhACS2 was induced by dehydration and rehydration in the two floral organs. Silencing both RhACS1 and RhACS2 significantly suppressed dehydration- and rehydration-induced ethylene in the sepals and gynoecia. This weakened the inhibitory effect of dehydration on petal cell expansion. β-glucuronidase activity driven by both the RhACS1 and RhACS2 promoters was dramatically induced in the sepals, pistil, and stamens, but not in the petals of transgenic Arabidopsis. This further supports the organ-specific induction of these two genes. Among the five rose ethylene receptor genes (RhETR1–5), expression of RhETR3 was predominantly induced by dehydration and rehydration in the petals. RhETR3 silencing clearly aggravated the inhibitory effect of dehydration on petal cell expansion. However, no significant difference in the effect between RhETR3-silenced flowers and RhETR-genes-silenced flowers was observed. Furthermore, RhETR-genes silencing extensively altered the expression of 21 cell expansion-related downstream genes in response to ethylene. These results suggest that induction of ethylene biosynthesis by dehydration proceeds in an organ-specific manner, indicating that ethylene can function as a mediator in dehydration-caused inhibition of cell expansion in rose petals. PMID:23599274

Endothelin antagonism in portal hypertensive mice: implications for endothelin receptor-specific signaling in liver disease

PubMed Central

Feng, Hong-Qiang; Weymouth, Nate D.; Rockey, Don C.

2009-01-01

Endothelin-1 (ET-1), a potent vasoactive peptide, plays an important role in the pathogenesis of liver disease and portal hypertension. Two major endothelin receptors (ET-A and ET-B) mediate biological effects, largely on the basis of their known downstream signaling pathways. We hypothesized that the different receptors are likely to mediate divergent effects in portal hypertensive mice. Liver fibrosis and cirrhosis and portal hypertension were induced in 8-wk-old male BALB/c mice by gavage with carbon tetrachloride (CCl4). Portal pressure was recorded acutely during intravenous infusion of endothelin receptor antagonists in normal or portal hypertensive mice. In vivo microscopy was used to monitor sinusoidal dynamics. Additionally, the effect of chronic exposure to endothelin antagonists was assessed in mice during induction of fibrosis and cirrhosis with CCl4 for 8 wk. Intravenous infusion of ET-A receptor antagonists into normal and cirrhotic mice reduced portal pressure whereas ET-B receptor antagonism increased portal pressure. A mixed endothelin receptor antagonist also significantly reduced portal pressure. Additionally, the ET-A receptor antagonist caused sinusoidal dilation, whereas the ET-B receptor antagonist caused sinusoidal constriction. Chronic administration of each the endothelin receptor antagonists during the induction of fibrosis and portal hypertension led to reduced fibrosis, a significant reduction in portal pressure, and altered sinusoidal dynamics relative to controls. Acute effects of endothelin receptor antagonists are likely directly on the hepatic and sinusoidal vasculature, whereas chronic endothelin receptor antagonism appears to be more complicated, likely affecting fibrogenesis and the hepatic microcirculation. The data imply a relationship between hepatic fibrogenesis or fibrosis and vasomotor responses. PMID:19299580

Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival

PubMed Central

Thole, Theresa M; Lodrini, Marco; Fabian, Johannes; Wuenschel, Jasmin; Pfeil, Sebastian; Hielscher, Thomas; Kopp-Schneider, Annette; Heinicke, Ulrike; Fulda, Simone; Witt, Olaf; Eggert, Angelika; Fischer, Matthias; Deubzer, Hedwig E

2017-01-01

The number of long-term survivors of high-risk neuroblastoma remains discouraging, with 10-year survival as low as 20%, despite decades of considerable international efforts to improve outcome. Major obstacles remain and include managing resistance to induction therapy, which causes tumor progression and early death in high-risk patients, and managing chemotherapy-resistant relapses, which can occur years after the initial diagnosis. Identifying and validating novel therapeutic targets is essential to improve treatment. Delineating and deciphering specific functions of single histone deacetylases in neuroblastoma may support development of targeted acetylome-modifying therapeutics for patients with molecularly defined high-risk neuroblastoma profiles. We show here that HDAC11 depletion in MYCN-driven neuroblastoma cell lines strongly induces cell death, mostly mediated by apoptotic programs. Genes necessary for mitotic cell cycle progression and cell division were most prominently enriched in at least two of three time points in whole-genome expression data combined from two cell systems, and all nine genes in these functional categories were strongly repressed, including CENPA, KIF14, KIF23 and RACGAP1. Enforced expression of one selected candidate, RACGAP1, partially rescued the induction of apoptosis caused by HDAC11 depletion. High-level expression of all nine genes in primary neuroblastomas significantly correlated with unfavorable overall and event-free survival in patients, suggesting a role in mediating the more aggressive biological and clinical phenotype of these tumors. Our study identified a group of cell cycle-promoting genes regulated by HDAC11, being both predictors of unfavorable patient outcome and essential for tumor cell viability. The data indicate a significant role of HDAC11 for mitotic cell cycle progression and survival of MYCN-amplified neuroblastoma cells, and suggests that HDAC11 could be a valuable drug target. PMID:28252645

The pathogenesis of diclofenac induced immunoallergic hepatitis in a canine model of liver injury

PubMed Central

Selvaraj, Saravanakumar; Oh, Jung-Hwa; Spanel, Reinhard; Länger, Florian; Han, Hyoung-Yun; Lee, Eun-Hee; Yoon, Seokjoo; Borlak, Jürgen

2017-01-01

Hypersensitivity to non-steroidal anti-inflammatory drugs is a common adverse drug reaction and may result in serious inflammatory reactions of the liver. To investigate mechanism of immunoallergic hepatitis beagle dogs were given 1 or 3 mg/kg/day (HD) oral diclofenac for 28 days. HD diclofenac treatment caused liver function test abnormalities, reduced haematocrit and haemoglobin but induced reticulocyte, WBC, platelet, neutrophil and eosinophil counts. Histopathology evidenced hepatic steatosis and glycogen depletion, apoptosis, acute lobular hepatitis, granulomas and mastocytosis. Whole genome scans revealed 663 significantly regulated genes of which 82, 47 and 25 code for stress, immune response and inflammation. Immunopathology confirmed strong induction of IgM, the complement factors C3&B, SAA, SERPING1 and others of the classical and alternate pathway. Alike, marked expression of CD205 and CD74 in Kupffer cells and lymphocytes facilitate antigen presentation and B-cell differentiation. The highly induced HIF1A and KLF6 protein expression in mast cells and macrophages sustain inflammation. Furthermore, immunogenomics discovered 24, 17, 6 and 11 significantly regulated marker genes to hallmark M1/M2 polarized macrophages, lymphocytic and granulocytic infiltrates; note, the latter was confirmed by CAE staining. Other highly regulated genes included alpha-2-macroglobulin, CRP, hepcidin, IL1R1, S100A8 and CCL20. Diclofenac treatment caused unprecedented induction of myeloperoxidase in macrophages and oxidative stress as shown by SOD1/SOD2 immunohistochemistry. Lastly, bioinformatics defined molecular circuits of inflammation and consisted of 161 regulated genes. Altogether, the mechanism of diclofenac induced liver hypersensitivity reactions involved oxidative stress, macrophage polarization, mastocytosis, complement activation and an erroneous programming of the innate and adaptive immune system. PMID:29296203

The small-molecule kinase inhibitor D11 counteracts 17-AAG-mediated up-regulation of HSP70 in brain cancer cells

PubMed Central

Schaefer, Susanne; Svenstrup, Tina H.

2017-01-01

Many types of cancer express high levels of heat shock proteins (HSPs) that are molecular chaperones regulating protein folding and stability ensuring protection of cells from potentially lethal stress. HSPs in cancer cells promote survival, growth and spreading even in situations of growth factors deprivation by associating with oncogenic proteins responsible for cell transformation. Hence, it is not surprising that the identification of potent inhibitors of HSPs, notably HSP90, has been the primary research focus, in recent years. Exposure of cancer cells to HSP90 inhibitors, including 17-AAG, has been shown to cause resistance to chemotherapeutic treatment mostly attributable to induction of the heat shock response and increased cellular levels of pro-survival chaperones. In this study, we show that treatment of glioblastoma cells with 17-AAG leads to HSP90 inhibition indicated by loss of stability of the EGFR client protein, and significant increase in HSP70 expression. Conversely, co-treatment with the small-molecule kinase inhibitor D11 leads to suppression of the heat shock response and inhibition of HSF1 transcriptional activity. Beside HSP70, Western blot and differential mRNA expression analysis reveal that combination treatment causes strong down-regulation of the small chaperone protein HSP27. Finally, we demonstrate that incubation of cells with both agents leads to enhanced cytotoxicity and significantly high levels of LC3-II suggesting autophagy induction. Taken together, results reported here support the notion that including D11 in future treatment regimens based on HSP90 inhibition can potentially overcome acquired resistance induced by the heat shock response in brain cancer cells. PMID:28542269

Group Hypnotizability Of Inpatient Adolescents.

PubMed

Quant, Michael; Schilder, Steffanie; Sapp, Marty; Zhang, Bo; Baskin, Thomas; Arndt, Leah Rouse

2017-01-01

This study investigated group hypnotizability in 167 adolescents (ages 13-17) in an inpatient behavioral healthcare setting through use of the Waterloo-Stanford Group Scale, Form C. It also investigated the influence of hypnotic inductions on group hypnotizability. Adolescents were randomly assigned to either a group session of hypnosis (n = 84) with a hypnotic induction or a comparison "no-induction" group (n = 83) that received identical suggestions without a hypnotic induction. Adolescents' imaginative absorption and dissociation were measured to examine their influence on hypnotizability. A between-group comparison showed the induction condition had a significantly higher score than the no-induction group on both behavioral and subjective measures of hypnotizability.

Administration of human recombinant activated protein C is not associated with pancreatic parenchymal haemorrhage in L-arginine-induced experimental acute pancreatitis.

PubMed

Jamdar, Saurabh; Babu, Benoy I; Nirmalan, Mahesh; Jeziorska, Maria; McMahon, Raymond F T; Siriwardena, Ajith K

2013-11-10

Microvascular thrombosis is a critical event in severe acute pancreatitis. Human recombinant activated protein C (Xigris®, Eli Lilly, Indianapolis, IN, USA) modulates the interplay between pro-inflammatory and pro-coagulant pathways and maintains microvascular patency. However, the anticoagulant properties of Xigris® may precipitate bleeding from the inflamed pancreas. This study tests the hypothesis that Xigris® can ameliorate experimental acute pancreatitis without causing pancreatic haemorrhage. Sprague Dawley rats were allocated as follows: Group 1: control (n=7); Group 2: acute pancreatitis (n=6); Group 3: administration of Xigris® 500 µg/kg body weight before induction of acute pancreatitis (n=6); and Group 4: Administration of Xigris® 500 µg/kg body weight 30 minutes after induction of acute pancreatitis (n=6). Acute pancreatitis was induced by intraperitoneal administration of L-arginine 300 mg/100 g body weight. Animals were sacrificed at 48 hours and biochemical, haematological, and histological markers of pancreatic haemorrhage and inflammation assessed. Median lipase in animals with acute pancreatitis was 10 U/mL (range: 7-16 U/mL) compared to 5.5 (range: 3-8 U/mL) in controls (P=0.028). Lipase was also elevated in animals given Xigris® both before (12 U/mL, range: 8-22 U/mL; P=0.031 vs. control group) and after (46 U/mL, range: 9-71 U/mL; P=0.015 vs. control group) induction of acute pancreatitis). Haemoglobin levels were similar among all groups (P=0.323). There was no histological evidence of pancreatic haemorrhage in animals treated with Xigris®. Pre-treatment with Xigris® was associated with a significant reduction in pancreatic injury. This effect was absent when Xigris® was administered after induction of acute pancreatitis. Xigris® did not lead to pancreatic haemorrhage in experimental acute pancreatitis. Administration of Xigris® prior to induction of acute pancreatitis was associated with amelioration of injury. This effect was not seen with administration of Xigris® after induction of acute pancreatitis.

THR-18, a 18-mer peptide derived from PAI-1, is neuroprotective and improves thrombolysis by tPA in rat stroke models.

PubMed

Krakovsky, M; Polianski, V; Nimrod, A; Higazi, A; Leker, R R; Lamensdorf, I

2011-11-01

The thrombolytic treatment of stroke is limited by a narrow therapeutic time window and is associated with significant adverse side effects. To improve this situation, the modulation of tissue-type plasminogen activator (tPA) activity by a synthetic plasminogen activator inhibitor-1-derived 18-mer peptide (THR-18) was examined in two models of stroke in rats. In the first model (thromboembolic), stroke was induced by intra-carotid injection of micro-clots to rats, and tPA (6 mg/kg) was intravenously infused for 30 minutes with or without THR-18 (1 mg/kg) at 4 hours post-induction. In the second model [transient middle cerebral artery occlusion (tMCAO)], stroke was induced for 2 hours by a transient mechanical occlusion. tPA and/or THR-18 (0.02, 0.1, and 1 mg/kg) were intravenously infused for 60 minutes at the time of reperfusion. In the thromboembolic model, cerebral blood flow, measured before and up to 5.5 hours post-induction, revealed that tPA administration caused reperfusion of flow at 30 minutes post-infusion. Later on, an additional increase in reperfusion was seen in the tPA+THR-18 group, and not with tPA alone. In both models, the frequency of intracranial hemorrhage in the tPA-treated group was found to be significantly higher than the control, and this tPA effect was attenuated by THR-18. In the thromboembolic study, infarct size and brain edema were similar in the control and tPA-treated rats. However, the combination of tPA and THR-18 caused a statistically significant reduction in both parameters (infarct size 17.8 versus 25.0%, brain edema 5 versus 8%, tPA+THR-18 versus control, respectively). In the tMCAO mechanical model, infarct size and brain edema were both increased by tPA treatment as compared to the control group, and this increase was markedly diminished by THR-18 co-administration. Neurobehavioral assessment of the tMCAO animals performed at 72 hours post-stroke induction revealed significant improvements (P<0.05-0.01) in neuroscores in all groups of animals treated with peptide-tPA, as compared to the tPA monotherapy group. A significant (P<0.05) improvement in the neurological outcome was also seen in the THR-18 monoterapy group, as compared to the control animals, thus demonstrating a clear neuroprotective effect by the peptide on its own. The results support the use of THR-18 together with tPA in the thrombolytic therapy of stroke, in order to achieve better patency, less tPA-induced damage, and possibly a widening of tPA therapeutic time window.

Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles

PubMed Central

Alarifi, Saud; Ali, Daoud; Alkahtani, Saad; Verma, Ankit; Ahamed, Maqusood; Ahmed, Mukhtar; Alhadlaq, Hisham A

2013-01-01

The widespread use of zinc oxide (ZnO) nanoparticles worldwide exposes humans to their adverse effects, so it is important to understand their biological effects and any associated risks. This study was designed to investigate the cytotoxicity, oxidative stress, and apoptosis caused by ZnO nanoparticles in human skin melanoma (A375) cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] and lactate dehydrogenase-based cell viability assays showed a significant decrease in cell viability after exposure to ZnO nanoparticles, and phase contrast images revealed that cells treated with these nanoparticles had a lower density and a rounded morphology. ZnO nanoparticles were also found to induce oxidative stress, evidenced by generation of reactive oxygen species and depletion of the antioxidant, glutathione. Induction of apoptosis was confirmed by chromosomal condensation assay and caspase-3 activation. Further, more DNA damage was observed in cells exposed to the highest concentration of ZnO nanoparticles. These results demonstrate that ZnO nanoparticles have genotoxic potential in A375 cells, which may be mediated via oxidative stress. Our short-term exposure study showing induction of a genotoxic and apoptotic response to ZnO nanoparticles needs further investigation to determine whether there may be consequences of long-term exposure to ZnO nanoparticles. PMID:23493450

Deletion analysis of Streptococcus pneumoniae late competence genes distinguishes virulence determinants that are dependent or independent of competence induction.

PubMed

Zhu, Luchang; Lin, Jingjun; Kuang, Zhizhou; Vidal, Jorge E; Lau, Gee W

2015-07-01

The competence regulon of Streptococcus pneumoniae (pneumococcus) is crucial for genetic transformation. During competence development, the alternative sigma factor ComX is activated, which in turn, initiates transcription of 80 'late' competence genes. Interestingly, only 16 late genes are essential for genetic transformation. We hypothesized that these late genes that are dispensable for competence are beneficial to pneumococcal fitness during infection. These late genes were systematically deleted, and the resulting mutants were examined for their fitness during mouse models of bacteremia and acute pneumonia. Among these, 14 late genes were important for fitness in mice. Significantly, deletion of some late genes attenuated pneumococcal fitness to the same level in both wild-type and ComX-null genetic backgrounds, suggesting that the constitutive baseline expression of these genes was important for bacterial fitness. In contrast, some mutants were attenuated only in the wild-type genetic background but not in the ComX-null background, suggesting that specific expression of these genes during competence state contributed to pneumococcal fitness. Increased virulence during competence state was partially caused by the induction of allolytic enzymes that enhanced pneumolysin release. These results distinguish the role of basal expression versus competence induction in virulence functions encoded by ComX-regulated late competence genes. © 2015 John Wiley & Sons Ltd.

Sensitization of thermotolerant SCK cells to hyperthermia and freezing with reduction of intracellular pH: implications for cryosurgery.

PubMed

Burgher, Abram H; Swanlund, David J; Griffin, Robert J; Song, Chang W; Bischof, John C; Roberts, Kenneth P

2003-03-01

During cryosurgery, cells frozen slowly at the outer part of the ice ball undergo severe dehydration and are subject to solute effects injury, which may be caused in part by protein denaturation. This study was undertaken to determine whether heat shock proteins (HSPs), the molecular chaperones that stabilize proteins against denaturation, have a protective effect on cells during slow freezing. In addition, we aimed to determine whether acidic conditions, similar to those found in many solid tumors, would effect this protection. SCK cells were frozen at 5 degrees C/min to -10 degrees C or -20 degrees C before or after induction of thermotolerance, and at neutral or low pH conditions. Lethal damage was determined by clonogenics. Clonogenic survival was decreased by 50% in thermotolerant cells frozen to -10 degrees C after culture in acidic conditions (pH 6.6) compared with non-thermotolerant cells cultured at neutral pH. Induction of thermotolerance alone or low pH alone did not significantly sensitize SCK cells to freezing. All treatment groups were equally susceptible to killing when frozen to -20 degrees C. Our results show that induction of thermal tolerance does not protect SCK cells against subsequent freezing injury and that a low pH environment actually sensitizes these cells to freeze injury. Copyright 2003 Wiley-Liss, Inc.

[Clinical evaluation of propess for induction of term pregnancy].

PubMed

Gai, Ming-ying; Zhang, Jian-ping; Li, Yang; Han, Hong-jing; Yang, Jian-qiu; Wang, Shan-mi; Su, Qi-feng; Wu, Lian-fang

2003-04-01

To explore the efficacy and safety of continuously released prostaglandin E(2) (PGE(2)) suppository-propess used for induction of term pregnancy. A multicenter, prospective, case control clinical study was carried out, propess was used in 100 cases as study group, the suppository without PGE(2) was used in 49 cases as control group. The cervical maturity (by Bishop scoring), the time to labor starting, membrane rupture and delivery, the application of oxytocin, ceserean section rate, fetal and neonatal condition were compared between 2 groups after inserting of the suppository. At the same time, side effects caused by propess were investigated. Bishop score was increased >or= 2 points in 93% cases, >or= 3 points in 87% cases in study group, whereas only 4% cases whose Bishop score increased >or= 2 points in control group. The time to labor starting, membrane rupture, and delivery was shortened obviously in study group than that in control group after inserting suppository. The application of oxytocin was much less in study group, cesarean section rate was reduced in study group (32% vs 61%). There was no significant difference between 2 groups in fetal and neonatal conditions. The overstimulation of uterine contraction and mild gastrointestinal tract reaction occurred in 3 cases and 2 cases respectively in study groups. Propess can be used for induction of term pregnancy effectively and safely.

Sequential induction of prostaglandin E and D synthases in inflammation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schuligoi, Rufina; Grill, Magdalena; Heinemann, Akos

Enhanced biosynthesis of prostaglandin (PG)D{sub 2} and subsequent formation of 15-deoxy-{delta}{sup 12,14}-PGJ{sub 2} has been suggested to contribute to resolution of inflammation. The primary aim of the present study in mouse heart was, therefore, to determine at the transcriptional level if there is sequential induction of PGE and PGD synthases (S) during inflammation. Expression of interleukin (IL)-1{beta} in heart was enhanced 4 h after systemic inflammation and declined thereafter within 3-5 days to basal levels. In contrast to cyclooxygenase-2 and membrane-bound (m)-PGES-1, which both peaked 4 h after endotoxin administration, hematopoietic (H)-PGDS expression was enhanced only 48 h after endotoxin.more » The expression of lipocalin-type (L)-PGDS was not significantly influenced. mRNA encoding the putative target of 15-deoxy-{delta}{sup 12,14}-PGJ{sub 2}, peroxisome proliferator-activated receptor {gamma}, was enhanced between 4 and 24 h after induction of inflammation. Treatment of mice with acetylsalicylic acid or indomethacin at doses effective to cause near-complete inhibition of PGE{sub 2} and PGD{sub 2} biosynthesis in heart ex vivo resulted in enhanced expression of IL-1{beta} 24 h after endotoxin administration. These results provide additional support for the hypothesis of a shift towards PGD{sub 2} biosynthesis during resolution of inflammation.« less

The interaction of affective with psychotic processes: A test of the effects of worrying on working memory, jumping to conclusions, and anomalies of experience in patients with persecutory delusions

PubMed Central

Freeman, Daniel; Startup, Helen; Dunn, Graham; Černis, Emma; Wingham, Gail; Pugh, Katherine; Cordwell, Jacinta; Kingdon, David

2013-01-01

Worry has traditionally been considered in the study of common emotional disorders such as anxiety and depression, but recent studies indicate that worry may be a causal factor in the occurrence and persistence of persecutory delusions. The effect of worry on processes traditionally associated with psychosis has not been tested. The aim of the study was to examine the short-term effects of a bout of worry on three cognitive processes typically considered markers of psychosis: working memory, jumping to conclusions, and anomalous internal experience. Sixty-seven patients with persecutory delusions in the context of a non-affective psychotic disorder were randomised to a worry induction, a worry reduction, or a neutral control condition. They completed tests of the cognitive processes before and after the randomisation condition. The worry induction procedure led to a significant increase in worry. The induction of worry did not affect working memory or jumping to conclusions, but it did increase a range of mild anomalous experiences including feelings of unreality, perceptual alterations, and temporal disintegration. Worry did not affect the occurrence of hallucinations. The study shows that a period of worry causes a range of subtle odd perceptual disturbances that are known to increase the likelihood of delusions. It demonstrates an interaction between affective and psychotic processes in patients with delusions. PMID:23871449

Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice.

PubMed

Riezzo, Irene; Turillazzi, Emanuela; Bello, Stefania; Cantatore, Santina; Cerretani, Daniela; Di Paolo, Marco; Fiaschi, Anna Ida; Frati, Paola; Neri, Margherita; Pedretti, Monica; Fineschi, Vittorio

2014-10-01

Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

Sequential colonization of periodontal pathogens in induction of periodontal disease and atherosclerosis in LDLRnull mice.

PubMed

Chukkapalli, Sasanka S; Easwaran, Meena; Rivera-Kweh, Mercedes F; Velsko, Irina M; Ambadapadi, Sriram; Dai, Jiayin; Larjava, Hannu; Lucas, Alexandra R; Kesavalu, Lakshmyya

2017-01-01

Periodontal disease (PD) and atherosclerotic vascular disease (ASVD) are both chronic inflammatory diseases with a polymicrobial etiology and have been epidemiologically associated. The purpose is to examine whether periodontal bacteria that infect the periodontium can also infect vascular tissues and enhance pre-existing early aortic atherosclerotic lesions in LDLRnull mice. Mice were orally infected with intermediate bacterial colonizer Fusobacterium nucleatum for the first 12 weeks followed by late bacterial colonizers (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) for the remaining 12 weeks mimicking the human oral microbiota ecological colonization. Genomic DNA from all four bacterial was detected in gingival plaque by PCR, consistently demonstrating infection of mouse gingival surfaces. Infected mice had significant levels of IgG and IgM antibodies, alveolar bone resorption, and showed apical migration of junctional epithelium revealing the induction of PD. These results support the ability of oral bacteria to cause PD in mice. Detection of bacterial genomic DNA in systemic organs indicates hematogenous dissemination from the gingival pockets. Bacterial infection did not alter serum lipid fractions or serum amyloid A levels and did not induce aortic atherosclerotic plaque. This is the first study examining the causal role of periodontal bacteria in induction of ASVD in LDLRnull mice. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Exploring Teacher Induction: Collaborative Self-Studies across Institutions

ERIC Educational Resources Information Center

Smith, Déirdre; Engemann, Joe

2015-01-01

Educators from eight institutions engaged in collaborative self-studies of their own practices to gain deeper insight into the significance of narrative-based writing supporting the process of teacher induction. A series of teacher induction institutes based on narrative writing processes provided the context for critical exploration of the lived…

Induction of podocyte-derived VEGF ameliorates podocyte injury and subsequent abnormal glomerular development caused by puromycin aminonucleoside.

PubMed

Ma, Ji; Matsusaka, Taiji; Yang, Hai-Chun; Zhong, Jianyong; Takagi, Nobuaki; Fogo, Agnes B; Kon, Valentina; Ichikawa, Iekuni

2011-07-01

Our previous studies using puromycin aminonucleoside (PAN) established that podocyte damage leads to glomerular growth arrest during development and glomerulosclerosis later in life. This study examined the potential benefit of maintaining podocyte-derived VEGF in podocyte defense and survival after PAN injury using conditional transgenic podocytes and mice, in which human VEGF-A (hVEGF) transgene expression is controlled by tetracycline responsive element (TRE) promoter and reverse tetracycline transactivator (rtTA) in podocytes. In vitro experiments used primary cultured podocytes harvested from mice carrying podocin-rtTA and TRE-hVEGF transgenes, in which hVEGF can be induced selectively. Induction of VEGF in PAN-exposed podocytes resulted in preservation of intrinsic VEGF, α-actinin-4 and synaptopodin, antiapoptotic marker Bcl-xL/Bax, as well as attenuation in apoptotic marker cleaved/total caspase-3. In vivo, compared with genotype controls, PAN-sensitive neonatal mice with physiologically relevant levels of podocyte-derived VEGF showed significantly larger glomeruli. Furthermore, PAN-induced up-regulation of desmin, down-regulation of synaptopodin and nephrin, and disruption of glomerular morphology were significantly attenuated in VEGF-induced transgenic mice. Our data indicate that podocyte-derived VEGF provides self-preservation functions, which can rescue the cell after injury and preempt subsequent deterioration of the glomerulus in developing mice.

Induction of sister chromatid exchanges and cell division delays in human lymphocytes by the anti-tumour agent homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenoxy acetic acid.

PubMed

Tselepi, M R; Demopoulos, N A; Catsoulacos, P

1989-09-01

3 beta-Hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam-p-bis(2-chloroethyl) aminophenoxyacetate (NSC 294859) is a new modified steroidal alkylating agent. This compound was given by i.p. administration to mice bearing different types of tumour. It was found to exhibit good activity in L1210 and P388 leukaemias with maintenance of activity against advanced tumours. The treatment of colon 26 tumour and B16 melanoma resulted in positive antineoplastic activity. The drug was not shown to be active in a melphalan-resistant P388 line. In this study, NSC 294859 was found to be effective in causing statistically significant increases in sister-chromatid exchange (SCE) rates and cell division delays. The alkylating agent component, p-bis-(2-chloroethyl)aminophenoxy acetic acid, was shown to be less effective than the parent compound, while the modified steroid component, 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam, showed no effect. There were no statistically significant differences among donors regarding the induction of SCEs and replication indices (RIs) for the compounds tested.

Combinatorial Treatment of DNA and Chromatin-Modifying Drugs Cause Cell Death in Human and Canine Osteosarcoma Cell Lines

PubMed Central

Thayanithy, Venugopal; Park, ChangWon; Sarver, Aaron L.; Kartha, Reena V.; Korpela, Derek M.; Graef, Ashley J.; Steer, Clifford J.; Modiano, Jaime F.; Subramanian, Subbaya

2012-01-01

Downregulation of microRNAs (miRNAs) at the 14q32 locus stabilizes the expression of cMYC, thus significantly contributing to osteosarcoma (OS) pathobiology. Here, we show that downregulation of 14q32 miRNAs is epigenetically regulated. The predicted promoter regions of miRNA clusters at 14q32 locus showed no recurrent patterns of differential methylation, but Saos2 cells showed elevated histone deacetylase (HDAC) activity. Treatment with 4-phenylbutyrate increased acetylation of histones associated with 14q32 miRNAs, but interestingly, robust restoration of 14q32 miRNA expression, attenuation of cMYC expression, and induction of apoptosis required concomitant treatment with 5-Azacytidine, an inhibitor of DNA methylation. These events were associated with genome-wide gene expression changes including induction of pro-apoptotic genes and downregulation of cell cycle genes. Comparable effects were achieved in human and canine OS cells using the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA/Vorinostat) and the DNA methylation inhibitor Zebularine (Zeb), with significantly more pronounced cytotoxicity in cells whose molecular phenotypes were indicative of aggressive biological behavior. These results suggested that the combination of these chromatin-modifying drugs may be a useful adjuvant in the treatment of rapidly progressive OS. PMID:22957032

The preferential accumulation of cadmium in the head portion of the freshwater planarian, Dugesia japonica (Platyhelminthes: Turbellaria).

PubMed

Wu, Jui-Pin; Chen, Hon-Cheng; Li, Mei-Hui

2011-12-01

Free-living freshwater planarians are considered to have the potential for development as an experimental model for toxicological studies on xenobiotics, including metals. However, little was known about the distribution patterns of metals in the body of treated planarians. This study was conducted to determine the tissue distribution patterns of cadmium (Cd) in different body portions of the treated planarian, Dugesia japonica. Results showed that Cd accumulated in the head of planarians at a significantly higher concentration than in the tail. After examining the level of metallothionein (MT), we suggested that the tissue distribution pattern of Cd might be related to MT induction patterns. In contrast, in planarians treated with copper (Cu), neither the tissue accumulation of Cu nor the multiples of induction of MTs significantly differed between different portions. Furthermore, a higher Cd accumulation rate in the head of planarians caused more-severe oxidative stress to appear in this portion and also a higher susceptibility to a lethal concentration of Cd. Finally, both in vitro and in vivo acetylcholinesterase activities in both body portions of planarians were inhibited by Cd. The present study provides the first report that different metals are distributed in various body portions with different patterns in the planarian.

Endosulfan induces CYP2B6 and CYP3A4 by activating the pregnane X receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casabar, Richard C.T.; Das, Parikshit C.; DeKrey, Gregory K.

Endosulfan is an organochlorine pesticide commonly used in agriculture. Endosulfan has affects on vertebrate xenobiotic metabolism pathways that may be mediated, in part, by its ability to activate the pregnane X receptor (PXR) and/or the constitutive androstane receptor (CAR) which can elevate expression of cytochrome P450 (CYP) enzymes. This study examined the dose-dependency and receptor specificity of CYP induction in vitro and in vivo. The HepG2 cell line was transiently transfected with CYP2B6- and CYP3A4-luciferase promoter reporter plasmids along with human PXR (hPXR) or hCAR expression vectors. In the presence of hPXR, endosulfan-alpha exposure caused significant induction of CYP2B6 (16-fold)more » and CYP3A4 (11-fold) promoter activities over control at 10 {mu}M. The metabolite endosulfan sulfate also induced CYP2B6 (12-fold) and CYP3A4 (6-fold) promoter activities over control at 10 {mu}M. In the presence of hCAR-3, endosulfan-alpha induced CYP2B6 (2-fold) promoter activity at 10 {mu}M, but not at lower concentrations. These data indicate that endosulfan-alpha significantly activates hPXR strongly and hCAR weakly. Using western blot analysis of human hepatocytes, the lowest concentrations at which CYP2B6 and CYP3A4 protein levels were found to be significantly elevated by endosulfan-alpha were 1.0 {mu}M and 10 {mu}M, respectively. In mPXR-null/hPXR-transgenic mice, endosulfan-alpha exposure (2.5 mg/kg/day) caused a significant reduction of tribromoethanol-induced sleep times by approximately 50%, whereas no significant change in sleep times was observed in PXR-null mice. These data support the role of endosulfan-alpha as a strong activator of PXR and inducer of CYP2B6 and CYP3A4, which may impact metabolism of CYP2B6 or CYP3A4 substrates.« less

Endosulfan induces CYP2B6 and CYP3A4 by activating the pregnane X receptor.

PubMed

Casabar, Richard C T; Das, Parikshit C; Dekrey, Gregory K; Gardiner, Catherine S; Cao, Yan; Rose, Randy L; Wallace, Andrew D

2010-06-15

Endosulfan is an organochlorine pesticide commonly used in agriculture. Endosulfan has affects on vertebrate xenobiotic metabolism pathways that may be mediated, in part, by its ability to activate the pregnane X receptor (PXR) and/or the constitutive androstane receptor (CAR) which can elevate expression of cytochrome P450 (CYP) enzymes. This study examined the dose-dependency and receptor specificity of CYP induction in vitro and in vivo. The HepG2 cell line was transiently transfected with CYP2B6- and CYP3A4-luciferase promoter reporter plasmids along with human PXR (hPXR) or hCAR expression vectors. In the presence of hPXR, endosulfan-alpha exposure caused significant induction of CYP2B6 (16-fold) and CYP3A4 (11-fold) promoter activities over control at 10 microM. The metabolite endosulfan sulfate also induced CYP2B6 (12-fold) and CYP3A4 (6-fold) promoter activities over control at 10 microM. In the presence of hCAR-3, endosulfan-alpha induced CYP2B6 (2-fold) promoter activity at 10 microM, but not at lower concentrations. These data indicate that endosulfan-alpha significantly activates hPXR strongly and hCAR weakly. Using western blot analysis of human hepatocytes, the lowest concentrations at which CYP2B6 and CYP3A4 protein levels were found to be significantly elevated by endosulfan-alpha were 1.0 microM and 10 microM, respectively. In mPXR-null/hPXR-transgenic mice, endosulfan-alpha exposure (2.5mg/kg/day) caused a significant reduction of tribromoethanol-induced sleep times by approximately 50%, whereas no significant change in sleep times was observed in PXR-null mice. These data support the role of endosulfan-alpha as a strong activator of PXR and inducer of CYP2B6 and CYP3A4, which may impact metabolism of CYP2B6 or CYP3A4 substrates. Copyright 2010 Elsevier Inc. All rights reserved.

Hypnotic induction in dentistry--coping with the fear of losing control (autonomy): a brief communication.

PubMed

Kleinhauz, M; Eli, I

1991-07-01

A common cause of stress among dental patients is the patient's fear of losing control in face of the "helplessness provoking" dental situation. Although hypno-relaxation and hypnosis serve as efficient tools to aid in the administration of dental treatment to such patients, some of them may view hypnosis as a further relinquishing of control to the hypnotist and thus resist hypnotic induction, despite their willingness to try to use hypnosis for therapeutic reasons. To avoid this resistance, a "self-control" induction method is suggested that enables the patient to remain in control throughout the process. This technique minimizes the threat of losing one's autonomy and thus enables treatment of these patients.

Two models for identification and predicting behaviour of an induction motor system

NASA Astrophysics Data System (ADS)

Kuo, Chien-Hsun

2018-01-01

System identification or modelling is the process of building mathematical models of dynamical systems based on the available input and output data from the systems. This paper introduces system identification by using ARX (Auto Regressive with eXogeneous input) and ARMAX (Auto Regressive Moving Average with eXogeneous input) models. Through the identified system model, the predicted output could be compared with the measured one to help prevent the motor faults from developing into a catastrophic machine failure and avoid unnecessary costs and delays caused by the need to carry out unscheduled repairs. The induction motor system is illustrated as an example. Numerical and experimental results are shown for the identified induction motor system.

A randomized trial of misoprostol versus extra-amniotic sodium chloride infusion with oxytocin for induction of labor.

PubMed

Buccellato, C A; Stika, C S; Frederiksen, M C

2000-05-01

Our purpose was to compare the efficacy and safety of misoprostol and extra-amniotic sodium chloride infusion with oxytocin for induction of labor. This randomized trial compared two methods of labor induction in women requiring cervical ripening. One hundred twenty-three women undergoing labor induction with a Bishop score < or =5 were randomly selected to receive either misoprostol, 50 microg intravaginally every 4 hours, or extra-amniotic sodium chloride infusion. The primary outcome variable was the time interval from induction to vaginal delivery. Sixty-one women received extra-amniotic sodium chloride infusion and 62 women received misoprostol. The mean time interval from the start of induction to vaginal delivery was 15.0 +/- 5.0 hours and 16.5 +/- 7.2 hours for the extra-amniotic infusion and misoprostol groups, respectively (P, not significant). The cesarean delivery rate was not significantly different between the 2 groups (32.8% for the extra-amniotic infusion group; 19.4% for the misoprostol group). Maternal and neonatal outcomes were similar between the 2 groups. Both methods of induction are equally efficacious and result in similar maternal and neonatal outcomes.

Functional changes in cerebral 5-hydroxytryptamine metabolism in the mouse induced by anticonvulsant drugs.

PubMed Central

Chadwick, D; Gorrod, J W; Jenner, P; Marsden, C D; Reynolds, E H

1978-01-01

1 Acute administration of clonazepam, diazepam, and diphenylhydantoin to mice elevated cerebral 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA); chronic administration had less effect. 2 Acute administration of clonazepam and diazepam but not diphenylhydantoin raised cerebral trytophan levels; chronic administration of clonazepam caused a smaller elevation of cerebral tryptophan but chronic administration of diazepam still caused a large rise in cerebral tryptophan. 3 Neither clonazepam nor diazepam caused induction of drug metabolizing enzymes on chronic administration but diphenylhydantoin had a marked effect. 4 These data suggest that the altered 5-HT metabolism caused by these compounds is unrelated to a common action on tryptophan levels, and that the reduced effect of clonazepam and diazepam on chronic administration cannot be attributed to increased metabolism of these compounds. 5 Clonazepam induced abnormal head movements in mice in a dose-dependent manner. Pretreatment of animals with tranylcypromine increased the intensity of movement, although pargyline was without effect. Similar effects were observed with diazepam and diphenylhydantoin, suggesting that the increase in cerebral 5-HT caused by these compounds is of functional significance in stimulating 5-HT receptors. PMID:620092

Reduced calcium/calmodulin-dependent protein kinase II activity in the hippocampus is associated with impaired cognitive function in MPTP-treated mice.

PubMed

Moriguchi, Shigeki; Yabuki, Yasushi; Fukunaga, Kohji

2012-02-01

Parkinson's disease (PD) patients frequently reveal deficit in cognitive functions during the early stage in PD. The dopaminergic neurotoxin, MPTP-induced neurodegeneration causes an injury of the basal ganglia and is associated with PD-like behaviors. In this study, we demonstrated that deficits in cognitive functions in MPTP-treated mice were associated with reduced calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation and impaired long-term potentiation (LTP) induction in the hippocampal CA1 region. Mice were injected once a day for 5days with MPTP (25mg/kg i.p.). The impaired motor coordination was observed 1 or 2week after MPTP treatment as assessed by rota-rod and beam-walking tasks. In immunoblotting analyses, the levels of tyrosine hydroxylase protein and CaMKII autophosphorylation in the striatum were significantly decreased 1week after MPTP treatment. By contrast, deficits of cognitive functions were observed 3-4weeks after MPTP treatment as assessed by novel object recognition and passive avoidance tasks but not Y-maze task. Impaired LTP in the hippocampal CA1 region was also observed in MPTP-treated mice. Concomitant with impaired LTP induction, CaMKII autophosphorylation was significantly decreased 3weeks after MPTP treatment in the hippocampal CA1 region. Finally, the reduced CaMKII autophosphorylation was closely associated with reduced AMPA-type glutamate receptor subunit 1 (GluR1; Ser-831) phosphorylation in the hippocampal CA1 region of MPTP-treated mice. Taken together, decreased CaMKII activity with concomitant impaired LTP induction in the hippocampus likely account for the learning disability observed in MPTP-treated mice. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Poincaré plot indexes of heart rate variability detect dynamic autonomic modulation during general anesthesia induction.

PubMed

Hsu, Che-Hao; Tsai, Ming-Ya; Huang, Go-Shine; Lin, Tso-Chou; Chen, Kuen-Pao; Ho, Shung-Tai; Shyu, Liang-Yu; Li, Chi-Yuan

2012-03-01

Beat-to-beat heart rate variability (HRV) is caused by the fluctuating balance of sympathetic and parasympathetic tone. The Poincaré plot has been used to evaluate HRV. In this study, we validate that this new method may qualitatively and quantitatively assess the sympathovagal fluctuation in patients during induction of anesthesia with sevoflurane. Twenty-eight young patients were allocated for the study. The patients received a tilt test and on the next day they sustained anesthesia induced with inhaled anesthetics. Electrocardiography signals from the patients were relayed to an analogue-digital converter. The Poincaré plot is quantified by measuring SD1, SD2, and SD1/SD2. Power spectral analyses were performed and LF, HF and HF/LF were calculated. The LF power and the SD2 of the Poincaré plot increased while subjects were tilt-up from the supine position. Additionally, a significant correlation were found between LF and SD2, HF and SD1 (p < 0.05), and LF/HF and SD2/SD1 (p < 0.01). Sevoflurane inhalation for 10 minutes had no effect on heart rate, but diminished LF, total power and SD1, SD2 of the Poincaré plot respectively. However, the LF, SD2 and LF/HF increased; the HF, SD1 and SD1/SD2 ratio decreased after intubation stimulation. Poincaré plot and power spectral analysis of HRV during tilt test and sevoflurane induction significantly correlate. Poincaré plot analysis is easier and more sensitive at evaluating the sympathovagal balance and observing the beat-to-beat HRV. Copyright © 2012. Published by Elsevier B.V.

Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge

Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performedmore » 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.« less

Endoplasmic reticulum stress is important for the manifestations of α-synucleinopathy in vivo

PubMed Central

Colla, Emanuela; Coune, Philippe; Liu, Ying; Pletnikova, Olga; Troncoso, Juan C; Iwatsubo, Takeshi; Schneider, Bernard L.; Lee, Michael K.

2012-01-01

Accumulation of misfolded α-synuclein (αS) is mechanistically linked to neurodegeneration in Parkinson's disease (PD) and other α-synucleinopathies. However, how αS causes neurodegeneration is unresolved. Because cellular accumulation of misfolded proteins can lead to endoplasmic reticulum stress/unfolded protein response (ERS/UPR), chronic ERS could contribute to neurodegeneration in α-synucleinopathy. Using the A53T mutant human αS transgenic (A53TαS Tg) mouse model of α-synucleinopathy, we show that disease onset in the αS Tg model is coincident with induction of ER chaperone in neurons exhibiting αS pathology. However, the neuronal ER chaperone induction was not accompanied by the activation of phospho-eIF2α, indicating that α-synucleinopathy is associated with abnormal UPR that could promote cell death. Induction of ERS/UPR was associated with increased levels of ER/microsomal (ER/M) associated αS monomers and aggregates. Significantly, human PD cases also exhibit higher relative levels of ER/M αS than the control cases. Moreover, αS interacts with ER chaperones and overexpression of αS sensitizes neuronal cells to ERS-induced toxicity, suggesting that αS may have direct impact on ER function. This view is supported by the presence of ERS-activated caspase-12 and the accumulation of ER-associated polyubiquitin. More important, treatment with Salubrinal, an anti-ERS compound, significantly attenuates disease manifestations in both the A53TαS Tg mouse model and the Adeno-associated Virus-transduced rat model of A53T α S-dependent dopaminergic neurodegeneration. Our data indicate that the accumulation αS within ER leads to chronic ER stress conditions that contribute to neurodegeneration in α-synucleinopathies. Attenuating chronic ERS could be an effective therapy for PD and other α-synucleinopathies. PMID:22399753

Early immune response and regulation of IL-2 receptor subunits

NASA Technical Reports Server (NTRS)

Hughes-Fulford, Millie; Sugano, Eiko; Schopper, Thomas; Li, Chai-Fei; Boonyaratanakornkit, J. B.; Cogoli, Augusto

2005-01-01

Affymetrix oligonucleotide arrays were used to monitor expression of 8796 genes and probe sets in activated T-cells; analysis revealed that 217 genes were significantly upregulated within 4 h. Induced genes included transcription factors, cytokines and their receptor genes. Analysis by semi-quantitative RT-PCR confirmed the significant induction of IL-2, IL-2R(gamma) and IL-2R(alpha). Forty-eight of the 217 induced genes are known to or predicted to be regulated by a CRE promoter/enhancer. We found that T-cell activation caused a significant increase in CREB phosphorylation furthermore, inhibition of the PKC pathway by GF109203 reduced CREB activation by 50% and inhibition of the PKA pathway caused a total block of CREB phosphorylation and significantly reduced IFN(gamma), IL-2 and IL-2R(alpha) gene expression by approximately 40% (p<0.001). PKC(theta) plays a major role in T-cell activation: inhibition of PKC significantly reduced the expression of IFN(gamma), IL-2 and IL-2R(alpha). Since PKC blocked activation of CREB, we studied potential cross-talk between the PKC and the PKA/MAPK pathways, PMA-stimulated Jurkat cells were studied with specific signal pathway inhibitors. Extracellular signal-regulated kinase-2 (ERK2) pathway was found to be significantly activated greater than seven-fold within 30 min; however, there was little activation of ERK-1 and no activation of JNK or p38 MAPK. Inhibition of the PKA pathway, but not the PKC pathway, resulted in inhibition of ERK1/2 activation at all time points, inhibition of MEK1 and 2 significantly blocked expression of IL-2 and IL-2R(alpha). Gene expression of IL-2R(alpha) and IFN(gamma) was dependent on PKA in S49 wt cells but not in kin- mutants. Using gel shift analysis, we found that forskolin activation of T-cells resulted in activation of AP1 sites; this increase in nuclear extract AP1 was significantly blocked by MEK1 inhibitor U0126. Taken together, these results suggest that the PKA in addition to PKC and MAPK pathways plays a role in early T-cell activation and induction of IL-2, IL-2R(alpha) and IFN(gamma) gene expression.

Early immune response and regulation of IL-2 receptor subunits.

PubMed

Hughes-Fulford, Millie; Sugano, Eiko; Schopper, Thomas; Li, Chai-Fei; Boonyaratanakornkit, J B; Cogoli, Augusto

2005-09-01

Affymetrix oligonucleotide arrays were used to monitor expression of 8796 genes and probe sets in activated T-cells; analysis revealed that 217 genes were significantly upregulated within 4 h. Induced genes included transcription factors, cytokines and their receptor genes. Analysis by semi-quantitative RT-PCR confirmed the significant induction of IL-2, IL-2R(gamma) and IL-2R(alpha). Forty-eight of the 217 induced genes are known to or predicted to be regulated by a CRE promoter/enhancer. We found that T-cell activation caused a significant increase in CREB phosphorylation furthermore, inhibition of the PKC pathway by GF109203 reduced CREB activation by 50% and inhibition of the PKA pathway caused a total block of CREB phosphorylation and significantly reduced IFN(gamma), IL-2 and IL-2R(alpha) gene expression by approximately 40% (p<0.001). PKC(theta) plays a major role in T-cell activation: inhibition of PKC significantly reduced the expression of IFN(gamma), IL-2 and IL-2R(alpha). Since PKC blocked activation of CREB, we studied potential cross-talk between the PKC and the PKA/MAPK pathways, PMA-stimulated Jurkat cells were studied with specific signal pathway inhibitors. Extracellular signal-regulated kinase-2 (ERK2) pathway was found to be significantly activated greater than seven-fold within 30 min; however, there was little activation of ERK-1 and no activation of JNK or p38 MAPK. Inhibition of the PKA pathway, but not the PKC pathway, resulted in inhibition of ERK1/2 activation at all time points, inhibition of MEK1 and 2 significantly blocked expression of IL-2 and IL-2R(alpha). Gene expression of IL-2R(alpha) and IFN(gamma) was dependent on PKA in S49 wt cells but not in kin- mutants. Using gel shift analysis, we found that forskolin activation of T-cells resulted in activation of AP1 sites; this increase in nuclear extract AP1 was significantly blocked by MEK1 inhibitor U0126. Taken together, these results suggest that the PKA in addition to PKC and MAPK pathways plays a role in early T-cell activation and induction of IL-2, IL-2R(alpha) and IFN(gamma) gene expression.

Parental presence during induction of anesthesia: physiological effects on parents.

PubMed

Kain, Zeev N; Caldwell-Andrews, Alison A; Mayes, Linda C; Wang, Shu-Ming; Krivutza, Dawn M; LoDolce, Megan E

2003-01-01

The authors conducted a randomized controlled trial to determine whether parental presence during induction of anesthesia (PPIA) is associated with parental physiologic and behavioral manifestations of stress. Children and their parents (N = 80) were randomly assigned to one of three groups: (1) PPIA; (2) PPIA plus 0.5 mg/kg oral midazolam; and (3) control (no PPIA or midazolam). The effect of the group assignment on parental heart rate (HR), parental blood pressure, and parental skin conductance level (SCL) were assessed. Both parental HR and parental SCL were monitored continually. Anxiety of the parent and child was also assessed. Parental HR increased from baseline until the induction of anesthesia (P = 0.001). A group-by-time effect ( P= 0.005) was also found. That is, throughout the induction period there were several time points at which parents in the two PPIA groups had a significantly higher HR than did parents in the control group (P < 0.05). Similarly, SCL was found to increase in all parents from baseline until induction of anesthesia (P = 0.001). Significant group differences in SCL changes over time were found as well (P = 0.009). State anxiety and blood pressure following induction of anesthesia did not differ significantly between groups ( P= nonsignificant). Examination of parental Holter data revealed no rhythm abnormalities and no electrocardiogram changes indicating ischemia. The authors found that PPIA is associated with increased parental HR and SCL. However, no increased incidence of electrocardiogram abnormalities were found in parents present during induction of anesthesia.

Source-Related Effects of Wastewater on Transcription Factor (AhR, CAR and PXR)-Mediated Induction of Gene Expression in Cultured Rat Hepatocytes and Their Association with the Prevalence of Antimicrobial-Resistant Escherichia coli

PubMed Central

Guruge, Keerthi S.; Yamanaka, Noriko; Sonobe, Miyuki; Fujizono, Wataru; Yoshioka, Miyako; Akiba, Masato; Yamamoto, Takehisa; Joshua, Derrick I.; Balakrishna, Keshava; Yamashita, Nobuyoshi; Kannan, Kurunthachalam; Tsutsui, Toshiyuki

2015-01-01

Extracts of wastewater collected from 4 sewage treatment plants (STPs) receiving effluents from different sources in South India were investigated for their levels of transcription factor-mediated gene induction in primary cultured rat hepatocytes. In addition, the relation between gene induction levels and the prevalence of antimicrobial-resistant Escherichia coli (E. coli) in wastewater was examined. STP-3, which treats only hospital wastewater, exhibited significantly greater induction potency of all 6 drug metabolizing cytochrome P450 (CYP) genes examined, CYP1A1, 1A2, 1B1, 2B15, 3A1, and 3A2, whereas the wastewater at STP-1, which exclusively receives domestic sewage, showed significantly diminished levels of induction of 3 CYP genes when compared to the levels of CYP induction at STP-2, which receives mixed wastewater. Samples collected during the monsoon season showed a significantly altered gene induction capacity compared to that of samples from the pre-monsoon period. The data suggest that the toxicity of wastewater in STPs was not significantly diminished during the treatment process. The chemical-gene interaction data predicted that a vast number of chemicals present in the wastewater would stimulate the genes studied in the rat hepatocytes. The multivariable logistic regression analysis demonstrated that the prevalence of isolates resistant to cefotaxime, imipenem and streptomycin was significantly correlated with the levels of induction of at least three CYP-isozymes in STP wastewater. In addition, the resistance of isolates in treatment plants was not altered by the treatment steps, whereas the sampling season did have an impact on the resistance to specific antimicrobials. The identification of receptor-mediated gene regulation capacities offers important data not limited to the (synergistic) physiological role of chemicals in biological systems but may provide new insight into the link between the effects of known/unknown drugs and prevalence of antimicrobial-resistant bacteria in wastewater. PMID:26381891

Gravitational induction

NASA Astrophysics Data System (ADS)

Bini, Donato; Cherubini, Christian; Chicone, Carmen; Mashhoon, Bahram

2008-11-01

We study the linear post-Newtonian approximation to general relativity known as gravitoelectromagnetism (GEM); in particular, we examine the similarities and differences between GEM and electrodynamics. Notwithstanding some significant differences between them, we find that a special nonstationary metric in GEM can be employed to show explicitly that it is possible to introduce gravitational induction within GEM in close analogy with Faraday's law of induction and Lenz's law in electrodynamics. Some of the physical implications of gravitational induction are briefly discussed.

Comparison of blood pressure and thermal responses in rats exposed to millimeter wave energy or environmental heat.

PubMed

Millenbaugh, Nancy J; Kiel, Johnathan L; Ryan, Kathy L; Blystone, Robert V; Kalns, John E; Brott, Becky J; Cerna, Cesario Z; Lawrence, William S; Soza, Laura L; Mason, Patrick A

2006-06-01

Electromagnetic fields at millimeter wave lengths are being developed for commercial and military use at power levels that can cause temperature increases in the skin. Previous work suggests that sustained exposure to millimeter waves causes greater heating of skin, leading to faster induction of circulatory failure than exposure to environmental heat (EH). We tested this hypothesis in three separate experiments by comparing temperature changes in skin, subcutis, and colon, and the time to reach circulatory collapse (mean arterial blood pressure, 20 mmHg) in male Sprague-Dawley rats exposed to the following conditions that produced similar rates of body core heating within each experiment: (1) EH at 42 degrees C, 35 GHz at 75 mW/cm, or 94 GHz at 75 mW/cm under ketamine and xylazine anesthesia; (2) EH at 43 degrees C, 35 GHz at 90 mW/cm, or 94 GHz at 90 mW/cm under ketamine and xylazine anesthesia; and (3) EH at 42 degrees C, 35 GHz at 90 mW/cm, or 94 GHz at 75 mW/cm under isoflurane anesthesia. In all three experiments, the rate and amount of temperature increase at the subcutis and skin surface differed significantly in the rank order of 94 GHz more than 35 GHz more than EH. The time to reach circulatory collapse was significantly less only for rats exposed to 94 GHz at 90 mW/cm, the group with the greatest rate of skin and subcutis heating of all groups in this study, compared with both the 35 GHz at 90 mW/cm and the EH at 43 degrees C groups. These data indicate that body core heating is the major determinant of induction of hemodynamic collapse, and the influence of heating of the skin and subcutis becomes significant only when a certain threshold rate of heating of these tissues is exceeded.

Periodic acid‑Schiff staining method for function detection of liver cells is affected by 2% horse serum in induction medium.

PubMed

Hui, Hui; Ma, Wenjun; Cui, Jiejie; Gong, Mengjia; Wang, Yi; Zhang, Yuanyuan; He, Tongchuan; Bi, Yang; He, Yun

2017-12-01

Developing a thorough understanding of experimental methods of hepatic differentiation in hepatic progenitor cells (HPCs) should expand the knowledge of hepatocyte induction in vitro and may help to develop cell transplantation therapies for the clinical usage of HPCs in liver diseases. A previous induction method effectively induced differentiation and metabolic abilities in HPCs. Periodic acid‑Schiff (PAS) staining is used to identify glycogen synthesis and hepatocyte function; however, this method failed to detect induced hepatocytes. The present study aimed to investigate the possible factors affecting the previous confusing results of PAS staining. Removal of single induction factors, including dexamethasone, hepatic growth factor and fibroblast growth factor 4 from the induction media did not restore PAS staining, whereas replacement of 2% horse serum (HS) with 10% fetal bovine serum (FBS) significantly increased the number of PAS positive cells. Following 12 days of basal induction, replacing the induction medium with media containing 10% FBS for 12‑72 h significantly improved PAS staining, but did not influence indocyanine green uptake. Furthermore, incubation in induction medium with 10% FBS following 12 days of normal induction did not affect the expression of hepatic markers and mature function of HPCs. Therefore, the present study suggested that 2% HS in the induction medium did not affect the hepatic function of induced cells, but did affect glycogen storage, whereas replacement of medium with 10% FBS in advance of PAS staining may restore the failure of PAS staining in low serum concentrations of induced hepatocytes.

Outcome of children with acute myeloid leukaemia (AML) experiencing primary induction failure in the AIEOP AML 2002/01 clinical trial.

PubMed

Quarello, Paola; Fagioli, Franca; Basso, Giuseppe; Putti, Maria C; Berger, Massimo; Luciani, Matteo; Rizzari, Carmelo; Menna, Giuseppe; Masetti, Riccardo; Locatelli, Franco

2015-11-01

Paediatric patients with acute myeloid leukaemia (AML) who fail induction due to primary resistance to chemotherapy account for a significant proportion of cases and have a particularly dismal prognosis. We report the clinical and biological data, and final outcome of 48 paediatric patients with primary-resistant AML enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 clinical trial. These patients had a significantly higher white blood cell count at diagnosis compared to other AML patients. Cytogenetic and molecular features did not differ between patients with primary induction failure and patients allocated to the high-risk group. For the whole patient population, the probability of overall survival, event-free survival (EFS) and disease-free survival (DFS) was 21·8% ± 6·2, 20·4% ± 5·9, and 49·5% ± 11·3, respectively. Twenty-eight (58%) patients received haematopoietic stem cell transplantation (HSCT); 3 were autologous and 25 were allogeneic. Patients who underwent HSCT had improved EFS (31·2% vs. 5%, P < 0·0001). Only one of the 20 patients who did not receive HSCT is alive and disease free. The 19 patients in complete remission at time of HSCT showed significantly better DFS than the 9 with active disease (46% vs. 0%, P = 0·02). This study represents one of the largest series with long-term follow up of paediatric AML patients with primary refractory disease. Children who underwent transplantation had an encouraging long-term outcome. Disease recurrence remains the major cause of treatment failure; a better understanding of the disease biology is desirable to develop more effective treatment strategies. © 2015 John Wiley & Sons Ltd.

N-acetylcysteine amid reduces pancreatic damage in a rat model of acute necrotizing pancreatitis.

PubMed

Turkyilmaz, Serdar; Usta, Arif; Cekic, Arif Burak; Alhan, Etem; Kural, Birgül Vanizor; Ercin, Cengiz

2016-06-15

Inflammatory explosion and oxidative stress are important mechanisms of injury in acute necrotizing pancreatitis (ANP). This study investigated the effects of N-acetylcysteine amid (NACA), a novel cell-permeant antioxidant with anti-inflammatory activity, on experimental ANP in rats. Fifty-two adult male Sprague-Dawley rats were used, and ANP was induced by cerulein. The animals were divided into four groups which were sham + saline, sham + NACA, ANP + saline, and ANP + NACA. NACA (2.2 mg/kg, i.p) was administered for 6 h, after the induction of ANP. The extent of acinar cell injury, mortality, systemic cardiorespiratory variables, functional capillary density, renal/hepatic functions, and changes in some enzyme markers for pancreas and lung tissues were investigated. Induction of ANP increased mortality from 0% in the sham group to 43.75% in the ANP + saline group (P < 0.05), and administration of NACA significantly reduced mortality to 12.5% (P < 0.05). Induction of ANP also caused increases in pancreatic necrosis, serum amylase, alanine aminotransferase (ALT), interleukin-6, LDH in bronchoalveolar lavage fluid, serum urea, tissue myeloperoxidase in pancreas and lung tissues and malondialdehyde. There was less pronounced increase in these parameters in NACA treated group. Compared with ANP group, ANP + NACA group had lower levels of pancreatic necrosis (0.5 ± 0.2 versus 1.45 ± 0.2, P < 0.05) and inflammation (0.6 ± 0.2 versus 1.29 ± 00.3, P < 0.05) scores. Administration of NACA significantly decreased the ANP-induced mortality and also provided significant improvements in hemodynamic changes. The obtained positive effects of NACA on the course of pancreatitis indicates its potential usefulness in the management of ANP. Copyright © 2016 Elsevier Inc. All rights reserved.

Induction of Protective Immunity against Eimeria tenella Infection using Antigen-loaded Dendritic Cells (DC) and DC-derived Exosomes

USDA-ARS?s Scientific Manuscript database

Eimeria is a protozoan parasite which causes coccidiosis, a major parasitic disease of poultry that is indigenous to most regions of the world and causes intestinal damage with reduced body weight gain. Conventional disease control methods have relied on prophylactic chemotherapy, but alternative m...

THE ROLE OF GENETIC SUSCEPTIBILITY IN EXPERIMENTAL INDUCTION CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND PARTICULATE MATTER (PM) HEALTH EFFECTS.

EPA Science Inventory

Human COPD represents the 4th common cause of mortality worldwide and is characterized by presence of chronic bronchitis/inflammation and emphysema. The primary cause is cigarette smoking, as nearly all COPD patients are smokers. However, only about 10% of smokers develop this di...

Comparative study of titrated oral misoprostol solution and vaginal dinoprostone for labor induction at term pregnancy.

PubMed

Wang, Xiu; Yang, Aijun; Ma, Qingyong; Li, Xuelan; Qin, Li; He, Tongqiang

2016-09-01

To evaluate effectiveness and safety of titrated oral misoprostol solution (OMS) in comparison with vaginal dinoprostone for cervix ripening and labor induction in term pregnant women. A multicenter randomized controlled trial of women with term singleton pregnancy with indications for labor induction; 481 participants were allocated to receive titrated OMS with different doses by hourly administration according to the procedure or insert vaginal dinoprostone for cervix ripening and labor induction to compare maternal outcomes including indication of labor induction, mode of outcome of delivery, maternal morbidity, and neonatal outcomes between two groups for evaluating the efficacy and safety of titrated oral misoprostol induction. Proportion of delivery within 12 h of titrated oral misoprostol is significantly less than vaginal dinoprostone (p = 0.03), but no difference of total vaginal delivery rate (p = 0.93); the mean time of first treatment to vaginal delivery was longer in OMS group (21.3 ± 14.5 h) compared with the vaginal dinoprostone group (15.7 ± 9.6 h). Although the proportion of cesarean section between the two groups showed no statistically significant difference, OMS group showed significantly lower frequency of uterine hyperstimulation, hypertonus, partus precipitatus and non-reassuring fetal heart rate than dinoprostone group. Neonatal outcomes were similar evaluating from Apgar score and NICU admission. Our study also showed that labor induction of women with cervix Bishop score ≤3 needed increased dosage of misoprostol solution. Titrated OMS is as effective as vaginal dinoprostone in labor induction for term pregnant women, with safer effect for its lower rate of adverse effect for women.

Sustained neuroprotection from a single intravitreal injection of PGJ2 in a rodent model of anterior ischemic optic neuropathy.

PubMed

Touitou, Valerie; Johnson, Mary A; Guo, Yan; Miller, Neil R; Bernstein, Steven L

2013-11-11

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of sudden optic nerve-related vision loss in persons older than 50 in the United States. There currently is no treatment for this disorder. We previously showed that systemic administration of 15-deoxy, delta (12, 14) prostaglandin J2 (PGJ2) is neuroprotective in our rodent model of AION (rAION). In this study, we determined if a single intravitreal (IVT) injection of PGJ2 is neuroprotective after rAION, and if this method of administration is toxic to the retina, optic nerve, or both. TOXICITY was assessed after a single IVT injection of PGJ2 in one eye and PBS in the contralateral eye of normal, adult Long-Evans rats. EFFICACY was assessed by inducing rAION in one eye and injecting either PGJ2 or vehicle immediately following induction, with the fellow eye serving as naïve control. Visual evoked potentials (VEPs) and ERGs were performed before induction and at specific intervals thereafter. Animals were euthanized 30 days after induction, after which immunohistochemistry, transmission electron microscopy, and quantitative stereology of retinal ganglion cell (RGC) numbers were performed. IVT PGJ2 did not alter the VEP or ERG compared with PBS-injected control eyes, and neither IVT PGJ2 nor PBS reduced overall RGC numbers. IVT PGJ2 preserved VEP amplitude, reduced optic nerve edema, and resulted in significant preservation of RGCs and axons in eyes with rAION. A single IVT injection of PGJ2 is nontoxic to the retina and optic nerve and neuroprotective when given immediately after rAION induction.

Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells

PubMed Central

Khan, Naghma; Afaq, Farrukh; Syed, Deeba N.; Mukhtar, Hasan

2008-01-01

Novel dietary agents for prevention and therapy of prostate cancer (PCa) are desired. The aim of this study was to determine the effect of fisetin, a tetrahydroxyflavone, on inhibition of cell growth and induction of apoptosis in human PCa cells. Treatment of fisetin (10–60 μM, 48 h) was found to result in a decrease in the viability of LNCaP, CWR22Rυ1 and PC-3 cells but had only minimal effects on normal prostate epithelial cells as assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide assay. Treatment of LNCaP cells with fisetin also resulted in G1-phase arrest that was associated with a marked decrease in the protein expression of cyclins D1, D2 and E and their activating partner cyclin-dependent kinases 2, 4 and 6 with concomitant induction of WAF1/p21 and KIP1/p27. Fisetin treatment also resulted in induction of apoptosis, poly (ADP-ribose) polymerase (PARP) cleavage, modulation in the expressions of Bcl-2 family proteins, inhibition of phosphatidyl inositol 3-kinase and phosphorylation of Akt at Ser473 and Thr308. There was also induction of mitochondrial release of cytochrome c into cytosol, downregulation of X-linked inhibitor of apoptosis protein and upregulation of second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI on treatment of cells with fisetin. Treatment of cells with fisetin also resulted in significant activation of caspases-3, -8 and -9. Pretreatment of cells with caspase inhibitor (Z-VAD-FMK) blocked fisetin-induced activation of caspases. These data provide the first evidence that fisetin could be developed as an agent against PCa. PMID:18359761

Deletion analysis of Streptococcus pneumoniae late competence genes distinguishes virulence determinants that are dependent or independent of competence induction

PubMed Central

Zhu, Luchang; Lin, Jingjun; Kuang, Zhizhou; Vidal, Jorge E.; Lau, Gee W.

2015-01-01

Summary The competence regulon of Streptococcus pneumoniae (pneumococcus) is crucial for genetic transformation. During competence development, the alternative sigma factor ComX is activated, which in turn, initiates transcription of 80 “late” competence genes. Interestingly, only 16 late genes are essential for genetic transformation. We hypothesized that these late genes that are dispensable for competence are beneficial to pneumococcal fitness during infection. These late genes were systematically deleted, and the resulting mutants were examined for their fitness during mouse models of bacteremia and acute pneumonia. Among these, 14 late genes were important for fitness in mice. Significantly, deletion of some late genes attenuated pneumococcal fitness to the same level in both wild-type and ComX-null genetic backgrounds, suggesting that the constitutive baseline expression of these genes was important for bacterial fitness. In contrast, some mutants were attenuated only in the wild-type genetic background but not in the ComX-null background, suggesting that specific expression of these genes during competence state contributed to pneumococcal fitness. Increased virulence during competence state was partially caused by the induction of allolytic enzymes that enhanced pneumolysin release. These results distinguish the role of basal expression versus competence induction in virulence functions encoded by ComX-regulated late competence genes. Graphical abstract During genetic transformation of pneumococcus, the alternative sigma factor ComX regulates expression of 14 late competence genes important for virulence. The constitutive baseline expression of some of these genes is important for bacteremia and acute pneumonia infections. In contrast, elevated expression of DprA, CbpD, CibAB, and Cinbox are dependent on competence development, enhancing the release of pneumolysin. These results distinguish the role of basal expression versus competence induction in virulence determinants regulated by ComX. PMID:25846124

Increased dietary sodium induces COX2 expression by activating NFκB in renal medullary interstitial cells.

PubMed

He, Wenjuan; Zhang, Min; Zhao, Min; Davis, Linda S; Blackwell, Timothy S; Yull, Fiona; Breyer, Matthew D; Hao, Chuan-Ming

2014-02-01

High salt diet induces renal medullary cyclooxygenase 2 (COX2) expression. Selective blockade of renal medullary COX2 activity in rats causes salt-sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NFκB in mediating this COX2 induction in response to increased dietary salt. High salt diet (8 % NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6 J mice. Co-immunofluorescence using a COX2 antibody and antibodies against aquaporin-2, ClC-K, aquaporin-1, and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a sevenfold increase of luciferase activity in the renal medulla of the NFκB-luciferase reporter mice following high salt diet, and a robust induction of enhanced green fluorescent protein (EGFP) expression mainly in renal medullary interstitial cells of the NFκB-EGFP reporter mice following high salt diet. Treating high salt diet-fed C57Bl/6 J mice with selective IκB kinase inhibitor IMD-0354 (8 mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary prostaglandin E2 (PGE2). These data therefore suggest that renal medullary interstitial cell NFκB plays an important role in mediating renal medullary COX2 expression and promoting renal PGE2 synthesis in response to increased dietary sodium.

Cellular Fibronectin Expression in Human Trabecular Meshwork and Induction by Transforming Growth Factor-β2

PubMed Central

Medina-Ortiz, Wanda E.; Belmares, Ricardo; Neubauer, Sandra; Wordinger, Robert J.; Clark, Abbot F.

2013-01-01

Purpose. Levels of TGF-β2 are higher in POAG aqueous humor, causing deposition of extracellular matrix (ECM) proteins, including fibronectin (FN), in the glaucomatous human trabecular meshwork (HTM) that may be responsible for elevated IOP. The purpose of this study was to identify the expression of cellular FN (cFN) isoforms (EDA and EDB) in HTM cells and tissues, and to determine whether TGF-β2 can induce cFN expression and fibril formation in cultured HTM cells. Methods. Expression of cFN mRNA isoforms and induction by recombinant TGF-β2 (5 ng/mL) were determined by quantitative RT-PCR. The TGF-β2 induction of EDA isoform protein expression and FN fibril formation were analyzed using Western immunoblots and immunocytochemistry (ICC), respectively. Immunohistochemistry (IHC) analysis was used to examine total FN and EDA isoform expression in normal (NTM) and glaucomatous (GTM) trabecular meshwork (TM) tissues. Results. Both cFN mRNA isoforms were expressed in cultured HTM cells and were induced by TGF-β2 after 2, 4, and 7 days (P < 0.05). Similarly, EDA isoform protein and fibril formation were increased after 4 and 7 days of TGF-β2 treatment. Finally, GTM tissues had significantly greater EDA isoform protein levels (1.7-fold, P < 0.05) compared to NTM tissues. Conclusions. This study demonstrated that cFN isoforms are expressed and induced in HTM cells by TGF-β2. Also, increased EDA isoform protein levels were seen in GTM tissues. Our findings suggest that induction of cFN isoform expression in the TM ECM may be a novel pathologic mechanism involved in the TM changes associated with glaucoma. PMID:24030464

Neurogenic transdifferentiation of human adipose-derived stem cells? A critical protocol reevaluation with special emphasis on cell proliferation and cell cycle alterations.

PubMed

Kompisch, Kai Michael; Lange, Claudia; Steinemann, Doris; Skawran, Britta; Schlegelberger, Brigitte; Müller, Reinhard; Schumacher, Udo

2010-11-01

Adipose-derived stem cells (ASCs) are reported to display multilineage differentiation potential, including neuroectodermal pathways. The aim of the present study was to critically re-evaluate the potential neurogenic (trans-)differentiation capacity of ASCs using a neurogenic induction protocol based on the combination of isobutylmethylxanthine (IBMX), indomethacin and insulin. ASCs isolated from lipo-aspirate samples of five healthy female donors were characterized and potential neurogenic (trans-)differentiation was assessed by means of immunohistochemistry and gene expression analyses. Cell proliferation and cell cycle alterations were studied, and the expression of CREB/ATF transcription factors was analyzed. ASCs expressed CD59, CD90 and CD105, and were tested negative for CD34 and CD45. Under neurogenic induction, ASCs adopted a characteristic morphology comparable to neur(on)al progenitors and expressed musashi1, β-III-tubulin and nestin. Gene expression analyses revealed an increased expression of β-III-tubulin, GFAP, vimentin and BDNF, as well as SOX4 in induced ASCs. Cell proliferation was significantly reduced under neurogenic induction; cell cycle analyses showed a G2-cell cycle arrest accompanied by differential expression of key regulators of cell cycle progression. Differential expression of CREB/ATF transcription factors could be observed on neurogenic induction, pointing to a decisive role of the cAMP-CREB/ATF system. Our findings may point to a potential neurogenic (trans-)differentiation of ASCs into early neur(on)al progenitors, but do not present definite evidence for it. Especially, the adoption of a neural progenitor cell-like morphology must not automatically be misinterpreted as a specific characteristic of a respective (trans-)differentiation process, as this may as well be caused by alterations of cell cycle progression.

MHC-mismatched mixed chimerism augments thymic regulatory T-cell production and prevents relapse of EAE in mice

PubMed Central

Wu, Limin; Li, Nainong; Zhang, Mingfeng; Xue, Sheng-Li; Cassady, Kaniel; Lin, Qing; Riggs, Arthur D.; Zeng, Defu

2015-01-01

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system with demyelination, axon damage, and paralysis. Induction of mixed chimerism with allogeneic donors has been shown to not cause graft-versus-host disease (GVHD) in animal models and humans. We have reported that induction of MHC-mismatched mixed chimerism can cure autoimmunity in autoimmune NOD mice, but this approach has not yet been tested in animal models of MS, such as experimental autoimmune encephalomyelitis (EAE). Here, we report that MHC-mismatched mixed chimerism with C57BL/6 (H-2b) donor in SJL/J (H-2s) EAE recipients eliminates clinical symptoms and prevents relapse. This cure is demonstrated by not only disappearance of clinical signs but also reversal of autoimmunity; elimination of infiltrating T, B, and macrophage cells in the spinal cord; and regeneration of myelin sheath. The reversal of autoimmunity is associated with a marked reduction of autoreactivity of CD4+ T cells and significant increase in the percentage of Foxp3+ Treg among host-type CD4+ T cells in the spleen and lymph nodes. The latter is associated with a marked reduction of the percentage of host-type CD4+CD8+ thymocytes and an increase of Treg percentage among the CD4+CD8+ and CD4+CD8− thymocytes. Thymectomy leads to loss of prevention of EAE relapse by induction of mixed chimerism, although there is a dramatic expansion of host-type Treg cells in the lymph nodes. These results indicate that induction of MHC-mismatched mixed chimerism can restore thymic negative selection of autoreactive CD4+ T cells, augment production of Foxp3+ Treg, and cure EAE. PMID:26647186

Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury

PubMed Central

Issan, Y.; Katz, Y.; Sultan, M.; Safran, M.; Michal, Laniado-Schwartzman; Nader, G. Abraham; Kornowski, R.; Grief, F.; Pappo, O.; Hochhauser, E.

2017-01-01

Ischemia/reperfusion (I/R) injury is the main cause of primary graft dysfunction of liver allografts. Cobalt-protoporphyrin (CoPP)–dependent induction of heme oxygenase (HO)-1 has been shown to protect the liver from I/R injury. This study analyzes the apoptotic mechanisms of HO-1-mediated cytoprotection in mouse liver exposed to I/R injury. HO-1 induction was achieved by the administration of CoPP (1.5 mg/kg body weight i.p.). Mice were studied in in vivo model of hepatic segmental (70 %) ischemia for 60 min and reperfusion injury. Mice were randomly allocated to four main experimental groups (n = 10 each): (1) A control group undergoing sham operation. (2) Similar to group 1 but with the administration of CoPP 72 h before the operation. (3) Mice undergoing in vivo hepatic I/R. (4) Similar to group 3 but with the administration of CoPP 72 h before ischemia induction. When compared with the I/R mice group, in the I/R+CoPP mice group, the increased hepatic expression of HO-1 was associated with a significant reduction in liver enzyme levels, fewer apoptotic hepatocytes cells were identified by morphological criteria and by immunohistochemistry for caspase-3, there was a decreased mean number of proliferating cells (positively stained for Ki67), and a reduced hepatic expression of: C/EBP homologous protein (an index of endoplasmic reticulum stress), the NF-κB’s regulated genes (CIAP2, MCP-1 and IL-6), and increased hepatic expression of IκBa (the inhibitory protein of NF-κB). HO-1 over-expression plays a pivotal role in reducing the hepatic apoptotic IR injury. HO-1 may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation. PMID:23435964

Combining oxytocin administration and positive emotion inductions: Examining social perception and analytical performance.

PubMed

Human, Lauren J; Thorson, Katherine R; Woolley, Joshua D; Mendes, Wendy Berry

2017-04-01

Intranasal administration of the hypothalamic neuropeptide oxytocin (OT) has, in some studies, been associated with positive effects on social perception and cognition. Similarly, positive emotion inductions can improve a range of perceptual and performance-based behaviors. In this exploratory study, we examined how OT administration and positive emotion inductions interact in their associations with social and analytical performance. Participants (N=124) were randomly assigned to receive an intranasal spray of OT (40IU) or placebo and then viewed one of three videos designed to engender one of the following emotion states: social warmth, pride, or an affectively neutral state. Following the emotion induction, participants completed social perception and analytical tasks. There were no significant main effects of OT condition on social perception tasks, failing to replicate prior research, or on analytical performance. Further, OT condition and positive emotion inductions did not interact with each other in their associations with social perception performance. However, OT condition and positive emotion manipulations did significantly interact in their associations with analytical performance. Specifically, combining positive emotion inductions with OT administration was associated with worse analytical performance, with the pride induction no longer benefiting performance and the warmth induction resulting in worse performance. In sum, we found little evidence for main or interactive effects of OT on social perception but preliminary evidence that OT administration may impair analytical performance when paired with positive emotion inductions. Copyright © 2017 Elsevier Inc. All rights reserved.

Chiral Thioxanthones as Modulators of P-glycoprotein: Synthesis and Enantioselectivity Studies.

PubMed

Lopes, Ana; Martins, Eva; Silva, Renata; Pinto, Madalena M M; Remião, Fernando; Sousa, Emília; Fernandes, Carla

2018-03-10

Recently, thioxanthone derivatives were found to protect cells against toxic P-glycoprotein (P-gp) substrates, acting as potent inducers/activators of this efflux pump. The study of new P-gp chiral modulators produced from thioxanthone derivatives could clarify the enantioselectivity of this ABC transporter towards this new class of modulators. The aim of this study was to evaluate the P-gp modulatory ability of four enantiomeric pairs of new synthesized chiral aminated thioxanthones (ATxs) 1 - 8 , studying the influence of the stereochemistry on P-gp induction/ activation in cultured Caco-2 cells. The data displayed that all the tested compounds (at 20 μM) significantly decreased the intracellular accumulation of a P-gp fluorescent substrate (rhodamine 123) when incubated simultaneously for 60 min, demonstrating an increased activity of the efflux, when compared to control cells. Additionally, all of them except ATx 3 (+), caused similar results when the accumulation of the P-gp fluorescent substrate was evaluated after pre-incubating cells with the test compounds for 24 h, significantly reducing the rhodamine 123 intracellular accumulation as a result of a significant increase in P-gp activity. However, ATx 2 (-) was the only derivative that, after 24 h of incubation, significantly increased P-gp expression. These results demonstrated a significantly increased P-gp activity, even without an increase in P-gp expression. Therefore, ATxs 1 - 8 were shown to behave as P-gp activators. Furthermore, no significant differences were detected in the activity of the protein when comparing the enantiomeric pairs. Nevertheless, ATx 2 (-) modulates P-gp expression differently from its enantiomer, ATx 1 (+). These results disclosed new activators and inducers of P-gp and highlight the existence of enantioselectivity in the induction mechanism.

Proteomic Analysis of the Secretory Response of Aspergillus niger to D-Maltose and D-Xylose

PubMed Central

Ferreira de Oliveira, José Miguel P.; van Passel, Mark W. J.; Schaap, Peter J.; de Graaff, Leo H.

2011-01-01

Fungi utilize polysaccharide substrates through extracellular digestion catalyzed by secreted enzymes. Thus far, protein secretion by the filamentous fungus Aspergillus niger has mainly been studied at the level of individual proteins and by genome and transcriptome analyses. To extend these studies, a complementary proteomics approach was applied with the aim to investigate the changes in secretome and microsomal protein composition resulting from a shift to a high level secretion condition. During growth of A. niger on d-sorbitol, small amounts of d-maltose or d-xylose were used as inducers of the extracellular amylolytic and xylanolytic enzymes. Upon induction, protein compositions in the extracellular broth as well as in enriched secretory organelle (microsomal) fractions were analyzed using a shotgun proteomics approach. In total 102 secreted proteins and 1,126 microsomal proteins were identified in this study. Induction by d-maltose or d-xylose resulted in the increase in specific extracellular enzymes, such as glucoamylase A on d-maltose and β-xylosidase D on d-xylose, as well as of microsomal proteins. This reflects the differential expression of selected genes coding for dedicated extracellular enzymes. As expected, the addition of extra d-sorbitol had no effect on the expression of carbohydrate-active enzymes, compared to addition of d-xylose or d-maltose. Furthermore, d-maltose induction caused an increase in microsomal proteins related to translation (e.g., Rpl15) and vesicular transport (e.g., the endosomal-cargo receptor Erv14). Millimolar amounts of the inducers d-maltose and d-xylose are sufficient to cause a direct response in specific protein expression levels. Also, after induction by d-maltose or d-xylose, the induced enzymes were found in microsomes and extracellular. In agreement with our previous findings for d-xylose induction, d-maltose induction leads to recruitment of proteins involved in proteasome-mediated degradation. PMID:21698107

Proteomic analysis of the secretory response of Aspergillus niger to D-maltose and D-xylose.

PubMed

de Oliveira, José Miguel P Ferreira; van Passel, Mark W J; Schaap, Peter J; de Graaff, Leo H

2011-01-01

Fungi utilize polysaccharide substrates through extracellular digestion catalyzed by secreted enzymes. Thus far, protein secretion by the filamentous fungus Aspergillus niger has mainly been studied at the level of individual proteins and by genome and transcriptome analyses. To extend these studies, a complementary proteomics approach was applied with the aim to investigate the changes in secretome and microsomal protein composition resulting from a shift to a high level secretion condition. During growth of A. niger on D-sorbitol, small amounts of D-maltose or D-xylose were used as inducers of the extracellular amylolytic and xylanolytic enzymes. Upon induction, protein compositions in the extracellular broth as well as in enriched secretory organelle (microsomal) fractions were analyzed using a shotgun proteomics approach. In total 102 secreted proteins and 1,126 microsomal proteins were identified in this study. Induction by D-maltose or D-xylose resulted in the increase in specific extracellular enzymes, such as glucoamylase A on D-maltose and β-xylosidase D on D-xylose, as well as of microsomal proteins. This reflects the differential expression of selected genes coding for dedicated extracellular enzymes. As expected, the addition of extra D-sorbitol had no effect on the expression of carbohydrate-active enzymes, compared to addition of D-xylose or D-maltose. Furthermore, D-maltose induction caused an increase in microsomal proteins related to translation (e.g., Rpl15) and vesicular transport (e.g., the endosomal-cargo receptor Erv14). Millimolar amounts of the inducers D-maltose and D-xylose are sufficient to cause a direct response in specific protein expression levels. Also, after induction by D-maltose or D-xylose, the induced enzymes were found in microsomes and extracellular. In agreement with our previous findings for D-xylose induction, D-maltose induction leads to recruitment of proteins involved in proteasome-mediated degradation.

Resveratrol-Activated AMPK/SIRT1/Autophagy in Cellular Models of Parkinson's Disease

PubMed Central

Wu, Yuncheng; Li, Xinqun; Zhu, Julie Xiaohong; Xie, Wenjie; Le, Weidong; Fan, Zhen; Jankovic, Joseph; Pan, Tianhong

2011-01-01

Excessive misfolded proteins and/or dysfunctional mitochondria, which may cause energy deficiency, have been implicated in the etiopathogenesis of Parkinson's disease (PD). Enhanced clearance of misfolded proteins or injured mitochondria via autophagy has been reported to have neuroprotective roles in PD models. The fact that resveratrol is a known compound with multiple beneficial effects similar to those associated with energy metabolism led us to explore whether neuroprotective effects of resveratrol are related to its role in autophagy regulation. We tested whether modulation of mammalian silent information regulator 2 (SIRT1) and/or metabolic energy sensor AMP-activated protein kinase (AMPK) are involved in autophagy induction by resveratrol, leading to neuronal survival. Our results showed that resveratrol protected against rotenone-induced apoptosis in SH-SY5Y cells and enhanced degradation of α-synucleins in α-synuclein-expressing PC12 cell lines via autophagy induction. We found that suppression of AMPK and/or SIRT1 caused decrease of protein level of LC3-II, indicating that AMPK and/or SIRT1 are required in resveratrol-mediated autophagy induction. Moreover, suppression of AMPK caused inhibition of SIRT1 activity and attenuated protective effects of resveratrol on rotenone-induced apoptosis, further suggesting that AMPK-SIRT1-autophagy pathway plays an important role in the neuroprotection by resveratrol on PD cellular models. PMID:21778691

Regulated overexpression of interleukin 11 in the lung. Use to dissociate development-dependent and -independent phenotypes.

PubMed Central

Ray, P; Tang, W; Wang, P; Homer, R; Kuhn, C; Flavell, R A; Elias, J A

1997-01-01

Standard overexpression transgenic approaches are limited in their ability to model waxing and waning diseases and frequently superimpose development-dependent and -independent phenotypic manifestations. We used the clara cell 10-kD protein (CC10) promoter and the reverse tetracycline transactivator (rtTA) to create a lung-specific, externally regulatable, overexpression transgenic system and used this system to express human interleukin 11 (IL-11) in respiratory structures. Gene induction could be achieved in utero, in neonates and in adult animals. Moreover, gene expression could be turned off by removal of the inducing stimulus. When gene activation was initiated in utero and continued into adulthood, subepithelial airway fibrosis, peribronchiolar mononuclear nodules, and alveolar enlargement (emphysema) were noted. Induction in the mature lung caused airway remodeling and peribronchiolar nodules, but alveolar enlargement was not appreciated. In contrast, induction in utero and during the first 14 d of life caused alveolar enlargement without airway remodeling or peribronchiolar nodules. Thus, IL-11 overexpression causes abnormalities that are dependent (large alveoli) and independent (airway remodeling, peribronchiolar nodules) of lung growth and development, and the CC10-rtTA system can be used to differentiate among these effector functions. The CC10-rtTA transgenic system can be used to model waxing and waning, childhood and growth and development-related biologic processes with enhanced fidelity. PMID:9366564

Anti-inflammatory effects of theophylline, cromolyn and salbutamol in a murine model of pleurisy.

PubMed Central

Saleh, T. S.; Calixto, J. B.; Medeiros, Y. S.

1996-01-01

1. The aim of this study was to examine the effect of theophylline, cromolyn and salbutamol, three well-known anti-asthmatic drugs, on the early (4 h) and late (48 h) phases of cell migration and fluid leakage induced by carrageenin in the pleural cavity of mice. 2. In the first set of experiments, animals were pretreated (30 min) with different doses of theophylline (0.5-50 mg kg-1, i.p.), cromolyn (0.02-0.2 mg per pleural cavity) or salbutamol (0.05-50 mg kg-1, i.p.); the total and differential cell content, and also the exudate were analysed 4 h after carrageenin (1%) administration. Afterwards, in order to evaluate the time course effects of these drugs on both phases of the inflammatory reaction, one dose employed in the above protocol was chosen, to pretreat (0.5-24 h) different groups of animals. The studied parameters were evaluated 4 and 48 h after pleurisy induction. 3. Acute administration of theophylline (1-50 mg kg-1, i.p.) cromolyn (0.02-0.2 mg per pleural cavity) and salbutamol (0.5-50 mg kg-1, i.p.), 30 min prior to carrageenin, caused significant inhibition of total cell and fluid leakage in the pleural cavity at 4 h (P < 0.01). All drugs exerted a long-lasting inhibitory effect on both exudation and cell migration (P < 0.01) when administered 0.5-8 h before pleurisy induction. However, the temporal profile of the inhibitory effect induced by these drugs on the first phase of the inflammatory reaction was clearly different. Thus, the inhibitory effect induced by theophylline and cromolyn on exudation was significantly longer (up to 24 h) in comparison to their effects on cell migration (only up to 8 h). In contrast, although salbutamol when administered 30 min before pleurisy induction abolished fluid leakage (P < 0.01), this effect was not sustained in the groups pretreated for 4-8 h. In these latter groups, a significant but much smaller reduction of exudation was observed (P < 0.01), whereas the magnitude of cell migration inhibition did not vary. 4. The second phase (48 h) of the inflammatory reaction induced by carrageenin (1%) was significantly inhibited by cromolyn (0.02 mg per pleural cavity) when this drug was administered 0.5-24 h before pleurisy induction (P < 0.01). Similar results were observed when theophylline (50 mg kg-1, i.p.) was administered 0.5-4 h before the injection of the phlogistic agent (P < 0.01). Treatment of the animals with salbutamol (5 mg kg-1, i.p.), 0.5-24 h before pleurisy induction, did not inhibit either cell migration or fluid leakage. In this condition, a significant increase of these parameters was observed in the group pretreated with salbutamol 8-24 h before pleurisy induction (P < 0.01). 5. These results indicate that theophylline and cromolyn were able to inhibit the early (4 h) and late (48 h) phases of the inflammatory reaction induced by carrageenin in a murine model of pleurisy. Salbutamol was effective only against the early phase. The inhibitory effects of theophylline, cromolyn and salbutamol on the early phase of this inflammatory reaction were long-lasting, although a distinct profile of inhibition was observed among them. These findings confirm and extend previous results described in other models of asthma and support both clinical and experimental evidence suggesting that these anti-asthmatic agents exhibit marked anti-inflammatory properties. PMID:8762112

Induction chemotherapy in acute myeloid leukaemia: origins and emerging directions.

PubMed

Upadhyay, Vivek A; Fathi, Amir T

2018-03-01

This review summarizes the hallmark developments in induction chemotherapy for acute myeloid leukaemia and further describes future directions in its evolution. We describe the origin of induction chemotherapy. We also describe notable modifications and adjustments to 7+3 induction chemotherapy since its development. Finally, we describe new efforts to modify and add new agents to induction therapy, including '7+3 Plus' combinations. Induction chemotherapy remains the standard of care for the majority of patients with acute myeloid leukaemia. However, its success is limited in a subset of patients by toxicity, failure to achieve remission and potential for subsequent relapse. Novel agents such as mutant fms like tyrosine kinase 3 inhibitors, mutant isocitrate dehydrogenase inhibitors, CD33-antibody drug conjugates and liposomal formulations have demonstrated significant potential as modifications to traditional induction chemotherapy.

Issues of Exploitation of Induction Motors in the Course of Underground Mining Operations

NASA Astrophysics Data System (ADS)

Gumula, Stanisław; Hudy, Wiktor; Piaskowska-Silarska, Malgorzata; Pytel, Krzysztof

2017-09-01

Mining industry is one of the most important customers of electric motors. The most commonly used in the contemporary mining industry is alternating current machines used for processing electrical energy into mechanical energy. The operating problems and the influence of qualitative interference acting on the inputs of individual regulators to field-oriented system in the course of underground mining operations has been presented in the publication. The object of controlling the speed is a slip-ring induction motor. Settings of regulators were calculated using an evolutionary algorithm. Examination of system dynamics was performed by a computer with the use of the MATLAB / Simulink software. According to analyzes, large distortion of input signals of regulators adversely affects the rotational speed that pursued by the control system, which may cause a large vibration of the whole system and, consequently, its much faster destruction. Designed system is characterized by a significantly better resistance to interference. The system is stable with the properly selected settings of regulators, which is particularly important during the operation of machinery used in underground mining.

Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia

NASA Astrophysics Data System (ADS)

Minamino, Tohru; Christou, Helen; Hsieh, Chung-Ming; Liu, Yuxiang; Dhawan, Vijender; Abraham, Nader G.; Perrella, Mark A.; Mitsialis, S. Alex; Kourembanas, Stella

2001-07-01

Chronic hypoxia causes pulmonary hypertension with smooth muscle cell proliferation and matrix deposition in the wall of the pulmonary arterioles. We demonstrate here that hypoxia also induces a pronounced inflammation in the lung before the structural changes of the vessel wall. The proinflammatory action of hypoxia is mediated by the induction of distinct cytokines and chemokines and is independent of tumor necrosis factor- signaling. We have previously proposed a crucial role for heme oxygenase-1 (HO-1) in protecting cardiomyocytes from hypoxic stress, and potent anti-inflammatory properties of HO-1 have been reported in models of tissue injury. We thus established transgenic mice that constitutively express HO-1 in the lung and exposed them to chronic hypoxia. HO-1 transgenic mice were protected from the development of both pulmonary inflammation as well as hypertension and vessel wall hypertrophy induced by hypoxia. Significantly, the hypoxic induction of proinflammatory cytokines and chemokines was suppressed in HO-1 transgenic mice. Our findings suggest an important protective function of enzymatic products of HO-1 activity as inhibitors of hypoxia-induced vasoconstrictive and proinflammatory pathways.

RNase 7 participates in cutaneous innate control of Corynebacterium amycolatum.

PubMed

Walter, Stephanie; Rademacher, Franziska; Kobinger, Nicole; Simanski, Maren; Gläser, Regine; Harder, Jürgen

2017-10-24

Nondiphtheria corynebacteria are typical members of the skin microbiota. However, in addition to being harmless inhabitants of healthy skin commensal skin-derived corynebacteria such as C. amycolatum occasionally also cause infections. This suggests that human skin must harbor adequate mechanisms to control the growth of corynebacteria on the skin surface. Here we show that keratinocytes are able to detect the presence of C. amycolatum leading to the epidermal growth factor receptor (EGFR)-dependent induction of the antimicrobial protein RNase 7. C. amycolatum-mediated induction of RNase 7 was also confirmed in a human 3D skin equivalent. The functional relevance of these findings was demonstrated by potent antimicrobial activity of RNase 7 against C. amycolatum and C. xerosis. In addition, the capacity of human stratum corneum to restrict the growth of C. amycolatum was significantly attenuated when RNase 7 was inactivated by a specific RNase 7-neutralizing antibody. Taken together, the interaction of RNase 7 with C. amycolatum indicates that RNase 7 may function as important effector molecule to control the growth of corynebacteria on human skin.

Astrocyte-neuron lactate transport is required for long-term memory formation.

PubMed

Suzuki, Akinobu; Stern, Sarah A; Bozdagi, Ozlem; Huntley, George W; Walker, Ruth H; Magistretti, Pierre J; Alberini, Cristina M

2011-03-04

We report that, in the rat hippocampus, learning leads to a significant increase in extracellular lactate levels that derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by L-lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc, and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparison between ultrafine and fine particulate matter collected in Lebanon: Chemical characterization, in vitro cytotoxic effects and metabolizing enzymes gene expression in human bronchial epithelial cells.

PubMed

Borgie, Mireille; Dagher, Zeina; Ledoux, Frédéric; Verdin, Anthony; Cazier, Fabrice; Martin, Perrine; Hachimi, Adam; Shirali, Pirouz; Greige-Gerges, Hélène; Courcot, Dominique

2015-10-01

During the last few years, the induction of toxicological mechanisms by atmospheric ultrafine particles (UFP) has become one of the most studied topics in toxicology and a subject of huge debates. Fine particles (FP) and UFP collected at urban and rural sites in Lebanon were studied for their chemical composition and toxicological effects. UFP were found more enriched in trace elements, secondary inorganic ions, total carbon and organic compounds than FP. For toxicological analysis, BEAS-2B cells were exposed for 24, 48 and 72 h to increasing concentrations of FP, water-UFP suspension (UFPw) and UFP organic extract (UFPorg). Our findings showed that UFP caused earlier alterations of mitochondrial metabolism and membrane integrity from the lowest concentrations. Moreover, a significant induction of CYP1A1, CYP1B1 and AhRR genes expression was showed after cells exposure to UFPorg and to a lesser extent to UFPw and FP samples. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural inhibition and reactivation of Escherichia coli septation by elements of the SOS and TER pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dopazo, A.; Tormo, A.; Aldea, M.

1987-04-01

The inhibition of cell division caused by induction of the SOS pathway in Escherichia coli structurally blocks septation, as deduced from two sets of results. Potential septation sites active at the time of SOS induction became inactivated, while those initiated during the following doubling time were active. Penicillin resistance increased in wild-type UV light-irradiated cells, a behavior similar to that observed in mutants in which structural blocks were introduced by inactivation of FtsA. Potential septation sites that have been structurally blocked by either the SOS division inhibitor, furazlocillin inhibition of PBP3, or inactivation of a TER pathway component, FtsA3, couldmore » be reactivated one doubling time after removal of the inhibitory agent in the presence of an active lon gene product. Reactivation of potential septation sites blocked by the presence of an inactivated FtsA3 was significantly lower when the lon protease was not active, suggesting that Lon plays a role in the removal of inactivated TER pathway products from the blocked potential septation sites.« less

Electromagnetic heating of minor planets in the early solar system

NASA Technical Reports Server (NTRS)

Herbert, F.; Sonett, C. P.

1979-01-01

Electromagnetic processes occurring in the primordial solar system are likely to have significantly affected planetary evolution. In particular, electrical coupling of the kinetic energy of a dense T-Tauri-like solar wind into the interior of the smaller planets could have been a major driver of thermal metamorphism. Accordingly a grid of asteroid models of various sizes and solar distances was constructed using dc transverse magnetic induction theory. Plausible parameterizations with no requirement for a high environmental temperature led to complete melting for Vesta with no melting for Pallas and Ceres. High temperatures were reached in the Pallas model, perhaps implying nonmelting thermal metamorphosis as a cause of its anomalous spectrum. A reversal of this temperature sequence seems implausible, suggesting that the Ceres-Pallas-Vesta dichotomy is a natural outcome of the induction mechanism. Highly localized heating is expected to arise due to an instability in the temperature-controlled current distribution. Localized metamorphosis resulting from this effect may be relevant to the production and evolution of pallasites, the large presumed metal component of S object spectra, and the formation of the lunar magma ocean.

Enzymatic defenses against the toxicity of oxygen and of streptonigrin in Escherichia coli.

PubMed

Hassan, H M; Fridovich, I

1977-03-01

Anaerobically grown Escherichia coli K-12 contain only one superoxide dismutase and that is the iron-containing isozyme found in the periplasmic space. Exposure to oxygen caused the induction of a manganese-containing superoxide dismutase and of another, previously undescribed, superoxide dismutase, as well as of catalase and peroxidase. These inductions differed in their responsiveness towards oxygen. Thus the very low levels of oxygen present in deep, static, aerobic cultures were enough for nearly maximal induction of the manganese-superoxide dismutase. In contrast, induction of the new superoxide dismutase, catalase, and peroxidase required the much higher levels of oxygen achieved in vigorously agitated aerobic cultures. Anaerobically grown cells showed a much greater oxygen enhancement of the lethality of streptonigrin than did aerobically grown cells, in accord with the proposal that streptonigrin can serve as an intracellular source of superoxide. Anaerobically grown cells in which enzyme inductions were prevented by puromycin were damaged by exposure to air. This damage was evidenced both as a decline in viable cell count and as structural abnormalities evident under an electron microscope.

Monitored anesthesia care (MAC) sedation: clinical utility of fospropofol

PubMed Central

Harris, Eric A; Lubarsky, David A; Candiotti, Keith A

2009-01-01

Fospropofol, a phosphorylated prodrug version of the popular induction agent propofol, is hydrolyzed in vivo to release active propofol, formaldehyde, and phosphate. Pharmacodynamic studies show fospropofol provides clinically useful sedation and EEG/bispectral index suppression while causing significantly less respiratory depression than propofol. Pain at the injection site, a common complaint with propofol, was not reported with fospropofol; the major patient complaint was transitory perianal itching during the drug’s administration. Although many clinicians believe fospropofol can safely be given by a registered nurse, the FDA mandated that fospropofol, like propofol, must be used only in the presence of a trained anesthesia provider. PMID:20057894

Induced Wnt5a expression perturbs embryonic outgrowth and intestinal elongation, but is well-tolerated in adult mice.

PubMed

Bakker, Elvira R M; Raghoebir, Lalini; Franken, Patrick F; Helvensteijn, Werner; van Gurp, Léon; Meijlink, Frits; van der Valk, Martin A; Rottier, Robbert J; Kuipers, Ernst J; van Veelen, Wendy; Smits, Ron

2012-09-01

Wnt5a is essential during embryonic development, as indicated by mouse Wnt5a knockout embryos displaying outgrowth defects of multiple structures including the gut. The dynamics of Wnt5a involvement in these processes is unclear, and perinatal lethality of Wnt5a knockout embryos has hampered investigation of Wnt5a during postnatal stages in vivo. Although in vitro studies have suggested a relevant role for Wnt5a postnatally, solid evidence for a significant impact of Wnt5a within the complexity of an adult organism is lacking. We generated a tightly-regulated inducible Wnt5a transgenic mouse model and investigated the effects of Wnt5a induction during different time-frames of embryonic development and in adult mice, focusing on the gastrointestinal tract. When induced in embryos from 10.5 dpc onwards, Wnt5a expression led to severe outgrowth defects affecting the gastrointestinal tracts, limbs, facial structures and tails, closely resembling the defects observed in Wnt5a knockout mice. However, Wnt5a induction from 13.5 dpc onwards did not cause this phenotype, indicating that the most critical period for Wnt5a in embryonic development is prior to 13.5 dpc. In adult mice, induced Wnt5a expression did not reveal abnormalities, providing the first in vivo evidence that Wnt5a has no major impact on mouse intestinal homeostasis postnatally. Protein expression of Wnt5a receptor Ror2 was strongly reduced in adult intestine compared to embryonic stages. Moreover, we uncovered a regulatory process where induction of Wnt5a causes downregulation of its receptor Ror2. Taken together, our results indicate a role for Wnt5a during a restricted time-frame of embryonic development, but suggest no impact during homeostatic postnatal stages. Copyright © 2012 Elsevier Inc. All rights reserved.

The Caenorhabditis elegans SH2 domain-containing protein tyrosine phosphatase PTP-2 participates in signal transduction during oogenesis and vulval development

PubMed Central

Gutch, Michael J.; Flint, Andrew J.; Keller, James; Tonks, Nicholas K.; Hengartner, Michael O.

1998-01-01

Src homology-2 (SH2) domain-containing protein tyrosine phosphatases (SHPs) have been identified as either positive or negative regulators of signaling events downstream of receptor protein tyrosine kinases (R-PTKs). We describe here our characterization of ptp-2, a Caenorhabditis elegans gene that encodes a 668-amino-acid SHP. We isolated a recessive ptp-2 loss-of-function allele, op194, that lacks the conserved protein tyrosine phosphatase catalytic domain by screening for transposon-mediated deletion mutations. Homozygous ptp-2(op194) hermaphrodites exhibit a completely penetrant zygotic semisterile/maternal effect lethal phenotype, characterized by the presence of abnormally large oocytes in the zygotic semisterile animals. These phenotypes indicate that PTP-2 activity is essential for proper oogenesis. Gain-of-function let-60 ras alleles rescued the defects associated with ptp-2(op194), suggesting that LET-60 Ras acts downstream of, or in parallel to, PTP-2 during oogenesis. Although ptp-2 function is not required for normal vulval development, ptp-2(op194) altered significantly the vulval phenotypes caused by mutations in several genes of the inductive signaling pathway. The penetrance of the multivulva phenotype caused by loss-of-function mutations in lin-15, and gain-of-function mutations in let-23 or let-60 ras, was reduced by ptp-2(op194). Moreover, ptp-2(op194) increased the penetrance of the vulvaless phenotype conferred by a weak loss-of-function sem-5 allele. Taken together, our genetic data positions PTP-2 activity downstream of LET-23 in the vulval induction signaling pathway. Although PTP-2 functions to transmit a requisite signal during oogenesis, PTP-2 function during C. elegans vulval cell differentiation appears to be directed at regulating the overall strength of the inductive signal, which may contribute to the quantitative differences in signaling required for the proper specification of the 1°, 2°, and 3° vulval cell fates. PMID:9472025

Induction of tumor necrosis factor alpha by the group- and type-specific polysaccharides from type III group B streptococci.

PubMed Central

Mancuso, G; Tomasello, F; von Hunolstein, C; Orefici, G; Teti, G

1994-01-01

Previous studies suggested that circulating tumor necrosis factor alpha (TNF-alpha) may have a pathophysiologic role in experimental neonatal sepsis induced by group B streptococci (GBS). This study was undertaken to investigate the ability of the type III and group-specific polysaccharides of GBS to induce TNF-alpha production and TNF-alpha-dependent lethality in neonatal rats. The cytokine was detected in plasma samples by the L929 cytotoxicity assay. Intracardiac injections of either polysaccharide induced dose-dependent, transient elevations in plasma TNF-alpha levels that returned to baseline values after 5 h. The group-specific antigen induced significantly higher mean peak TNF-alpha levels than the type III antigen (125 +/- 47 versus 44 +/- 15 U/ml with 70 mg/kg of body weight). Glycogen (70 mg/kg), used as a negative control, did not induce TNF-alpha. The lipopolysaccharide-neutralizing agent polymyxin B did not decrease TNF-alpha levels induced by either polysaccharide, ruling out contamination with endotoxin as a possible cause of TNF-alpha induction. Fifty percent lethal doses of the type III and group-specific antigens given as intracardiac injections were 105 and 16 mg/kg, respectively. Salmonella endotoxin, used as a positive control, had a 50% lethal dose of 0.1 mg/kg. The lethal activities of GBS polysaccharides, as well as endotoxin, were completely prevented by pretreatment of neonatal rats with the respective specific antibodies or anti-murine TNF-alpha serum. To assess the relative importance of the type-specific substance in TNF-alpha induction by whole bacteria, two unrelated GBS transposon mutants devoid of only the type-specific capsular polysaccharide (COH1-13 and COH31-15) were employed. Each of the heat-killed unencapsulated mutants was able to produce plasma TNF-alpha level elevations or TNF-alpha-dependent lethality but was significantly less efficient in these activities than the corresponding encapsulated wild-type strain. These data suggest that the presence of type-specific material on GBS is not necessary for the stimulation of TNF-alpha production. Type III capsular polysaccharide, however, can significantly increase the ability of GBS to induce TNF-alpha. Further studies will be needed to assess the importance of TNF-alpha induction by the group- and type-specific antigens in the pathophysiology of GBS disease. PMID:8005664

Biological countermeasures in space radiation health.

PubMed

Kennedy, Ann R; Todd, Paul

2003-06-01

Exposure to the types of ionizing radiation encountered during space travel may cause a number of health-related problems, but the primary concern is related to the increased risk of cancer induction in astronauts. The major types of radiation considered to be of importance during space travel are protons and particles of high atomic number and high energy (HZE particles). It is now clear that biological countermeasures can be used to prevent or reduce the levels of biological consequences resulting from exposure to protons or HZE particles, including the induction of cancer, immunosuppression and neurological defects caused by these types of ionizing radiation. Research related to the dietary additions of agents to minimize the risks of developing health-related problems which can result from exposure to space radiations is reviewed.

Biological countermeasures in space radiation health

NASA Technical Reports Server (NTRS)

Kennedy, Ann R.; Todd, Paul

2003-01-01

Exposure to the types of ionizing radiation encountered during space travel may cause a number of health-related problems, but the primary concern is related to the increased risk of cancer induction in astronauts. The major types of radiation considered to be of importance during space travel are protons and particles of high atomic number and high energy (HZE particles). It is now clear that biological countermeasures can be used to prevent or reduce the levels of biological consequences resulting from exposure to protons or HZE particles, including the induction of cancer, immunosuppression and neurological defects caused by these types of ionizing radiation. Research related to the dietary additions of agents to minimize the risks of developing health-related problems which can result from exposure to space radiations is reviewed.

Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle.

PubMed

Ulbricht, Anna; Gehlert, Sebastian; Leciejewski, Barbara; Schiffer, Thorsten; Bloch, Wilhelm; Höhfeld, Jörg

2015-01-01

Chaperone-assisted selective autophagy (CASA) is a tension-induced degradation pathway essential for muscle maintenance. Impairment of CASA causes childhood muscle dystrophy and cardiomyopathy. However, the importance of CASA for muscle function in healthy individuals has remained elusive so far. Here we describe the impact of strength training on CASA in a group of healthy and moderately trained men. We show that strenuous resistance exercise causes an acute induction of CASA in affected muscles to degrade mechanically damaged cytoskeleton proteins. Moreover, repeated resistance exercise during 4 wk of training led to an increased expression of CASA components. In human skeletal muscle, CASA apparently acts as a central adaptation mechanism that responds to acute physical exercise and to repeated mechanical stimulation.

An Advanced simulation Code for Modeling Inductive Output Tubes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thuc Bui; R. Lawrence Ives

2012-04-27

During the Phase I program, CCR completed several major building blocks for a 3D large signal, inductive output tube (IOT) code using modern computer language and programming techniques. These included a 3D, Helmholtz, time-harmonic, field solver with a fully functional graphical user interface (GUI), automeshing and adaptivity. Other building blocks included the improved electrostatic Poisson solver with temporal boundary conditions to provide temporal fields for the time-stepping particle pusher as well as the self electric field caused by time-varying space charge. The magnetostatic field solver was also updated to solve for the self magnetic field caused by time changing currentmore » density in the output cavity gap. The goal function to optimize an IOT cavity was also formulated, and the optimization methodologies were investigated.« less

Protective role of curcumin on renal ischemia reperfusion injury via attenuating the inflammatory mediators and Caspase-3.

PubMed

Liu, F-H; Ni, W-J; Wang, G-K; Zhang, J-J

2016-09-30

Renal ischemia/reperfusion (I/R) damage may arise due to nephron sparing surgery in patient with a solitary kidney of restricted renal parenchymas. Apoptosis, inflammation and oxidative stress play a significant role in the expansion of renal dysfunction following renal I/R. The aim of the current investigation was to particularize the potential effect of curcumin against hypoxia induced renal injury. The albino Wistar rats divided into groups and each group contains six rats. They groups are normal control; disease control; curcumin (5 mg/kg per day) and another group orally treated with curcumin (10 mg/kg per day) for two weeks before induction of renal I/R. The renal and serum samples were collected and used for the biochemical estimation. The renal tissue was further used for the histopathological estimation. The result of the current investigation demonstrated that the curcumin significantly (P<0.01) attenuated I/R induced renal injury in a dose-dependent way. It also causes significant (P<0.01) reduction in the serum creatinine, blood urea nitrogen level and also suppressed the kidney injury molecules-1. Additionally, it also causes significant inhibition of the malonaldehyde, caspase-3, myeloperoxide, lactose dehydrogenase and interferon-gamma together with enhanced interlukin-10 content.

Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

PubMed

Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

2016-01-26

Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

Chlamydia Infection Across Host Species Boundaries Promotes Distinct Sets of Transcribed Anti-Apoptotic Factors

PubMed Central

Messinger, Joshua E.; Nelton, Emmalin; Feeney, Colleen; Gondek, David C.

2015-01-01

Chlamydiae, obligate intracellular bacteria, cause significant human and veterinary associated diseases. Having emerged an estimated 700-million years ago, these bacteria have twice adapted to humans as a host species, causing sexually transmitted infection (C. trachomatis) and respiratory associated disease (C. pneumoniae). The principle mechanism of host cell defense against these intracellular bacteria is the induction of cell death via apoptosis. However, in the “arms race” of co-evolution, Chlamydiae have developed mechanisms to promote cell viability and inhibit cell death. Herein we examine the impact of Chlamydiae infection across multiple host species on transcription of anti-apoptotic genes. We found mostly distinct patterns of gene expression (Mcl1 and cIAPs) elicited by each pathogen-host pair indicating Chlamydiae infection across host species boundaries does not induce a universally shared host response. Understanding species specific host-pathogen interactions is paramount to deciphering how potential pathogens become emerging diseases. PMID:26779446

Intense THz pulses cause H2AX phosphorylation and activate DNA damage response in human skin tissue

PubMed Central

Titova, Lyubov V.; Ayesheshim, Ayesheshim K.; Golubov, Andrey; Fogen, Dawson; Rodriguez-Juarez, Rocio; Hegmann, Frank A.; Kovalchuk, Olga

2013-01-01

Recent emergence and growing use of terahertz (THz) radiation for medical imaging and public security screening raise questions on reasonable levels of exposure and health consequences of this form of electromagnetic radiation. In particular, picosecond-duration THz pulses have shown promise for novel diagnostic imaging techniques. However, the effects of THz pulses on human cells and tissues thus far remain largely unknown. We report on the investigation of the biological effects of pulsed THz radiation on artificial human skin tissues. We observe that exposure to intense THz pulses for ten minutes leads to a significant induction of H2AX phosphorylation, indicating that THz pulse irradiation may cause DNA damage in exposed skin tissue. At the same time, we find a THz-pulse-induced increase in the levels of several proteins responsible for cell-cycle regulation and tumor suppression, suggesting that DNA damage repair mechanisms are quickly activated. Furthermore, we find that the cellular response to pulsed THz radiation is significantly different from that induced by exposure to UVA (400 nm). PMID:23577291

Intense THz pulses cause H2AX phosphorylation and activate DNA damage response in human skin tissue.

PubMed

Titova, Lyubov V; Ayesheshim, Ayesheshim K; Golubov, Andrey; Fogen, Dawson; Rodriguez-Juarez, Rocio; Hegmann, Frank A; Kovalchuk, Olga

2013-04-01

Recent emergence and growing use of terahertz (THz) radiation for medical imaging and public security screening raise questions on reasonable levels of exposure and health consequences of this form of electromagnetic radiation. In particular, picosecond-duration THz pulses have shown promise for novel diagnostic imaging techniques. However, the effects of THz pulses on human cells and tissues thus far remain largely unknown. We report on the investigation of the biological effects of pulsed THz radiation on artificial human skin tissues. We observe that exposure to intense THz pulses for ten minutes leads to a significant induction of H2AX phosphorylation, indicating that THz pulse irradiation may cause DNA damage in exposed skin tissue. At the same time, we find a THz-pulse-induced increase in the levels of several proteins responsible for cell-cycle regulation and tumor suppression, suggesting that DNA damage repair mechanisms are quickly activated. Furthermore, we find that the cellular response to pulsed THz radiation is significantly different from that induced by exposure to UVA (400 nm).

Alleviation of cadmium stress in Solanum lycopersicum L. by arbuscular mycorrhizal fungi via induction of acquired systemic tolerance

PubMed Central

Hashem, Abeer; Abd_Allah, E.F.; Alqarawi, A.A.; Al Huqail, Asma A.; Egamberdieva, D.; Wirth, S.

2015-01-01

Experiments were conducted to evaluate cadmium (Cd) stress-induced changes in growth, antioxidants and lipid composition of Solanum lycopersicum with and without arbuscular mycorrhizal fungi (AMF). Cadmium stress (50 μM) caused significant changes in the growth and physio-biochemical attributes studied. AMF mitigated the deleterious impact of Cd on the parameters studied. Cadmium stress increased malonaldehyde and hydrogen peroxide production but AMF reduced these parameters by mitigating oxidative stress. The activity of antioxidant enzymes enhanced under Cd treatment and AMF inoculation further enhanced their activity, thus strengthening the plant’s defense system. Proline and phenol content increased in Cd-treated as well as AMF-inoculated plants providing efficient protection against Cd stress. Cadmium treatment resulted in great alterations in the main lipid classes leading to a marked change in their composition. Cadmium stress caused a significant reduction in polyunsaturated fatty acids resulting in enhanced membrane leakage. The present study supports the use of AMF as a biological means to ameliorate Cd stress-induced changes in tomato. PMID:26981010

Effects of premedication with oral gabapentin on intraocular pressure changes following tracheal intubation in clinically normal dogs.

PubMed

Trbolova, Alexandra; Ghaffari, Masoud Selk; Capik, Igor

2017-09-19

Gabapentin is an antiepileptic drug widely approved as an add-on therapy for epilepsy treatment in human and dogs. There is a clinical impression that gabapentin is a suitable drug which attenuates the IOP elevation associated with tracheal intubation in humans. The present study performed to determine the effects of oral gabapentin on intraocular pressure (IOP) changes following tracheal intubation in dogs. Twenty adult healthy dogs were randomly assigned to treatment (n = 10) and control (n = 10) groups. Dogs in the treatment group received oral gabapentin (50 mg/kg) 2 h before induction of anesthesia and dogs in the control group received oral gelatin capsule placebo at the same time. The dogs were anesthetized with propofol 6 mg/kg, and anesthesia was maintained with a constant infusion of 0.2 mg/kg/min of propofol for 20 min. IOP were measured immediately before induction and then repeated immediately after induction, as well as 5 min, 10 min and 15 min following tracheal intubation in both groups. IOP was significantly higher immediately after induction, and 5 min after tracheal intubation when compared with IOP reading before induction in the control group. There was no statistically significant change in IOPs immediately after induction, and 5 min after tracheal intubation in comparison to the values before induction in the treatment group. Based on the findings of this study, preanesthetic oral administration of gabapentin significantly prevents an increase in the IOP associated with tracheal intubation in dogs anesthetized with propofol.

An investigation into reasoning biases, mood and cognitive state, and subclinical delusional ideation.

PubMed

Medlin, Haley; Warman, Debbie

2014-12-15

Following research on reasoning and the continuum of delusional ideation, the present study attempted to investigate the impact of different experimentally-induced states (stress, paranoia, and neutral) on the jumping-to-conclusions reasoning bias in individuals with varying levels of subclinical delusional ideation (SDI). Participants (N=117) completed a measure of subclinical delusional ideation (the Peters et al. Delusions Inventory or PDI; Peters et al., 1999); and were randomly assigned to receive one of two experimental inductions (stress or paranoia), or no experimental induction; their performance on two probabilistic reasoning tasks--one easy and one challenging--was assessed. Although no differences were found between individuals with high vs. low subclinical delusional ideation in the no induction condition or following the paranoia induction, in the stress-induction condition, individuals with high levels of subclinical delusional ideation were significantly less likely to jump to conclusions on the easy reasoning task. No significant effects emerged on the more challenging task. Assessment of post-test paranoid thinking indicated our paranoia induction did not have its intended effect. Importantly, because there was no pre-test of anxiety, paranoid thinking, or reasoning to determine if they shifted after the inductions, results need to be interpreted with caution. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Women's experience of post-term pregnancy.

PubMed

Maimburg, Rikke Damkjaer

2016-06-01

In recent years, induction of labour has become increasingly common in many countries and has moved towards an earlier gestational age. The aim of this study was to describe how low-risk pregnant women experienced post-term pregnancy in a large university hospital in Denmark Qualitative interviews were carried out with 31 low-risk pregnant women. Pregnant women passing their estimated time of birth date experienced their last days of pregnancy as a countdown to induction, not as their last days of pregnancy. Categorisation of the women's pregnancy based on medical statistics, and a focus on medical issues caused the women to feel less involved, and contributed to them being willing to negotiate an earlier induction of labour to avoid being stigmatised as pathological patients.

Various Indices for Diagnosis of Air-gap Eccentricity Fault in Induction Motor-A Review

NASA Astrophysics Data System (ADS)

Nikhil; Mathew, Lini, Dr.; Sharma, Amandeep

2018-03-01

From the past few years, research has gained an ardent pace in the field of fault detection and diagnosis in induction motors. In the current scenario, software is being introduced with diagnostic features to improve stability and reliability in fault diagnostic techniques. Human involvement in decision making for fault detection is slowly being replaced by Artificial Intelligence techniques. In this paper, a brief introduction of eccentricity fault is presented along with their causes and effects on the health of induction motors. Various indices used to detect eccentricity are being introduced along with their boundary conditions and their future scope of research. At last, merits and demerits of all indices are discussed and a comparison is made between them.

Anti-hyperalgesic activity of the aqueous and methanol extracts of the leaves of Pittosporum mannii Hook on CFA-induced persistent inflammatory pain.

PubMed

Wandji, Bibiane Aimée; Bomba, Francis Desire Tatsinkou; Nkeng-Efouet, Pepin Alango; Piegang, Basile Nganmegne; Kamanyi, Albert; Nguelefack, Télesphore Benoît

2018-02-01

Previous study showed that aqueous (AEPM) and methanol (MEPM) extracts from the leaves of Pittosporum mannii have analgesic effects in acute pain models. The present study evaluates the acute and chronic anti-hypernociceptive and anti-inflammatory effects of AEPM and MEPM in a model of persistent inflammatory pain. The third day after induction of inflammatory pain by subplantar injection of 100 µL of CFA in Wistar rats, AEPM and MEPM were administered orally (75, 150 and 300 mg/kg/day) and their anti-hyperalgesic and anti-inflammatory effects were follow in acute (1-24 h) and chronic (for 14 days) treatments. At the end of the chronic treatment, oxidative stress and liver parameters were assessed. Effects of plant extracts were also evaluated on nociception induced by Phorbol 12-Myristate 13-Acetate (PMA) and 8-bromo 3',5'-cAMP (8-Br-cAMP) in mice. AEPM and MEPM significantly reversed the mechanical hyperalgesia caused by CFA in acute and chronic treatment. Moreover, AEPM and MEPM also significantly reduced the nociception caused by PMA (60%) and 8-Br-cAMP (87%). Nevertheless, AEPM and MEPM failed to inhibit the paw edema caused by CFA. Plant extracts significantly reduced the nitric oxide content in the spinal cord and the plasmatic concentration of alanine aminotransferase. MEPM also significantly increased the glutathione content in the spinal cord. AEPM and MEPM given orally are effective in inhibiting mechanical hyperalgesia in persistent inflammatory pain caused by CFA. Their mechanisms of action seem to involve an interaction with PKC, PKA and nitric oxide pathways. These extracts might be devoid of hepatotoxic effects.

Thyroid hormone regulates the expression of the sonic hedgehog signaling pathway in the embryonic and adult Mammalian brain.

PubMed

Desouza, Lynette A; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E; Kottmann, Andreas H; Tole, Shubha; Vaidya, Vidita A

2011-05-01

Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and hyperthyroidism bidirectionally influenced Shh mRNA in embryonic forebrain signaling centers at stages before fetal thyroid hormone synthesis. Further, Smo and Ptc expression were significantly decreased in the forebrain of embryos derived from hypothyroid dams. Adult-onset thyroid hormone perturbations also regulated expression of the Shh pathway bidirectionally, with a significant induction of Shh, Ptc, and Smo after hyperthyroidism and a decline in Smo expression in the hypothyroid brain. Short-term T₃ administration resulted in a significant induction of cortical Shh mRNA expression and also enhanced reporter gene expression in Shh(+/LacZ) mice. Further, acute T₃ treatment of cortical neuronal cultures resulted in a rapid and significant increase in Shh mRNA, suggesting direct effects. Chromatin immunoprecipitation assays performed on adult neocortex indicated enhanced histone acetylation at the Shh promoter after acute T₃ administration, providing further support that Shh is a thyroid hormone-responsive gene. Our results indicate that maternal and adult-onset perturbations of euthyroid status cause robust and region-specific changes in the Shh pathway in the embryonic and adult forebrain, implicating Shh as a possible mechanistic link for specific neurodevelopmental effects of thyroid hormone.

The ratio of cancer cells to stroma after induction therapy in the treatment of non-small cell lung cancer.

PubMed

Goto, Masaki; Naito, Masahito; Saruwatari, Koichi; Hisakane, Kakeru; Kojima, Motohiro; Fujii, Satoshi; Kuwata, Takeshi; Ochiai, Atsushi; Nomura, Shogo; Aokage, Keiju; Hishida, Tomoyuki; Yoshida, Junji; Yokoi, Kohei; Tsuboi, Masahiro; Ishii, Genichiro

2017-02-01

Induction therapy induces degenerative changes of various degrees in both cancerous and non-cancerous cells of non-small cell lung cancer (NSCLC). The effect of induction therapy on histological characteristics, in particular the ratio of residual cancer cells to non-cancerous components, is unknown. Seventy-four NSCLC patients treated with induction therapy followed by surgery were enrolled. Residual cancer cells were identified using anti-pan-cytokeratin antibody (AE1/AE3). We analyzed and quantified the following three factors via digital image analysis; (1) the tumor area containing cancer cells and non-cancerous components (TA), (2) the total area of AE1/AE3 positive cancer cells (TACC), (3) the percentage of TACC to TA (%TACC). These factors were also analyzed in a matched control group (surgery alone, n = 80). The median TACC of the induction therapy group was significantly lower than that of the control group (p < 0.01). In addition, the median %TACC of the induction therapy group (5.9 %) was significantly lower than that of the control group (58.6 %) (p < 0.01). TACC had a strong positive correlation with TA in the control group (r = 0.93), but not in the induction therapy group. Conversely, TACC had a strong positive correlation with %TACC in the induction therapy group (r = 0.95), but not in the control group. Unlike the control group, the smaller the total area of residual cancer cells, the higher residual tumor contained non-cancerous components in the induction group, which may be the characteristic histological feature of NSCLC after induction therapy.

Role of P450 monooxygenases in the degradation of the endocrine-disrupting chemical nonylphenol by the white rot fungus Phanerochaete chrysosporium.

PubMed

Subramanian, Venkataramanan; Yadav, Jagjit S

2009-09-01

The white rot fungus Phanerochaete chrysosporium extensively degraded the endocrine disruptor chemical nonylphenol (NP; 100% of 100 ppm) in both nutrient-limited cultures and nutrient-sufficient cultures. The P450 enzyme inhibitor piperonyl butoxide caused significant inhibition (approximately 75%) of the degradation activity in nutrient-rich malt extract (ME) cultures but no inhibition in defined low-nitrogen (LN) cultures, indicating an essential role of P450 monooxygenase(s) in NP degradation under nutrient-rich conditions. A genome-wide analysis using our custom-designed P450 microarray revealed significant induction of multiple P450 monooxygenase genes by NP: 18 genes were induced (2- to 195-fold) under nutrient-rich conditions, 17 genes were induced (2- to 6-fold) in LN cultures, and 3 were induced under both nutrient-rich and LN conditions. The P450 genes Pff 311b (corresponding to protein identification number [ID] 5852) and Pff 4a (protein ID 5001) showed extraordinarily high levels of induction (195- and 167-fold, respectively) in ME cultures. The P450 oxidoreductase (POR), glutathione S-transferase (gst), and cellulose metabolism genes were also induced in ME cultures. In contrast, certain metabolic genes, such as five of the peroxidase genes, showed partial downregulation by NP. This study provides the first evidence for the involvement of P450 enzymes in NP degradation by a white rot fungus and the first genome-wide identification of specific P450 genes responsive to an environmentally significant toxicant.

Anesthesia with Isoflurane and Sevoflurane in the Crested Serpent Eagle (Spilornis cheela hoya): Minimum Anesthetic Concentration, Physiological Effects, Hematocrit, Plasma Chemistry and Behavioral Effects

PubMed Central

CHAN, Fang-Tse; CHANG, Geng-Ruei; WANG, Hsien-Chi; HSU, Tien-Huan

2013-01-01

ABSTRACT The initial goal of this study was to determine the minimum anesthetic concentration (MAC) for isoflurane (ISO) and sevoflurane (SEVO) for the crested serpent eagle. Next, we compared the anesthetic effects of each on the physiological effects, hematocrit, plasma chemistry values and behavior in spontaneously breathing captive adult crested serpent eagles. Sixteen eagles were randomly allocated to two groups for anesthesia with ISO (n=8) or SEVO (n=8). First, we measured the MAC values of ISO and SEVO, and four weeks later, we investigated the effect of each on the physiological effects, hematocrit (HCT) and plasma chemistry values. The MAC values of ISO and SEVO for crested serpent eagles were 1.46 ± 0.30 and 2.03 ± 0.32%, respectively. The results revealed no significant differences between the two anesthetics in induction time, while time of extubation to recovery was significantly shorter with SEVO. A time-related increase in end-tidal CO2 and decreases in body temperature and respiratory rates were observed during anesthesia with each anesthetic. There were no significant differences between the effect of the two anesthetics on heart rate, hematocrit, plasma chemistry values or respiration, although each caused minor respiration depression. We concluded that SEVO is a more effective inhalant agent than ISO for use in eagles, showing the most rapidest induction and recovery from anesthesia. PMID:23955396

Role of P450 Monooxygenases in the Degradation of the Endocrine-Disrupting Chemical Nonylphenol by the White Rot Fungus Phanerochaete chrysosporium▿

PubMed Central

Subramanian, Venkataramanan; Yadav, Jagjit S.

2009-01-01

The white rot fungus Phanerochaete chrysosporium extensively degraded the endocrine disruptor chemical nonylphenol (NP; 100% of 100 ppm) in both nutrient-limited cultures and nutrient-sufficient cultures. The P450 enzyme inhibitor piperonyl butoxide caused significant inhibition (∼75%) of the degradation activity in nutrient-rich malt extract (ME) cultures but no inhibition in defined low-nitrogen (LN) cultures, indicating an essential role of P450 monooxygenase(s) in NP degradation under nutrient-rich conditions. A genome-wide analysis using our custom-designed P450 microarray revealed significant induction of multiple P450 monooxygenase genes by NP: 18 genes were induced (2- to 195-fold) under nutrient-rich conditions, 17 genes were induced (2- to 6-fold) in LN cultures, and 3 were induced under both nutrient-rich and LN conditions. The P450 genes Pff 311b (corresponding to protein identification number [ID] 5852) and Pff 4a (protein ID 5001) showed extraordinarily high levels of induction (195- and 167-fold, respectively) in ME cultures. The P450 oxidoreductase (POR), glutathione S-transferase (gst), and cellulose metabolism genes were also induced in ME cultures. In contrast, certain metabolic genes, such as five of the peroxidase genes, showed partial downregulation by NP. This study provides the first evidence for the involvement of P450 enzymes in NP degradation by a white rot fungus and the first genome-wide identification of specific P450 genes responsive to an environmentally significant toxicant. PMID:19542331

L-Ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien

Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of L-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measuredmore » using the fluorochrome 2′,7′-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. -- Highlights: ► Besides the anti-oxidant effect, Vit. C also induces HO-1 expression in brain cells. ► Vit. C reduces METH neurotoxicity and ROS production by upregulating HO-1 expression. ► These results suggest a therapeutic potential for Vit. C in treating METH abusers.« less

Effects of heavy metals on biomarkers for oxidative stress in Griffon vulture (Gyps fulvus)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Espín, Silvia, E-mail: silvia.espin@um.es; Martínez-López, Emma, E-mail: emmaml@um.es; Jiménez, Pedro, E-mail: pjjm@um.es

Metals are involved in the formation of reactive oxygen species (ROS) which may result in metal-related oxidative stress that can lead to oxidative damage to lipids, DNA and proteins. It is necessary to understand the mechanisms of metal toxicity in wild birds, and the concentrations that cause effects on oxidative stress biomarkers. The aim of this study is to assess the concentrations of lead (Pb), cadmium (Cd), mercury (Hg), copper (Cu) and zinc (Zn) with regards to oxidative stress in blood samples of 66 Griffon vultures (Gyps fulvus) from two areas of the Autonomous Community of Valencia (East of Spain).more » The two study areas (Alcoy n=36 and Cinctorres n=30) were selected as random locations of interest that had not yet been studied, and are feeding stations where supplementary food, mainly of pork origin, is provided for vultures. Given that the two study areas are not considered polluted sites, we expected to find low metal concentrations. However, there are no known threshold concentrations at which metals can affect antioxidant systems, and low metal levels may have an effect on antioxidant biomolecules. In this study, since sampling was done at the beginning of the hunting season, the low Pb levels found in most Griffon vultures from Alcoy and Cinctorres (median=12.37 and 16.26 μg/dl, respectively) are suggestive of background levels usually found in vultures that feed on pork carcasses all year round. The ingestion of game meat with bullet fragments in carcasses or with Pb shots embedded in the flesh could be the cause of the high blood Pb concentrations found in three vultures from Cinctorres (83, 290 and 362 μg/dl). Griffon vultures feeding in Cinctorres had enhanced CAT and GST activities and tGSH concentrations, which may be interpreted as protective response against the higher TBARS levels. This study provides threshold concentrations at which metals affect antioxidant system derived from 66 samples of Griffon vulture. Blood Cd concentrations greater than 0.05 μg/dl produced an induction of 33% in GPx and of 44% in CAT activity in erythrocytes of vultures from Alcoy. Hg concentrations in blood higher than 3 μg/dl produced an induction of 10% in SOD activity. Concentrations of Pb above 15 µg/dl in blood produced an inhibition of 12.5% in GPx and 11.3% in CAT activity, and a TBARS induction of 10.7% in erythrocytes of Griffon vultures. - Highlights: • Except for 3 Griffon vultures, lead levels could be considered background levels. • Three vultures may be exposed to meat with bullet fragments (blood Pb=83–362 μg/dl). • Blood Cd levels≥0.05 μg/dl caused an induction of GPx and CAT activity (33% and 44%). • Blood Hg levels≥3 μg/dl caused an induction of 10% in SOD activity. • Blood Pb≥15 µg/dl caused an inhibition of GPx and CAT activity and a TBARS induction.« less

Reducing youth internalizing symptoms: Effects of a family-based preventive intervention on parental guilt induction and youth cognitive style

PubMed Central

McKEE, LAURA G.; PARENT, JUSTIN; FOREHAND, REX; RAKOW, AARON; WATSON, KELLY H.; DUNBAR, JENNIFER P.; REISING, MICHELLE M.; HARDCASTLE, EMILY; COMPAS, BRUCE E.

2014-01-01

This study utilized structural equation modeling to examine the associations among parental guilt induction (a form of psychological control), youth cognitive style, and youth internalizing symptoms, with parents and youth participating in a randomized controlled trial of a family-based group cognitive–behavioral preventive intervention targeting families with a history of caregiver depression. The authors present separate models utilizing parent report and youth report of internalizing symptoms. Findings suggest that families in the active condition (family-based group cognitive–behavioral group) relative to the comparison condition showed a significant decline in parent use of guilt induction at the conclusion of the intervention (6 months postbaseline). Furthermore, reductions in parental guilt induction at 6 months were associated with significantly lower levels of youth negative cognitive style at 12 months. Finally, reductions in parental use of guilt induction were associated with lower youth internalizing symptoms 1 year following the conclusion of the intervention (18 months postbaseline). PMID:24438999

Circuit analysis on the inductance evolution based on electrical signal from various type plasma focus device

NASA Astrophysics Data System (ADS)

Mohamad, Saiful Najmee; Ismail, Fairuz Diana; Noorden, Ahmad Fakhrurrazi Ahmad; Haider, Zuhaib; Ali, Jalil

2017-03-01

Numerous configurations of plasma focus devices (PFD) have been introduced around the globe. The distinct electrode configuration of the PFD will give out different inductance profile. A circuit analysis has been done to study on the significant difference between the inductance evolution in a coaxial discharge based on various published results of PFD. The discharge current signal, tube voltage and current derivative of the particular shots from distinct PFD was digitized and analyze. The investigation was piloted for three different types of PFD. It was observed that there is a significant difference for the normalize inductance profile during the discharge between the individual PFD with different electrode configuration. The depletion of the radial start current with the normalised inductance development for Mather type (PF-1000) is found to be 25.9% from static discharge. The current depletion continues to drop 1.1% and 1.3% more for a Spherical type (PNK-13) and Filippov type (PF-3) respectively.

[In case of fetal macrosomia, the best strategy is the induction of labor at 38 weeks of gestation].

PubMed

Rozenberg, P

2016-11-01

Macrosomic fetuses are at increased risk of obstetric complications, and notably shoulder dystocia, responsible for a severe neonatal morbidity. In case of fetal macrosomia, three options are: (i) the elective cesarean delivery, but this is recommended only when the estimated fetal weight is≥4500g for diabetic women and 5000g for non-diabetic women; (ii) the expectative management, but children with birth weight≥4500 had significantly increased risk of perinatal mortality, neonatal asphyxia, trauma, and cesarean delivery; (iii) the induction of labor which, reducing the possibility of fetal growth, reduce the risk of cesarean delivery for cephalopelvic disproportion and shoulder dystocia. As 2 former trials did not show maternal or neonatal benefit with induction of labor for fetal macrosomia, it was therefore not recommended. However, these 2 studies had small sample size (273 and 40 women) and a methodology limiting their ability to show a difference, justifying to achieve a large multicentre randomized controlled trial. This trial was performed by Boulvain et al. and the results published in 2015 in the Lancet. Inclusion criteria were: a singleton pregnancy in cephalic presentation and a suspected fetal macrosomia defined by an ultrasound estimated weight>95th percentile between 36 and 38 weeks. Women were randomly assigned to receive induction of labor within 3 days between 37 +0  and 38 +6  weeks of gestation, or expectant management. Expectant management continued until either spontaneous labour or diagnosis of a condition necessitating induction. The primary outcome was a composite of clinically significant shoulder dystocia, fracture of the clavicle, brachial plexus injury, intracranial haemorrhage, or death. Baseline characteristics were similar between groups. The mean birth weight (±SD) was 3831 (±324) g in the induction group 4118 (±392) g in the expectant group. Induction of labor significantly reduced the risk of shoulder dystocia or associated morbidity (8/407; 2 %) compared with expectant management (25/411; 6 %); P=0.004. The number needed to treat was 25 (95 % CI: 15-70). The incidence of caesarean section and operative vaginal delivery did not differ significantly between the groups. The likelihood of spontaneous vaginal delivery increased significantly in the induction of labor group (59 % vs. 52 %, RR: 1.14; 95 % CI: 1.01-1.29). In all, the results of the Boulvain et al. trial justify to propose an induction of labor in cases of suspected macrosomia>95th percentile: the induction of labor reduced the risk of severe shoulder dystocia, and does not increase the risk of cesarean section. It even increases the likelihood of spontaneous vaginal delivery. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The Effects of Leucine, Zinc, and Chromium Supplements on Inflammatory Events of the Respiratory System in Type 2 Diabetic Rats

PubMed Central

Kolahian, Saeed; Sadri, Hassan; Shahbazfar, Amir Ali; Amani, Morvarid; Mazadeh, Anis; Mirani, Mehdi

2015-01-01

Diabetes mellitus is a major cause of serious micro- and macrovascular diseases that affect nearly every system in the body, including the respiratory system. Non-enzymatic protein glycation due to hyperglycaemic stress has fundamental implications due to the large capillary network and amount of connective tissue in the lung. The current study was designed to determine whether leucine, zinc, and chromium supplementations influence the function and histological structure of the respiratory tract in a rat model of type 2 diabetes. Seventy-seven rats were divided into eleven groups, consisting of 7 animals each. One group served as negative control and insulin and glibenclamide were used as positive control drugs. Thus, eight groups received the nutritional supplements alone or in combination with each other. Nutritional supplements and glibenclamide were added to the drinking water and neutral protamine Hagedorn insulin was subcutaneously injected during the 4 weeks of treatment period. The induction of type 2 diabetes in the rats caused an infiltration of mononuclear cells and edema in the submucosa of the trachea and lung, severe fibrosis around the vessels and airways, and perivascular and peribronchial infiltration of inflammatory cells and fibrin. In the diabetic group, the total inflammation score and Reid index significantly increased. Diabetes induction significantly reduced the total antioxidant status and elevated the lipid peroxidation products in the serum, lung lavage and lung tissue of the diabetic animals. Treatment with nutritional supplements significantly decreased the histopathological changes and inflammatory indices in the diabetic animals. Supplementation of diabetic rats with leucine, zinc, and chromium, alone and in combination, significantly increased the total antioxidant status and lipid peroxidation level in the diabetic animals. The nutritional supplements improved the enzymatic antioxidant activity of catalase, glutathione peroxidase, myeloperoxidase, and superoxide dismutase in the diabetic rats. The present results demonstrate beneficial effects and amelioration of inflammation in the respiratory system of type 2 diabetic rats by leucine, zinc, and chromium supplements, probably due to their hypoglycaemic and antioxidant properties. Using safe and effective nutritional supplements, such as leucine, chromium and zinc, to replace proven conventional medical treatments may help to control diabetes and/or its complications. PMID:26185997

Platelet closure time in anesthetized Greyhounds with hemorrhagic shock treated with hydroxyethyl starch 130/0.4 or 0.9% sodium chloride infusions.

PubMed

McBride, Duana; Hosgood, Giselle; Raisis, Anthea; Smart, Lisa

2016-07-01

To measure platelet closure time (PCT) in dogs during controlled hemorrhagic shock and after fluid resuscitation with hydroxyethyl starch (HES) 130/0.4 or 0.9% sodium chloride. Experimental interventional study. University veterinary teaching hospital. Eleven healthy Greyhounds. Dogs were anesthetized and had 48 mL/kg of blood removed to induce hemorrhagic shock. Dogs received 20 mL/kg of HES 130/0.4 (n = 6) or 80 mL/kg of 0.9% sodium chloride (NaCl; n = 5) intravenously over 20 minutes. PCT was measured using the Platelet Function Analyzer-100 with collagen and adenosine-diphosphate cartridges at: T0 = 60 minutes after induction of anesthesia prior to hemorrhage, T1 = during hemorrhagic shock, and T2 = 40 minutes after completion of fluid bolus. Packed cell volume and platelet count were concurrently measured. Hemorrhagic shock did not significantly change PCT, with no difference between T0 and T1. Both the HES 130/0.4 and 0.9% NaCl group had a significantly increased mean PCT at T2 of 91.4 seconds (95% CI 69.3-113.4) and 95.5 seconds (95% CI 78.2-112.8), respectively, compared to T1. The magnitude of change was significantly greater for the 0.9% NaCl group than the HES 130/0.4 group. There was no difference in the magnitude of change in PCV and platelet count between the 2 groups. The PCV and platelet count were >25% and >100,000/μL, respectively, in all dogs, except for dogs in the HES 130/0.4 group at T2 where platelet counts were <100,000/μL. Controlled hemorrhagic shock in Greyhounds under anesthesia did not cause a significant change in PCT. Both HES 130/0.4 and 0.9% NaCl administration after induction of shock increased PCT. These results do not support that HES 130/0.4 causes relevant platelet dysfunction beyond hemodilution. © Veterinary Emergency and Critical Care Society 2016.

Induction of Mitochondrial Reactive Oxygen Species Production by Itraconazole, Terbinafine, and Amphotericin B as a Mode of Action against Aspergillus fumigatus.

PubMed

Shekhova, Elena; Kniemeyer, Olaf; Brakhage, Axel A

2017-11-01

Drug resistance in fungal pathogens is of incredible importance to global health, yet the mechanisms of drug action remain only loosely defined. Antifungal compounds have been shown to trigger the intracellular accumulation of reactive oxygen species (ROS) in human-pathogenic yeasts, but the source of those ROS remained unknown. In the present study, we examined the role of endogenous ROS for the antifungal activity of the three different antifungal substances itraconazole, terbinafine, and amphotericin B, which all target the fungal cell membrane. All three antifungals had an impact on fungal redox homeostasis by causing increased intracellular ROS production. Interestingly, the elevated ROS levels induced by antifungals were abolished by inhibition of the mitochondrial respiratory complex I with rotenone. Further, evaluation of lipid peroxidation using the thiobarbituric acid assay revealed that rotenone pretreatment decreased ROS-induced lipid peroxidation during incubation of Aspergillus fumigatus with itraconazole and terbinafine. By applying the mitochondrion-specific lipid peroxidation probe MitoPerOx, we also confirmed that ROS are induced in mitochondria and subsequently cause significant oxidation of mitochondrial membrane in the presence of terbinafine and amphotericin B. To summarize, our study suggests that the induction of ROS production contributes to the ability of antifungal compounds to inhibit fungal growth. Moreover, mitochondrial complex I is the main source of deleterious ROS production in A. fumigatus challenged with antifungal compounds. Copyright © 2017 American Society for Microbiology.

The cyclic AMP cascade is altered in the fragile X nervous system.

PubMed

Kelley, Daniel J; Davidson, Richard J; Elliott, Jamie L; Lahvis, Garet P; Yin, Jerry C P; Bhattacharyya, Anita

2007-09-26

Fragile X syndrome (FX), the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP). Although research efforts have focused on FMRP's impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 3', 5'-monophosphate (cAMP) cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in platelets and in brains of fmr1 knockout mice are substantially reduced. Cyclic AMP induction is also significantly reduced in human FX neural cells. Furthermore, cAMP production is decreased in the heads of FX Drosophila and this defect can be rescued by reintroduction of the dfmr gene. Our results indicate that a robust defect in cAMP production in FX is conserved across species and suggest that cAMP metabolism may serve as a useful biomarker in the human disease population. Reduced cAMP induction has implications for the underlying causes of FX and autism spectrum disorders. Pharmacological agents known to modulate the cAMP cascade may be therapeutic in FX patients and can be tested in these models, thus supplementing current efforts centered on mGluR signaling.

Influence of mild traumatic brain injury during pediatric stage on short-term memory and hippocampal apoptosis in adult rats.

PubMed

Park, Mi-Sook; Oh, Hyean-Ae; Ko, Il-Gyu; Kim, Sung-Eun; Kim, Sang-Hoon; Kim, Chang-Ju; Kim, Hyun-Bae; Kim, Hong

2014-06-01

Traumatic brain injury (TBI) is a leading cause of neurological deficit in the brain, which induces short- and long-term brain damage, cognitive impairment with/without structural alteration, motor deficits, emotional problems, and death both in children and adults. In the present study, we evaluated whether mild TBI in childhood causes persisting memory impairment until adulthood. Moreover, we investigated the influence of mild TBI on memory impairment in relation with hippocampal apoptosis. For this, step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and immunohistochemistry for caspase-3 were performed. Male Sprague-Dawley rats were used in the experiments. The animals were randomly divided into two groups: sham-operation group and TBI-induction group. The mild TBI model was created with an electromagnetic contusion device activated at a velocity of 3.0 m/sec. The results showed that mild TBI during the pediatric stage significantly decreased memory retention. The numbers of TUNEL-positive and caspase-3-positive cells were increased in the TBI-induction group compared to those in the sham-operation group. Defective memory retention and apoptosis sustained up to the adult stage. The present results shows that mild TBI induces long-lasting cognitive impairment from pediatric to adult stages in rats through the high level of apoptosis. The finding of this study suggests that children with mild TBI may need intensive treatments for the reduction of long-lasting cognitive impairment by secondary neuronal damage.

Induction of labor in grand multiparous women with previous cesarean delivery: how safe is this?

PubMed

Chibber, Rachana; Al-Harmi, Jehad; Foda, Mohamed; Mohammed K, Zeinab; Al-Saleh, Eyad; Mohammed, Asiya Tasneem

2015-02-01

To compare the outcome of induced and spontaneous labor in grand multiparous women with one previous lower segment cesarean section (CS), so that the safety of labor induction could be assessed. In 102 women (study group), labor was induced and the outcome was compared with 280 women (control group) who went into spontaneous labor. All 382 women were grand multiparous and had one previous CS. There were no significant difference in oxytocin augmentation, CS, scar dehiscence, fetal birth weight or apgar scores between groups. There was one neonatal death, two still births, one early neonatal death and one congenital malformation in the study group and this was not significant. There was no significant difference in vaginal birth in the study (80.9%) and the control group (83.8%). In this moderate-sized study, induction of labor may be a safe option in grand multiparous women, if there is no absolute induction for repeating CS.

Electrohysterographic characterization of the uterine myoelectrical response to labor induction drugs.

PubMed

Benalcazar-Parra, Carlos; Ye-Lin, Yiyao; Garcia-Casado, Javier; Monfort-Orti, Rogelio; Alberola-Rubio, Jose; Perales, Alfredo; Prats-Boluda, Gema

2018-06-01

Labor induction is a common practice to promote uterine contractions and labor onset. Uterine electrohysterogram (EHG) has proved its suitability for characterizing the uterus electrophysiological condition in women with spontaneous labor. The aim of this study was to characterize and compare uterine myoelectrical activity during the first 4 h in response to labor induction drugs, Misoprostol (G1) and Dinoprostone (G2), by analyzing the differences between women who achieved active phase of labor and those who did not (successful and failed inductions). A set of temporal, spectral and complexity parameters were computed from the EHG-bursts. As for successful inductions, statistical significant and sustained increases with respect to basal period were obtained for EHG amplitude, mean frequency, uterine activity index (UAI) and Teager, after 60' for the G1 group; duration, amplitude, number of contractions and UAI for the G2 group, after 120'. Moreover, Teager showed statistical significant and sustained differences between successful and failed inductions (1.43 ± 1.45 µV 2. Hz 2. 10 5  vs. 0.40 ± 0.26 µV 2. Hz 2. 10 5 after 240') for the G1 group, but not in the G2 group, probably due to the slower pharmacokinetics of this drug. These results revealed that EHG could be useful for successful induction prediction in the early stages of induction, especially when using Misoprostol. Copyright © 2018 Elsevier Ltd. All rights reserved.

Baseline Characteristics of Patients Predicting Suitability for Rapid Naltrexone Induction

PubMed Central

Mogali, Shanthi; Khan, Nabil A.; Drill, Esther S.; Pavlicova, Martina; Sullivan, Maria A.; Nunes, Edward; Bisaga, Adam

2015-01-01

Background and Objectives Extended-release (XR) injection naltrexone has proved promising in the treatment of opioid dependence. Induction onto naltrexone is often accomplished with a procedure known as rapid naltrexone induction. The purpose of this study was to evaluate pre-treatment patient characteristics as predictors of successful completion of a rapid naltrexone induction procedure prior to XR naltrexone treatment. Methods A chart review of 150 consecutive research participants (N = 84 completers and N = 66 non-completers) undergoing a rapid naltrexone induction with the buprenorphone-clonidine procedure were compared on a number of baseline demographic, clinical and psychosocial factors. Logistic regression was used to identify client characteristics that may predict successful initiation of naltrexone after a rapid induction-detoxification. Results Patients who failed to successfully initiate naltrexone were younger (AOR: 1.040, CI: 1.006, 1.075), and using 10 or more bags of heroin (or equivalent) per day (AOR: 0.881, CI: 0.820, 0.946). Drug use other than opioids was also predictive of failure to initiate naltrexone in simple bivariate analyses, but was no longer significant when controlling for age and opioid use level. Conclusions Younger age, and indicators of greater substance dependence severity (more current opioid use, other substance use) predict difficulty completing a rapid naltrexone induction procedure. Such patients might require a longer period of stabilization and/or more gradual detoxification prior to initiating naltrexone. Scientific Significance Our study findings identify specific characteristics of patients who responded positively to rapid naltrexone induction. PMID:25907815

Improving Performance and Operational Stability of Porcine Interferon-α Production by Pichia pastoris with Combinational Induction Strategy of Low Temperature and Methanol/Sorbitol Co-feeding.

PubMed

Gao, Min-Jie; Zhan, Xiao-Bei; Gao, Peng; Zhang, Xu; Dong, Shi-Juan; Li, Zhen; Shi, Zhong-Ping; Lin, Chi-Chung

2015-05-01

Various induction strategies were investigated for effective porcine interferon-α (pIFN-α) production by Pichia pastoris in a 10 L fermenter. We found that pIFN-α concentration could be significantly improved with the strategies of low-temperature induction or methanol/sorbitol co-feeding. On this basis, a combinational strategy of induction at lower temperature (20 °C) with methanol/sorbitol co-feeding has been proposed for improvement of pIFN-α production. The results reveal that maximal pIFN-α concentration and antiviral activity reach the highest level of 2.7 g/L and 1.8 × 10(7) IU/mg with the proposed induction strategy, about 1.3-2.1 folds higher than those obtained with other sub-optimal induction strategies. Metabolic analysis and online multi-variable measurement results indicate that energy metabolic enrichment is responsible for the performance enhancement of pIFN-α production, as a large amount of ATP could be simultaneously produced from both formaldehyde oxidation pathway in methanol metabolism and tricarboxylic acid (TCA) cycle in sorbitol metabolism. In addition, the proposed combinational induction strategy enables P. pastoris to be resistant to high methanol concentration (42 g/L), which conceivably occur associating with the error-prone methanol over-feeding. As a result, the proposed combinational induction strategy simultaneously increased the targeted protein concentration and operational stability leading to significant improvement of pIFN-α production.

Carvedilol: relation between antioxidant activity and inhibition of the mitochondrial permeability transition.

PubMed

Oliveira, Paulo J; Esteves, Telma; Rolo, Anabela P; Monteiro, Pedro; Gonçalves, Lino; Palmeira, Carlos M; Moreno, António J

2003-01-01

The mitochondrial permeability transition (MPT) is an event related to severe oxidative stress (for example, during myocardial ischemia and reperfusion) and excessive mitochondrial calcium accumulation, also being implicated in cell death. In this study, we compared the effect of carvedilol on the cardiac MPT induced by calcium and phosphate (Ca/Pi) and calcium/carboxyatractyloside (Ca/Catr). Oxidative stress plays a major role in MPT induction by Ca/Pi, leading to the oxidation of protein thiol groups, in contrast with Ca/Catr, where such oxidation is secondary to MPT induction and is not caused by oxidative stress. Mitochondria were isolated from rat hearts and parameters related to MPT induction were evaluated (n = 5 for each inducer): mitochondrial swelling and oxidation of protein thiol groups (both measured by spectrophotometry). Using Ca/Pi, carvedilol protected mitochondria from MPT induction, particularly in its high conductance form. Its effect was demonstrated by analyzing the decrease in mitochondrial swelling amplitude. Simultaneously, we observed inhibition of protein thiol group oxidation (p < 0.001). By contrast, carvedilol did not show any protective effect with Ca/Catr. Carvedilol was only effective against the MPT when the oxidation of protein thiol groups was the cause and not the consequence of the MPT phenomenon. The results clearly show that during myocardial aggressions (ischemia and reperfusion, for example), the protective effect of carvedilol is primarily due to an antioxidant mechanism, inhibiting the production and effects of reactive oxygen species.

Autophagy induction by leptin contributes to suppression of apoptosis in cancer cells and xenograft model: Involvement of p53/FoxO3A axis

PubMed Central

Nepal, Saroj; Kim, Mi Jin; Hong, Jin Tae; Kim, Sang Hyun; Sohn, Dong-Hwan; Lee, Sung Hee; Song, Kyung; Choi, Dong Young; Lee, Eung Seok; Park, Pil-Hoon

2015-01-01

Leptin, a hormone mainly produced from adipose tissue, has been shown to induce proliferation of cancer cells. However, the molecular mechanisms underlying leptin-induced tumor progression have not been clearly elucidated. In the present study, we investigated the role of autophagy in leptin-induced cancer cell proliferation using human hepatoma (HepG2) and breast cancer cells (MCF-7), and tumor growth in a xenograft model. Herein, we showed that leptin treatment caused autophagy induction as assessed by increase in expression of autophagy-related genes, including beclin-1, Atg5 and LC3 II, further induction of autophagosome formation and autophagic flux. Interestingly, inhibition of autophagic process by treatment with inhibitors and LC3B gene silencing blocked leptin-induced increase in cell number and suppression of apoptosis, indicating a crucial role of autophagy in leptin-induced tumor progression. Moreover, gene silencing of p53 or FoxO3A prevented leptin-induced LC3 II protein expression, suggesting an involvement of p53/FoxO3A axis in leptin-induced autophagy activation. Leptin administration also accelerated tumor growth in BALB/c nude mice, which was found to be autophagy dependent. Taken together, our results demonstrate that leptin-induced tumor growth is mediated by autophagy induction and autophagic process would be a promising target to regulate development of cancer caused by leptin production. PMID:25704884

Ferulic acid ameliorates TNBS-induced ulcerative colitis through modulation of cytokines, oxidative stress, iNOs, COX-2, and apoptosis in laboratory rats

PubMed Central

Sadar, Smeeta S.; Vyawahare, Niraj S.; Bodhankar, Subhash L.

2016-01-01

Ulcerative colitis (UC) is a chronic immune-inflammatory disorder characterized by oxido-nitrosative stress, the release of pro-inflammatory cytokines and apoptosis. Ferulic acid (FA), a phenolic compound is considered to possess potent antioxidant, anti-apoptotic and anti-inflammatory activities. The aim is to evaluate possible mechanism of action of FA against trinitrobenzensulfonic acid (TNBS) induced ulcerative colitis (UC) in rats. UC was induced in Sprague-Dawley rats (150-200 g) by intrarectal administration of TNBS (100 mg/kg). FA was administered (10, 20 and 40 mg/kg, p.o.) for 14 days after colitis was induced. Various biochemical, molecular and histological changes were assessed in the colon. Intrarectal administration of TNBS caused significant induction of ulcer in the colon with an elevation of oxido-nitrosative stress, myeloperoxidase and hydroxyproline activity in the colon. Administration of FA (20 and 40 mg/kg) significantly decrease oxido-nitrosative stress, myeloperoxidase, and hydroxyproline activities. Up-regulated mRNA expression of TNF-α, IL-1β, IL-6, COX-2, and iNOs, as well as down-regulated IL-10 mRNA expressions after TNBS administration, were significantly inhibited by FA (20 and 40 mg/kg) treatment. Flow cytometric analysis revealed that intrarectal administration of TNBS-induced significantly enhanced the colonic apoptosis whereas administration of FA (20 and 40 mg/kg) significantly restored the elevated apoptosis. FA administration also significantly restored the histopathological aberration induced by TNBS. The findings of the present study demonstrated that FA ameliorates TNBS-induced colitis via inhibition of oxido-nitrosative stress, apoptosis, proinflammatory cytokines production, and down- regulation of COX-2 synthesis. Graphical Abstract: TNBS caused activation of T cells which interact with CD40 on antigen presenting cells i.e. dendritic cells (DC) that induce the key Interleukin 12 (IL-12)-mediated Th1 T cell immune inflammatory response. It releases interferon-γ (IFN-γ), which in turn induces macrophages (MAC) to produce TNF-α and other pro-inflammatory cytokines (e.g., IL-1β, IL-6). This inflammatory influx resulted in induction of ulcerative colitis (UC). Administration of FA may inhibit this IFN-γ induced inflammatory cascade via a decrease in the release of pro-inflammatory cytokines to ameliorate TNBS-induced colitis. PMID:27822176

High Concentration of Benzyladenine Solution Stimulates Anthers for Inducing Callus in Ricinus Communis L.

NASA Astrophysics Data System (ADS)

Liu, Ying; Yan, Shuying; Yang, Fuguang; Li, Dongliang; Tang, Jianian; Liu, Guoxuan; Lin, Shiwan; Niu, Sufang; Yang, Yali

2017-12-01

An high-frequency protocol for induction of callus from anther explants of Ricinus communis was described. When anther explants of R. communis was cultured directly onto medium containing 6-benzylaminopurine (BA) induced formation of only poor quality callus that had a low induction frequency of anther callus (10.67%). However, treating the anther explants with high concentrations (7.5-120 mg/L) of BA solution for short time periods (5-80 min) helped to improve the induction frequency and enhance the quality of the callus formation significantly. The best callus induction (41.25%) was observed when anther explants were treated with 15 mg/L BA solution for 10 min before being inoculated onto hormone-free Murashige and Skoog (MS) medium for 30 days. In order to further optimize the culture system, after treated with 15 mg/L BA for 10 min, anther explants were inoculated on the hormone-free MS medium contained concentrations of sodium nitroprusside (SNP). The results showed that SNP significantly promoted the response of callus induction, especially when 8 mg/L SNP was applied, the the highest percentage of callus induction (60.37%) were gained.

Numerical Studies of Three-dimensional Breakdown in Trailing Vortex Wakes

NASA Technical Reports Server (NTRS)

Evans, P. F.; Hackett, J. E.

1976-01-01

Finite element, three dimensional relaxation methods are used to calculate the development of vortex wakes behind aircraft for a considerable downstream distance. The inclusion of a self-induction term in the solution, dependent upon local curvature and vortex core radius, permits calculation of finite lifetimes for systems for which infinite life would be predicted two dimensionally. The associated computer program is described together with single-pair, twin-pair, and multiple-pair studies carried out using it. It is found, in single-pair studies, that there is a lower limit to the wavelengths at which the Crow-type of instability can occur. Below this limit, self-induction effects cause the plane of the disturbance waves to rotate counter to the vortex direction. Self induction in two dimensionally generated twin spiral waves causes an increase in axial length which becomes more marked with decreasing initial wavelength. The time taken for vortex convergence toward the center plane is correspondingly increased. The limited parametric twin-pair study performed suggests that time-to-converge increases with increasing flap span. Limited studies of Boeing 747 configurations show correct qualitative response to removal of the outer flap and to gear deployment, as compared with wind tunnel and flight test experience.

Inflammatory cause of metabolic syndrome via brain stress and NF-κB.

PubMed

Cai, Dongsheng; Liu, Tiewen

2012-02-01

Metabolic syndrome, a network of medical disorders that greatly increase the risk for developing metabolic and cardiovascular diseases, has reached epidemic levels in many areas of today's world. Despite this alarming medicare situation, scientific understandings on the root mechanisms of metabolic syndrome are still limited, and such insufficient knowledge contributes to the relative lack of effective treatments or preventions for related diseases. Recent interdisciplinary studies from neuroendocrinology and neuroimmunology fields have revealed that overnutrition can trigger intracellular stresses to cause inflammatory changes mediated by molecules that control innate immunity. This type of nutrition-related molecular inflammation in the central nervous system, particularly in the hypothalamus, can form a common pathogenic basis for the induction of various metabolic syndrome components such as obesity, insulin resistance, and hypertension. Proinflammatory NF-κB pathway has been revealed as a key molecular system for pathologic induction of brain inflammation, which translates overnutrition and resulting intracellular stresses into central neuroendocrine and neural dysregulations of energy, glucose, and cardiovascular homeostasis, collectively leading to metabolic syndrome. This article reviews recent research advances in the neural mechanisms of metabolic syndrome and related diseases from the perspective of pathogenic induction by intracellular stresses and NF-κB pathway of the brain.

Dimethoxycurcumin-induced cell death in human breast carcinoma MCF7 cells: evidence for pro-oxidant activity, mitochondrial dysfunction, and apoptosis.

PubMed

Kunwar, A; Jayakumar, S; Srivastava, A K; Priyadarsini, K I

2012-04-01

The factors responsible for the induction of cell death by dimethoxycurcumin (Dimc), a synthetic analog of curcumin, were assessed in human breast carcinoma MCF7 cells. Initial cytotoxic studies with both curcumin and Dimc using MTT assay indicated their comparable effects. Further, the mechanism of action was explored in terms of oxidative stress, mitochondrial dysfunction, and modulation in the expression of proteins involved in cell cycle regulation and apoptosis. Dimc (5-50 μM) caused generation of reactive oxygen species, reduction in glutathione level, and induction of DNA damage. The mitochondrial dysfunction induced by Dimc was evidenced by the reduction in mitochondrial membrane potential and decrease in cellular energy status (ATP/ADP) monitored by HPLC analysis. The observed decrease in ATP was also supported by the significant suppression of different (α, β, γ, and ε) subunits of ATP synthase. The cytotoxic effect of Dimc was further characterized in terms of induction of S-phase cell cycle arrest and apoptosis, and their relative contribution was found to vary with the treatment concentration of Dimc. The S-phase arrest and apoptosis could also be correlated with the changes in the expressions of cell cycle proteins like p53, p21, CDK4, and cyclin-D1 and apoptotic markers like Bax and Bcl-2. Overall, the results demonstrated that Dimc induced cell death in MCF7 cells through S-phase arrest and apoptosis.

Stronger proteasomal inhibition and higher CHOP induction are responsible for more effective induction of paraptosis by dimethoxycurcumin than curcumin

PubMed Central

Yoon, M J; Kang, Y J; Lee, J A; Kim, I Y; Kim, M A; Lee, Y S; Park, J H; Lee, B Y; Kim, I A; Kim, H S; Kim, S-A; Yoon, A-R; Yun, C-O; Kim, E-Y; Lee, K; Choi, K S

2014-01-01

Although curcumin suppresses the growth of a variety of cancer cells, its poor absorption and low systemic bioavailability have limited its translation into clinics as an anticancer agent. In this study, we show that dimethoxycurcumin (DMC), a methylated, more stable analog of curcumin, is significantly more potent than curcumin in inducing cell death and reducing the clonogenicity of malignant breast cancer cells. Furthermore, DMC reduces the tumor growth of xenografted MDA-MB 435S cells more strongly than curcumin. We found that DMC induces paraptosis accompanied by excessive dilation of mitochondria and the endoplasmic reticulum (ER); this is similar to curcumin, but a much lower concentration of DMC is required to induce this process. DMC inhibits the proteasomal activity more strongly than curcumin, possibly causing severe ER stress and contributing to the observed dilation. DMC treatment upregulates the protein levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and Noxa, and the small interfering RNA-mediated suppression of CHOP, but not Noxa, markedly attenuates DMC-induced ER dilation and cell death. Interestingly, DMC does not affect the viability, proteasomal activity or CHOP protein levels of human mammary epithelial cells, suggesting that DMC effectively induces paraptosis selectively in breast cancer cells, while sparing normal cells. Taken together, these results suggest that DMC triggers a stronger proteasome inhibition and higher induction of CHOP compared with curcumin, giving it more potent anticancer effects on malignant breast cancer cells. PMID:24625971

Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis.

PubMed

Vickers, Adrian D; Ainsworth, Claire; Mody, Reema; Bergman, Annika; Ling, Caroline S; Medjedovic, Jasmina; Smyth, Michael

2016-01-01

Biological therapies are increasingly used to treat ulcerative colitis (UC). To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy. A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance. Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI)]: 2.19 [1.35-3.55]), clinical remission (OR [95% CrI]: 2.81 [1.49-5.49]), and mucosal healing (OR [95% CrI]: 2.23 [1.21-4.14]); there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients 'straight through'. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14-9.20], golimumab 2.33 [1.04-5.41], and adalimumab 3.96 [1.67-9.84]). In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36-41.0]). This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All biologic treatments were effective for UC during induction. Vedolizumab demonstrated possible clinical benefits in the maintenance setting versus all comparators, irrespective of prior anti-TNF exposure and after adjusting for differences in study design.

Sulfur mustard analog, 2-chloroethyl ethyl sulfide-induced skin injury involves DNA damage and induction of inflammatory mediators, in part via oxidative stress, in SKH-1 hairless mouse skin

PubMed Central

Jain, Anil K.; Tewari-Singh, Neera; Gu, Mallikarjuna; Inturi, Swetha; White, Carl W.; Agarwal, Rajesh

2011-01-01

Bifunctional alkyalating agent, Sulfur mustard (SM)-caused cutaneous injury is characterized by inflammation and delayed blistering. Our recent studies demonstrated that 2-chloroethyl ethyl sulfide (CEES), a monofunctional analog of SM that can be used in laboratory settings, induces oxidative stress. This could be the major cause of the activation of Akt/MAP kinase and AP1/NF-κB pathways that are linked to the inflammation and microvesication, and histopathological alterations in SKH-1 hairless mouse skin. To further establish a link between CEES-induced DNA damage and signaling pathways and inflammatory responses, skin samples from mice exposed to 2 or 4 mg CEES for 9–48 h were subjected to molecular analysis. Our results show a strong CEES-induced phosphorylation of H2A.X and an increase in COX-2, iNOS, and MMP-9 levels, indicating the involvement of DNA damage and inflammation in CEES-caused skin injury in male and female mice. Since, our recent studies showed reduction in CEES-induced inflammatory responses by glutathione (GSH), we further assessed the role of oxidative stress in CEES-caused DNA damage and the induction of inflammatory molecules. Oral GSH (300mg/kg) administration 1 h before CEES exposure attenuated the increase in both CEES-induced H2A.X phosphorylation (59%) as well as expression of COX-2 (68%), iNOS (53%) and MMP-9 (54%). Collectively, our results indicate that CEES-induced skin injuries involve DNA damage and an induction of inflammatory mediators, at least in part via oxidative stress. This study could help in identifying countermeasures that alone or in combination, can target the unveiled pathways for reducing skin injuries in humans by SM. PMID:21722719

A prospective randomized trial comparing Foley catheter, oxytocin, and combination Foley catheter-oxytocin for labour induction with unfavourable cervix.

PubMed

El Khouly, Nabih I

2017-04-01

The purpose of this study was to evaluate the effectiveness and safety of transcervical Foley catheter with and without oxytocin versus oxytocin alone for labour induction with unfavourable cervix. This trial enrolled 108 women with singleton pregnancies presented for labour induction with unfavourable cervix. Patients were randomly assigned to receive Foley catheter alone (I), Foley catheter plus oxytocin (II) or oxytocin alone (III). Outcomes were analysed in terms of success of induction, induction delivery interval, route of delivery, dose and duration of oxytocin, and complications. Successful normal vaginal delivery was more common in group I (p = .02) compared to group III. Induction delivery time was statistically shorter in group II and group III (p < .001). Patients in group I required significantly less oxytocin dose and duration (p < .001). This led to our conclusion that induction of labour with Foley catheter without oxytocin increases success rate of normal vaginal delivery; however, it has a longer induction delivery interval with similar complications.

Effects of Low-dose Selenium on the Inflammatory Response in Coronary Artery Bypass Graft Surgery: A Clinical Trial

PubMed Central

Sedighinejad, Abbas; Imantalab, Vali; Mirmansouri, Ali; Mohammadzadeh Jouryabi, Ali; Kanani, Gholamreza; Nassiri Sheikhani, Nassir; Haghighi, Mohammad; Atrkarroushan, Zahra; Biazar, Gelareh

2016-01-01

Background Coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) triggers an inflammatory reaction, leading to the development of myocardial damage and dysfunction. It is suggested that selenium (Se), an essential trace element, has a protective role against oxidative stress. Decreased intraoperative Se levels might be an independent predictive factor for postoperative multiorgan failure. In spite of its proposed advantages, however, the optimal timing and dosage are not well known. Objectives To determine whether 600 µg of intravenous Se administration before induction of anesthesia for CABG surgery could attenuate inflammatory reactions in an Iranian population. Methods This randomized triple-blind clinical trial took place in the department of cardiac surgery of an academic hospital affiliated with Guilan University of Medical Sciences (GUMS) from May 2015 to September 2015. Eighty-eight eligible patients scheduled for elective on-pump CABG surgery were divided into two groups using randomized fixed quadripartite blocks. They received either an intravenous bolus of 600 µg Se before induction of anesthesia, or normal saline as a placebo. We had four measurement time-points: just before induction of anesthesia (T0), immediately after the end of CPB (T1), 24 hours after surgery (T2), and 48 hours after surgery (T3). Interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) serum levels were measured using the enzyme-linked immunosorbent assay (ELISA). Results Data from a total of 81 patients were analyzed: group S (n = 41) and group C (n = 40). There was no significant difference between the two groups with regard to baseline characteristics. In both groups, CPB caused markedly increased IL-6, TNF-α, and CRP plasma concentrations compared with baseline (P = 0.0001). However, the pattern of changes was not significantly different between group S (P = 0.068) and group C (P = 0.26). The IL-6 and TNF-α change trends were significant in each group (P=0.0001). However, comparing the two groups showed no significant difference. With regard to IL-6, there was no significant difference between the two groups at the time-points of T1 (P = 0.34), T2 (P = 0.17), and T3 (P = 0.056), and the same was found for TNF-α at T1 (P = 0.34), T2 (P = 0.17), and T3 (P = 0.056). With regard to CRP, the trend of the changes was significant in each group (P = 0.0001). However, comparing two groups showed a borderline significant difference between them at T1 (P = 0.039), but not at T2 (P = 0.075) or T3 (P = 0.11). Conclusions This study revealed that the administration of 600 μg of intravenous Se immediately before induction of anesthesia was safe, but when compared to a placebo, no predominant clinical effects or modifications in the systemic inflammatory response induced by on-pump CABG were observed. PMID:27795837

Circulating Current Suppressing Control’s Impact on Arm Inductance Selection for Modular Multilevel Converter

DOE PAGES

Li, Yalong; Jones, Edward A.; Wang, Fred

2016-10-13

Arm inductor in a modular multilevel converter (MMC) is used to limit the circulating current and dc short circuit fault current. The circulating current in MMC is dominated by second-order harmonic, which can be largely reduced with circulating current suppressing control. By analyzing the mechanism of the circulating current suppressing control, it is found that the circulating current at switching frequency becomes the main harmonic when suppression control is implemented. Unlike the second-order harmonic that circulates only within the three phases, switching frequency harmonic also flows through the dc side and may further cause high-frequency dc voltage harmonic. This articlemore » develops the theoretical relationship between the arm inductance and switching frequency circulating current, which can be used to guide the arm inductance selection. The experimental results with a downscaled MMC prototype verify the existence of the switching frequency circulating current and its relationship with arm inductance.« less

Kinetic Inductance Photodetectors Based on Nonequilibrium Response in Superconducting Thin-Film Structures

NASA Technical Reports Server (NTRS)

Sergeev, A. V.; Karasik, B. S.; Gogidze, I. G.; Mitin, V. V.

2001-01-01

While experimental studies of kinetic-inductance sensors have been limited so far by the temperature range near the superconducting transition, these detectors can be very sensitivity at temperatures well below the transition, where the number of equilibrium quasiparticles is exponentially small. In this regime, a shift of the quasiparticle chemical potential under radiation results in the change of the kinetic inductance, which can be measured by a sensitive SQUID readout. We modeled the kinetic inductance response of detectors made from disordered superconducting Nb, NbC, and MoRe films. Low phonon transparency of the interface between the superconductor and the substrate causes substantial re-trapping of phonons providing high quantum efficiency and the operating time of approximately 1 ms at 1 K. Due to the small number of quasiparticles, the noise equivalent power of the detector determined by the quasiparticle generation-recombination noise can be as small as approximately 10(exp -19) W/Hz(exp 1/2) at He4 temperatures.

Shortening the induction delivery interval with prostaglandins: a randomized controlled trial of solo or in combination

PubMed Central

Mahendru, Rajiv; Yadav, Shweta

2011-01-01

Objective To compare the efficacy and safety of misoprostol alone with dinoprostone followed by misoprostol, all inserted intravaginally in induction of labor at term and the obstetrical outcome. Material and Methods A pilot study comprising 111 primigravidae, >37 gestational weeks with singleton pregnancy in cephalic presentation having an unfavorable Bishop score admitted for labor induction, were considered and randomly allocated into two groups. In group I (n=55) with intravaginal 25mcg misoprostol 4 hourly (six doses at the most) and and group II (n=56), with dinoprostone 0.5mg followed eight hours later by 25mcg misoprostol induction to vaginal delivery time was found to be significantly different, being 14.8 h in group-I and shorter in group-II with a mean of 11.6 h. Vaginal delivery rates within 12 h (groups-I and −II: 47.2%, as compared to 60.7%, respectively) were found to be higher with dinoprostone-misoprostol induction, as well as vaginal delivery rates in 24 h, 80.0% and 91.1%. The need for oxytocin augmentation was more frequent in the misoprostol than in the dinoprostone-misoprostol group, (61.8%, and 39.3%), and all these observations were statistically significant. Abnormal foetal heart rate pattern occurred more frequently (18.2%) in group-I in contrast to 5.3% in group-II, as was the incidence rate of (18.2%) who had passage of meconium in group-I, this rate being significantly different from group-II having meconium passage in 3 cases, a rate of 5.3%. Conclusion Using dinoprostone followed by vaginal misoprostol is safe and effective for induction of labor with less need for oxytocin augmentation and shorter induction delivery interval. PMID:24591967

Clinical experience with induction therapy in renal transplantation.

PubMed

Muntean, Adriana; Lucan, Mihai; Barbos, Adrian; Elec, Alina; Iacob, Gheorghita; Loga, Luminita; Dican, Lucia

2013-01-01

Acute rejection (AR) is a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains the improvement seen in the results of transplantation in recent years. To assess the optimal immunosuppression regimen according to the immunological risk of renal transplant patients. We performed a retrospective study of 977 consecutive patients transplanted in our institution between January 2000 and December 2011. Recipients were classified according to the immunological risk (high, intermediate and low) and the type of induction therapy received. We evaluated the incidence of early acute rejection (eAR) and late acute rejection (lAR) and their influence on graft and patients survival in relation to the immunological risk and induction regimen used. The incidence of eAR was 5.4%, 6.4% and 1.4% in relation with the immunological risk, high, intermediate and low respectively. The most commonly used induction immunosuppression was rabbit antithymocyte globulin (ATG), followed by methylprednisolone and basiliximab. No statistical difference was found between the incidence of eAR according to the type of induction therapy and immunological risk. The graft survival was significantly better for the cases without eAR at 1 year (98.6% versus 94.4%, p=0.019), and 3 years (94.9% versus 88.9%, p=0.056). The patients survival was significantly better for those without eAR at 1 year after transplant (95.7% vs. 88.9%, p=0.051), 3 years (93.1% vs. 83.3%, p=0.008) and 5 years (92.2% vs. 79.6%, p=0.001). The incidence of lAR was between 0 and 7.1% according to the induction therapy, lacking any statistical significance (p=0.450). Tailoring the induction immunosuppression according to the immunological risk reduces the incidence of early acute rejection.

Clinical experience with induction therapy in renal transplantation

PubMed Central

MUNTEAN, ADRIANA; LUCAN, MIHAI; BARBOS, ADRIAN; ELEC, ALINA; IACOB, GHEORGHITA; LOGA, LUMINITA; DICAN, LUCIA

2013-01-01

Introduction Acute rejection (AR) is a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains the improvement seen in the results of transplantation in recent years. Objective To assess the optimal immunosuppression regimen according to the immunological risk of renal transplant patients. Method We performed a retrospective study of 977 consecutive patients transplanted in our institution between January 2000 and December 2011. Recipients were classified according to the immunological risk (high, intermediate and low) and the type of induction therapy received. We evaluated the incidence of early acute rejection (eAR) and late acute rejection (lAR) and their influence on graft and patients survival in relation to the immunological risk and induction regimen used. Results The incidence of eAR was 5.4%, 6.4% and 1.4% in relation with the immunological risk, high, intermediate and low respectively. The most commonly used induction immunosuppression was rabbit antithymocyte globulin (ATG), followed by methylprednisolone and basiliximab. No statistical difference was found between the incidence of eAR according to the type of induction therapy and immunological risk. The graft survival was significantly better for the cases without eAR at 1 year (98.6% versus 94.4%, p=0.019), and 3 years (94.9% versus 88.9%, p=0.056). The patients survival was significantly better for those without eAR at 1 year after transplant (95.7% vs. 88.9%, p=0.051), 3 years (93.1% vs. 83.3%, p=0.008) and 5 years (92.2% vs. 79.6%, p=0.001). The incidence of lAR was between 0 and 7.1% according to the induction therapy, lacking any statistical significance (p=0.450). Conclusion Tailoring the induction immunosuppression according to the immunological risk reduces the incidence of early acute rejection. PMID:26527980

Effect of Home Cage Bedding in the Induction Chamber on Serum Cortisol and Corticosterone Levels in Response to Isoflurane-induced Anesthesia in C57BL/6J Mice.

PubMed

Reiter, Cara P; Christy, Amanda C; Olsen, Cara H; Bentzel, David E

2017-03-01

Mice are routinely anesthetized with isoflurane in an induction chamber. The AVMA Guidelines for the Euthanasia of Animals states that distress should be minimized during euthanasia but does not address this point in regard to induction of anesthesia. Here we evaluated the potential for familiar surroundings to reduce the adrenocortical response of mice during anesthesia induction with isoflurane. However, adding bedding from the animals' home cage to the induction chamber failed to significantly reduce serum cortisol or corticosterone levels in male and female C57BL/6J mice. These results indicate that familiar surroundings do not appear sufficient to reduce the adrenocortical response of mice during anesthesia induction with isoflurane.

Effect of Home Cage Bedding in the Induction Chamber on Serum Cortisol and Corticosterone Levels in Response to Isoflurane-induced Anesthesia in C57BL/6J Mice

PubMed Central

Reiter, Cara P; Christy, Amanda C; Olsen, Cara H; Bentzel, David E

2017-01-01

Mice are routinely anesthetized with isoflurane in an induction chamber. The AVMA Guidelines for the Euthanasia of Animals states that distress should be minimized during euthanasia but does not address this point in regard to induction of anesthesia. Here we evaluated the potential for familiar surroundings to reduce the adrenocortical response of mice during anesthesia induction with isoflurane. However, adding bedding from the animals’ home cage to the induction chamber failed to significantly reduce serum cortisol or corticosterone levels in male and female C57BL/6J mice. These results indicate that familiar surroundings do not appear sufficient to reduce the adrenocortical response of mice during anesthesia induction with isoflurane. PMID:28315639

Transcriptional analysis of different stress response genes in Escherichia coli strains subjected to sodium chloride and lactic acid stress.

PubMed

Peng, Silvio; Stephan, Roger; Hummerjohann, Jörg; Tasara, Taurai

2014-12-01

Survival of Escherichia coli in food depends on its ability to adapt against encountered stress typically involving induction of stress response genes. In this study, the transcriptional induction of selected acid (cadA, speF) and salt (kdpA, proP, proW, otsA, betA) stress response genes was investigated among five E. coli strains, including three Shiga toxin-producing strains, exposed to sodium chloride or lactic acid stress. Transcriptional induction upon lactic acid stress exposure was similar in all but one E. coli strain, which lacked the lysine decarboxylase gene cadA. In response to sodium chloride stress exposure, proW and otsA were similarly induced, while significant differences were observed between the E. coli strains in induction of kdpA, proP and betA. The kdpA and betA genes were significantly induced in four and three strains, respectively, whereas one strain did not induce these genes. The proP gene was only induced in two E. coli strains. Interestingly, transcriptional induction differences in response to sodium chloride stress exposure were associated with survival phenotypes observed for the E. coli strains in cheese as the E. coli strain lacking significant induction in three salt stress response genes investigated also survived poorly compared to the other E. coli strains in cheese. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Agrobacterium and Tumor Induction: A Model System.

ERIC Educational Resources Information Center

Lennox, John E.

1980-01-01

The author offers laboratory procedures for experiments using the bacterium, Agrobacterium tumefaciens, which causes crown gall disease in a large number of plants. Three different approaches to growing a culture are given. (SA)

Toxicity of aerosol propellants in the respiratory and circulatory systems. VII. Influence of pulmonary emphysema and anesthesia in the rat.

PubMed

Watanabe, T; Aviado, D M

1975-01-01

Experimental induction of pulmonary emphysema caused an increase in sensitivity of the rat to toxicity from inhalation of propellants. The emphysematous rat showed an exaggerated reduction in pulmonary compliance in response to inhalation of trichlorofluoromethane (FC 11). In emphysematous and non emphysematous rats without anesthesia the inhalation of FC 11 caused tachycardia, arrhythmias and other abnormalities in the electrocardiogram. The tachycardiac response was eliminated by induction of barbiturate anesthesia, which increased the sensitivity of the heart to occurrence of abnormalities in the electrocardiogram in response to inhalation of FC 11 as well as of dichlorodifluoromethane (FC 12) and difluoroethane (FC 152a). The acceleration in heart rate in response to inhalation of FC 11, hypoxia or hypercapnea was prevented by prior treatment with a beta-blocking drug.

Emittance Growth in the DARHT-II Linear Induction Accelerator

DOE PAGES

Ekdahl, Carl; Carlson, Carl A.; Frayer, Daniel K.; ...

2017-10-03

The dual-axis radiographic hydrodynamic test (DARHT) facility uses bremsstrahlung radiation source spots produced by the focused electron beams from two linear induction accelerators (LIAs) to radiograph large hydrodynamic experiments driven by high explosives. Radiographic resolution is determined by the size of the source spot, and beam emittance is the ultimate limitation to spot size. On the DARHT-II LIA, we measure an emittance higher than predicted by theoretical simulations, and even though this accelerator produces submillimeter source spots, we are exploring ways to improve the emittance. Some of the possible causes for the discrepancy have been investigated using particle-in-cell codes. Finally,more » the simulations establish that the most likely source of emittance growth is a mismatch of the beam to the magnetic transport, which can cause beam halo.« less

Emittance Growth in the DARHT-II Linear Induction Accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ekdahl, Carl; Carlson, Carl A.; Frayer, Daniel K.

The dual-axis radiographic hydrodynamic test (DARHT) facility uses bremsstrahlung radiation source spots produced by the focused electron beams from two linear induction accelerators (LIAs) to radiograph large hydrodynamic experiments driven by high explosives. Radiographic resolution is determined by the size of the source spot, and beam emittance is the ultimate limitation to spot size. On the DARHT-II LIA, we measure an emittance higher than predicted by theoretical simulations, and even though this accelerator produces submillimeter source spots, we are exploring ways to improve the emittance. Some of the possible causes for the discrepancy have been investigated using particle-in-cell codes. Finally,more » the simulations establish that the most likely source of emittance growth is a mismatch of the beam to the magnetic transport, which can cause beam halo.« less

Role of Lipid Peroxidation-Derived α, β-Unsaturated Aldehydes in Vascular Dysfunction

PubMed Central

Lee, Seung Eun; Park, Yong Seek

2013-01-01

Vascular diseases are the most prominent cause of death, and inflammation and vascular dysfunction are key initiators of the pathophysiology of vascular disease. Lipid peroxidation products, such as acrolein and other α, β-unsaturated aldehydes, have been implicated as mediators of inflammation and vascular dysfunction. α, β-Unsaturated aldehydes are toxic because of their high reactivity with nucleophiles and their ability to form protein and DNA adducts without prior metabolic activation. This strong reactivity leads to electrophilic stress that disrupts normal cellular function. Furthermore, α, β-unsaturated aldehydes are reported to cause endothelial dysfunction by induction of oxidative stress, redox-sensitive mechanisms, and inflammatory changes such as induction of cyclooxygenase-2 and cytokines. This review provides an overview of the effects of lipid peroxidation products, α, β-unsaturated aldehydes, on inflammation and vascular dysfunction. PMID:23819013

ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish

PubMed Central

Ishikawa, Tokiro; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Todo, Takeshi; Kamei, Yasuhiro; Shigenobu, Shuji; Tanaka, Minoru; Saito, Taro L.; Yoshimura, Jun; Morishita, Shinichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Taniguchi, Yoshihito; Takeda, Shunichi; Mori, Kazutoshi

2013-01-01

ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra. PMID:23447699

ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish.

PubMed

Ishikawa, Tokiro; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Todo, Takeshi; Kamei, Yasuhiro; Shigenobu, Shuji; Tanaka, Minoru; Saito, Taro L; Yoshimura, Jun; Morishita, Shinichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Taniguchi, Yoshihito; Takeda, Shunichi; Mori, Kazutoshi

2013-05-01

ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra.

Exploring environmental causes of altered ras effects: fragmentation plus integration?

PubMed

Porta, Miquel; Ayude, Daniel; Alguacil, Juan; Jariod, Manuel

2003-02-01

Mutations in ras genes are the most common abnormality of oncogenes in human cancer and a major example of activation by point mutation. Experimental and epidemiological studies support the notion that Ki-ras activation and expression may be chemically related. We discuss the potential role of several environmental compounds in the induction or promotion of ras mutations in humans, with a focus on exocrine pancreatic cancer, the human tumor with the highest prevalence at diagnosis of Ki-ras mutations. Organochlorine compounds, organic solvents, and coffee compounds may play an indirect role in causing Ki-ras mutations, rather than as direct inducers of the mutations. Although for some organochlorine compounds the induction of point mutations in ras oncogenes cannot be excluded, it seems more likely that the effects of these compounds are mediated through nongenomic or indirectly genotoxic mechanisms of action. Organic solvents also may act via enzymatic induction of ras mutagens or by providing a proliferation advantage to ras-mutated cell clones. In exocrine pancreatic cancer, caffeine, other coffee compounds, or other factors with which coffee drinking is associated could modulate Ki-ras activation by interfering with DNA repair, cell-cycle checkpoints, and apoptosis. Asbestos, cigarette smoking, and some dietary factors also may be involved in the initiation or the promotion of Ki-ras mutations in lung and colon cancers. Further development of the mechanistic scenarios proposed here could contribute to a meaningful integration of biological, clinical, and environmental knowledge on the causes of altered ras effects. Copyright 2003 Wiley-Liss, Inc.

Induction of Podocyte-Derived VEGF Ameliorates Podocyte Injury and Subsequent Abnormal Glomerular Development Caused by Puromycin Aminonucleoside

PubMed Central

Ma, Ji; Matsusaka, Taiji; Yang, Hai-Chun; Zhong, Jianyong; Takagi, Nobuaki; Fogo, Agnes B.; Kon, Valentina; Ichikawa, Iekuni

2011-01-01

Our previous studies using puromycin aminonucleoside (PAN) established that podocyte damage leads to glomerular growth arrest during development and glomerulosclerosis later in life. The present study examined the potential benefit of maintaining podocyte-derived vascular endothelial growth factor (VEGF) in podocyte defense and survival following PAN injury using conditional transgenic podocytes and mice, in which human VEGF-A (hVEGF) transgene expression is controlled by tetracycline responsive element (TRE) promoter and reverse tetracycline transactivator (rtTA) in podocytes. In vitro experiments used primary cultured podocytes harvested from mice carrying podocin-rtTA and TRE-hVEGF transgenes, in which hVEGF can be induced selectively. Induction of VEGF in PAN-exposed podocytes resulted in preservation of intrinsic VEGF, α-actinin-4 and synaptopodin, anti-apoptotic marker Bcl-xL/Bax, as well as attenuation in apoptotic marker cleaved/total caspase-3. In vivo, compared with genotype controls, PAN-sensitive neonatal mice with physiologically relevant levels of podocyte-derived VEGF showed significantly larger glomeruli. Further, PAN-induced up-regulation of desmin, down-regulation of synaptopodin and nephrin, and disruption of glomerular morphology was significantly attenuated in VEGF-induced transgenic mice. Our data indicate that podocyte-derived VEGF provides self-preservation functions, which can rescue the cell following injury and preempt subsequent deterioration of the glomerulus in developing mice. PMID:21451433

Carbon tetrachloride-induced hepatotoxicity and its amelioration by Agaricus blazei Murrill extract in a mouse model.

PubMed

Chang, Jin-Biou; Wu, Ming-Fang; Yang, Yi-Yuan; Leu, Sy-Jye; Chen, Yung-Liang; Yu, Chun-Shu; Yu, Chieh-Chih; Chang, Shu-Jen; Lu, Hsu-Feng; Chung, Jing-Gung

2011-01-01

This study was conducted to evaluate the hepatoprotective effect of Agaricus blazei Murrill extract (ABM) against experimentally induced carbon tetrachloride (CCl(4)) toxicity in male BALB/c mice. The experiments included a normal group (no induction by CCl(4)), CCl(4-)induction group (with hepatotoxicity by CCl(4) and without treatment) and experimental groups with low dose (200 mg) or high dose (2,000 mg) of ABM extract (per kilogram mouse weight). All groups other than the normal group were treated with intraperitoneal injections of CCl(4) twice a week. Mice were tube-fed with experimental ABM extracts or double-distilled water, accordingly, on the remaining four days each week. The whole experimental protocol lasted 8 weeks; blood and liver samples were collected for biochemical and tissue histochemical analysis. Only administration of a high dose of ABM to treatment groups resulted in a significant abrogation of CCL(4)-induced increase of serum aspartate aminotransferase (AST) and alanine transaminase (ALT). Post-treatment with ABM also did not significantly reverse the alterations of glutathione peroxidase (GSHPx) and catalase. Both high- and low-dose ABM treatment reduced hepatic necrosis and fibrosis caused by CCl(4) in comparison with the CCl(4) control group in the histochemical analyses. Our results suggest that the ABM extract affects the levels of ALT and AST in mice.

Determination of changes in the concentration and distribution of elements within olive drupes (cv. Leccino) from Se biofortified plants, using laser ablation inductively coupled plasma mass spectrometry.

PubMed

D'Amato, Roberto; Petrelli, Maurizio; Proietti, Primo; Onofri, Andrea; Regni, Luca; Perugini, Diego; Businelli, Daniela

2018-03-25

Biofortification of food crops has been used to increase the intake of Se in the human diet, even though this may change the concentration of other elements and modify the nutritional properties of the enriched food. Selenium biofortification programs should include routine assessment of the overall mineral composition of enriched plants. Laser ablation inductively coupled plasma mass spectrometry (LA ICP-MS) was used for the assessment of mineral composition of table olives. Olive trees were fertilized with sodium selenate before flowering. At harvest, the edible parts of drupes proved to be significantly enriched in Se, delivering 6.1 μg g -1 (39% of the RDA for five olives). Such enrichment was followed by significant changes in the concentrations of B, Mg, K, Cr, Mn, Fe and Cu in edible parts, which are discussed for their impact on food quality. The biofortification of olive plants has allowed the enrichment of fruits with selenium. Enrichment with selenium has caused an increase in the concentration of other elements, which can change the nutritional quality of the drupes. The analytical technique used well as a valuable tool for routinely determining the chemical composition of all fruit parts. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Induction of Broad-Spectrum Protective Immunity against Disparate Cryptococcus Serotypes

PubMed Central

Van Dyke, Marley C. Caballero; Chaturvedi, Ashok K.; Hardison, Sarah E.; Leopold Wager, Chrissy M.; Castro-Lopez, Natalia; Hole, Camaron R.; Wozniak, Karen L.; Wormley, Floyd L.

2017-01-01

Cryptococcosis is a fungal disease caused by multiple Cryptococcus serotypes; particularly C. neoformans (serotypes A and D) and C. gattii (serotypes B and C). To date, there is no clinically available vaccine to prevent cryptococcosis. Mice given an experimental pulmonary vaccination with a C. neoformans serotype A strain engineered to produce interferon-γ, denoted H99γ, are protected against a subsequent otherwise lethal experimental infection with C. neoformans serotype A. Thus, we determined the efficacy of immunization with C. neoformans strain H99γ to elicit broad-spectrum protection in BALB/c mice against multiple disparate Cryptococcus serotypes. We observed significantly increased survival rates and significantly decreased pulmonary fungal burden in H99γ immunized mice challenged with Cryptococcus serotypes A, B, or D compared to heat-killed H99γ (HKH99γ) immunized mice. Results indicated that prolonged protection against Cryptococcus serotypes B or D in H99γ immunized mice was CD4+ T cell dependent and associated with the induction of predominantly Th1-type cytokine responses. Interestingly, immunization with H99γ did not elicit greater protection against challenge with the Cryptococcus serotype C tested either due to low overall virulence of this strain or enhanced capacity of this strain to evade host immunity. Altogether, these studies provide “proof-of-concept” for the development of a cryptococcal vaccine that provides cross-protection against multiple disparate serotypes of Cryptococcus. PMID:29163469

Alcohol and acute pancreatitis. An experimental study in the rat.

PubMed

Jalovaara, P; Apaja, M

1978-01-01

The effect of chronic alcohol pretreatment and various pancreatobiliary secretions on the severity of experimental pancreatitis was studied in the rat. 95 rats were pretreated with ethanol (20% w/v, 1.1 ml/100 g body weight) five times weekly for 10 to 12 weeks by gastric intubation. 88 rats served as controls. Pancreatic lesions were produced by retograde injection of different pancreatobiliary secretions into the pancreatic ducts. The secretions were collected from both normal and chronically alcohol-fed rats, and each was used for induction of experimental pancreatitis in the control and alcohol pretreated rats. Bile obtained from normal rats was no more toxic to the pancreas than 0.9% saline solution, while bile obtained from the chronically alcohol-fed rats caused significantly more serious lesions to the pancreas than did normal rat bile. Bile-pancreatic juice (mixture of secretions at papilla of Vater) of normal and chronically alcohol-fed rats was as toxic as the bile of the alcohol-fed rats. Alcohol pretreatment had no significant effect on the severity of pancreatitis when control and alcohol-fed groups separately or the whole material according to pretreatment was examined. These results suggest that the metabolic effects of ethanol on the pancreas as such do not sensitize the pancreas to acute pancreatitis. An exogenous mechanism is required. The reflux of toxic alcoholic bile into the pancreas might act as an induction factor in acute alcohol pancreatitis.

Safety Assessment of Commonly Used Nanoparticles in Biomedical Applications: Impact on Inflammatory Processes

NASA Astrophysics Data System (ADS)

Alnasser, Yossef

Nanotechnology offers great promise in the biomedical field. Current knowledge of nanoparticles' (NPs) safety and possible mechanisms of various particle types' toxicity is insufficient. The role of particle properties and the route of particles administration in toxic reactions remain unexplored. In this thesis, we aimed to inspect the interrelationship between particle size, chemical composition and toxicological effects of four candidate NPs for drug delivery systems: gold (Au), chitosan, silica, and poly (lactide-co-glycolide) (PLGA). Mice model was combined with in vitro study to explore NPs' safety. We investigated mice survival, weight, behavior, and pro-inflammatory changes. NF-kappaB induction was assessed in vitro using the Luciferase Assay System. As observed in mice, Au NPs had a higher toxicity profile at a shorter duration than the other NPs. This was significantly in concordance with pro-inflammatory changes which may be the key routes of Au NPs toxicity. Although silica NPs induced NF-kappaB, they were less toxic to the mice than Au NPs and did not lead to the pro-inflammatory changes. Chitosan NPs were toxic to the mice but failed to cause significant NF-kappaB induction and pro-inflammatory changes. These findings indicate that chitosan NPs might not have the same pathophysiologic mechanism as the Au NPs. Comparative analysis in this model demonstrated that PLGA NPs is the safest drug delivery candidate to be administered subcutaneously.

Special considerations--Induction of labor in low-resource settings.

PubMed

Smid, Marcela; Ahmed, Yusuf; Ivester, Thomas

2015-10-01

Induction of labor in resource-limited settings has the potential to significantly improve health outcomes for both mothers and infants. However, there are relatively little context-specific data to guide practice, and few specific guidelines. Also, there may be considerable issues regarding the facilities and organizational capacities necessary to support safe practices in many aspects of obstetrical practice, and for induction of labor in particular. Herein we describe the various opportunities as well as challenges presented by induction of labor in these settings. Copyright © 2015 Elsevier Inc. All rights reserved.

Multicenter phase II study of weekly docetaxel, cisplatin, and S-1 (TPS) induction chemotherapy for locally advanced squamous cell cancer of the head and neck.

PubMed

Bae, Woo Kyun; Hwang, Jun Eul; Shim, Hyun Jeong; Cho, Sang Hee; Lee, Ki Hyeong; Han, Hye Suk; Song, Eun-Kee; Yun, Hwan Jung; Cho, In Sung; Lee, Joon Kyoo; Lim, Sang-Chul; Chung, Woong-Ki; Chung, Ik-Joo

2013-03-06

The purpose of this study was to evaluate the efficacy and tolerability of weekly docetaxel, cisplatin, and S-1 (weekly TPS) as induction chemotherapy for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). A total of 35 patients with previously untreated, locally advanced HNSCC were enrolled. Seven patients (20%) were diagnosed with stage III HNSCC and 28 patients (80%) were diagnosed with stage IV. Induction treatment included 30 mg/m(2) docetaxel on day 1 and 8, 60 mg/m(2) cisplatin on day 1, and 70 mg/m(2) S-1 on days 1 to 14. The regimen was repeated every 21 days. After three courses of induction chemotherapy, patients received concurrent chemoradiotherapy. Among the 35 patients, 30 (85.7%) completed induction chemotherapy. The response to induction chemotherapy was as follows: nine patients (25.7%) achieved a complete response (CR) and the overall response rate (ORR) was 85.7%. Grades 3-4 toxicity during induction therapy included neutropenia (28.5%), neutropenic fever (8.5%), and diarrhea (17.1%). After completion of concurrent chemoradiotherapy, the CR rate was 62.8% and the partial response (PR) was 22.8%. Estimates of progression-free and overall survival at 2 years were 73.2% and 79.3%, respectively. Weekly TPS is a promising regimen that is well-tolerated, causes minimal myelosuppression and is effective as an outpatient regimen for locally advanced HNSCC. ClinicalTrials.gov: NCT01645748.

Attenuated microglial activation mediates tolerance to the neurotoxic effects of methamphetamine.

PubMed

Thomas, David M; Kuhn, Donald M

2005-02-01

Methamphetamine causes persistent damage to dopamine nerve endings of the striatum. Repeated, intermittent treatment of mice with low doses of methamphetamine leads to the development of tolerance to its neurotoxic effects. The mechanisms underlying tolerance are not understood but clearly involve more than alterations in drug bioavailability or reductions in the hyperthermia caused by methamphetamine. Microglia have been implicated recently as mediators of methamphetamine-induced neurotoxicity. The purpose of the present studies was to determine if a tolerance regimen of methamphetamine would attenuate the microglial response to a neurotoxic challenge. Mice treated with a low-dose methamphetamine tolerance regimen showed minor reductions in striatal dopamine content and low levels of microglial activation. When the tolerance regimen preceded a neurotoxic challenge of methamphetamine, the depletion of dopamine normally seen was significantly attenuated. The microglial activation that occurs after a toxic methamphetamine challenge was blunted likewise. Despite the induction of tolerance against drug-induced toxicity and microglial activation, a neurotoxic challenge with methamphetamine still caused hyperthermia. These results suggest that tolerance to methamphetamine neurotoxicity is associated with attenuated microglial activation and they further dissociate its neurotoxicity from drug-induced hyperthermia.

Ovulation induction in women with polycystic ovary syndrome: an update.

PubMed

Bhagavath, Balasubramanian; Carson, Sandra A

2012-03-01

Infertility is frequently caused by anovulation. The affected women present with irregular menstrual cycles and the most common diagnosis is polycystic ovary syndrome. Ovulation induction is commonly used to treat these women. Clomiphene citrate (a selective estrogen receptor modulator or SERM) remains the most used medication for treating this condition. Alternatives that have been used include other SERMs such as tamoxifen, aromatase inhibitors, insulin sensitizing agents, and ovarian drilling. Evidence for and against the effectiveness of these agents has fluctuated over the last decade. Controversies surrounding the use of ovulation induction such as development of functional cysts, high-order multiple births, and development of ovarian cancer have been further studied and some controversies have almost been laid to rest in the last decade. Copyright © 2012 Mosby, Inc. All rights reserved.

Rapacuronium and the risk of bronchospasm in pediatric patients.

PubMed

Rajchert, Donna M; Pasquariello, Caroline A; Watcha, Mehernoor F; Schreiner, Mark S

2002-03-01

We conducted this study to determine the risk factors for the development of bronchospasm after the administration of rapacuronium and to determine if children with bronchospasm on induction of anesthesia were more likely to have received rapacuronium compared with other muscle relaxants. In a retrospective cohort study, all anesthetic records in which rapacuronium was administered were reviewed to determine which patients developed bronchospasm during induction of anesthesia. Two-hundred-eighty-seven patients were identified, of whom 12 (4.2%; 95% confidence interval [CI], 2.2%--7.2%) developed bronchospasm during induction of anesthesia. Significant risk factors for the development of bronchospasm with administration of rapacuronium included rapid sequence induction (relative risk [RR], 17.9; 95% CI, 2.9--infinity) and prior history of reactive airways disease (RR, 4.6; 95% CI, 1.5--14.3). In a case-control study, all cases of bronchospasm during induction of anesthesia in the 5-mo time period that rapacuronium was available for clinical use were identified. Aside from the 12 cases of bronchospasm with rapacuronium, 11 additional cases of bronchospasm were associated with the use of other muscle relaxants. Four controls were randomly selected for each of the 23 cases of bronchospasm. Children with bronchospasm during induction of anesthesia were several times more likely (odds ratio, 10.1; 95% CI, 3.5--28.8) for having received rapacuronium compared with other muscle relaxants. In a retrospective cohort study, significant risk factors for the development of bronchospasm with the administration of rapacuronium on induction of anesthesia included rapid sequence induction and prior history of reactive airways disease. In a case-control study, children with bronchospasm during induction of anesthesia were several times more likely to have received rapacuronium compared with other muscle relaxants.

Women's perceptions, expectations and satisfaction with induced labour--a questionnaire-based study.

PubMed

Shetty, Ashalatha; Burt, Rhona; Rice, Pat; Templeton, Allan

2005-11-01

To evaluate the understanding and expectations of women undergoing labour induction, to assess their actual experience of the process and to compare their satisfaction with labour to those labouring spontaneously. Four hundred and fifty women at term undergoing induction of labour and cervical ripening with prostaglandinE2 vaginal tablets and 450 women labouring spontaneously were recruited into the study. The induction group were requested to complete a questionnaire prior to the start of their induction process and another questionnaire post-delivery. The post-delivery questionnaire contained two sections, one pertaining to issues to do with the induction and the second with the actual labour process. The spontaneously labouring group was requested to complete a questionnaire post-delivery, which only contained the section pertaining to the actual labour process. The main outcome measures were satisfaction with labour, perception of pain and length of labour between the induced and spontaneous labour groups, and issues that the women might wish changed about their induction. In the induction group, 34.7% were not satisfied with the information they received about the induction prior to the procedure and 27.2% expected to deliver within 12h of the administration of the inducing agent. Post-induction, 40% of the women felt the most important aspect they would like to change about their induction were they to have another one, would be the speed of the induction, 13.6% felt they might wish to take the inducing agent orally, 7% to have fewer vaginal examinations and 9% to have fewer complications. Among the women who returned questionnaires, 26.3% had a caesarean delivery in the induction group and 21.4% in the spontaneous labour group. Significantly more women were satisfied with their labour in the spontaneous labour group 79.5% versus 70.4%, RR 0.89, 95% CI 0.8-0.96, P=0.006). Labour that is artificially induced does result in lower satisfaction rates as compared to that following spontaneous onset. The longer time delay between the start of the induction and the delivery plays a significant part in this, with the mode of administration of the inducing agent, more vaginal examinations and the increase in caesarean deliveries being perceived as secondary issues. There is a need to improve the information provided to women undergoing labour induction, to counter unrealistic expectations and thereby improve satisfaction.

The Hog1 Mitogen-Activated Protein Kinase Mediates a Hypoxic Response in Saccharomyces cerevisiae

PubMed Central

Hickman, Mark J.; Spatt, Dan; Winston, Fred

2011-01-01

We have studied hypoxic induction of transcription by studying the seripauperin (PAU) genes of Saccharomyces cerevisiae. Previous studies showed that PAU induction requires the depletion of heme and is dependent upon the transcription factor Upc2. We have now identified additional factors required for PAU induction during hypoxia, including Hog1, a mitogen-activated protein kinase (MAPK) whose signaling pathway originates at the membrane. Our results have led to a model in which heme and ergosterol depletion alters membrane fluidity, thereby activating Hog1 for hypoxic induction. Hypoxic activation of Hog1 is distinct from its previously characterized response to osmotic stress, as the two conditions cause different transcriptional consequences. Furthermore, Hog1-dependent hypoxic activation is independent of the S. cerevisiae general stress response. In addition to Hog1, specific components of the SAGA coactivator complex, including Spt20 and Sgf73, are also required for PAU induction. Interestingly, the mammalian ortholog of Spt20, p38IP, has been previously shown to interact with the mammalian ortholog of Hog1, p38. Taken together, our results have uncovered a previously unknown hypoxic-response pathway that may be conserved throughout eukaryotes. PMID:21467572

Hepatitis B virus X protein suppresses virus-triggered IRF3 activation and IFN-beta induction by disrupting the VISA-associated complex.

PubMed

Wang, Xianmiao; Li, Ying; Mao, Aiping; Li, Chao; Li, Yongkui; Tien, Po

2010-09-01

Viral RNAs produced during viral infection are recognized by the cytoplasmic RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). A central adapter protein downstream of RIG-I and MDA5 is the mitochondrial membrane protein virus-induced signaling adaptor (VISA), which mediates the induction of type I interferons (IFNs) through the activation of transcription factors such as nuclear factor-kappaB (NF-kappaB) and IFN-regulatory factor-3 (IRF3). Here we found that hepatitis B virus (HBV)-encoded X protein (HBx) acts as an inhibitor of virus-triggered IRF3 activation and IFN-beta induction. Reporter and plaque assays indicate that HBx inhibits signaling by components upstream but not downstream of VISA. Immunoprecipitation experiments indicate that HBx interacts with VISA and disrupts the association of VISA with its upstream and downstream components. These findings suggest that HBx acts as a suppressor of virus-triggered induction of type I IFNs, which explains the observation that HBV causes transient and chronic infection in hepatocytes but fails to activate the pattern recognition receptor-mediated IFN induction pathways.

Bax and Bak are required for apoptosis induction by sulforaphane, a cruciferous vegetable-derived cancer chemopreventive agent.

PubMed

Choi, Sunga; Singh, Shivendra V

2005-03-01

Sulforaphane, a constituent of many edible cruciferous vegetables, including broccoli, effectively suppresses proliferation of cancer cells in culture and in vivo by causing apoptosis induction, but the sequence of events leading to cell death is poorly defined. Here, we show that multidomain proapoptotic Bcl-2 family members Bax and Bak play a critical role in apoptosis induction by sulforaphane. This conclusion is based on the following observations: (a) sulforaphane treatment caused a dose- and time-dependent increase in the protein levels of both Bax and Bak and conformational change and mitochondrial translocation of Bax in SV40-transformed mouse embryonic fibroblasts (MEF) derived from wild-type mice to trigger cytosolic release of apoptogenic molecules (cytochrome c and Smac/DIABLO), activation of caspase-9 and caspase-3, and ultimately cell death; (b) MEFs derived from Bax or Bak knockout mice resisted cell death by sulforaphane, and (c) MEFs derived from Bax and Bak double knockout mice exhibited even greater protection against sulforaphane-induced cytochrome c release, caspase activation, and apoptosis compared with wild-type or single knockout cells. Interestingly, sulforaphane treatment also caused a dose- and time-dependent increase in the protein level of Apaf-1 in wild-type, Bax-/-, and Bak-/- MEFs but not in double knockout, suggesting that Bax and Bak might regulate sulforaphane-mediated induction of Apaf-1 protein. A marked decline in the protein level of X-linked inhibitor of apoptosis on treatment with sulforaphane was also observed. Thus, it is reasonable to postulate that sulforaphane-induced apoptosis is amplified by a decrease in X-linked inhibitor of apoptosis level, which functions to block cell death by inhibiting activities of caspases. In conclusion, the results of the present study indicate that Bax and Bak proteins play a critical role in initiation of cell death by sulforaphane.

Mechanisms for Hepatobiliary Toxicity in Rats Treated with an Antagonist of Melanin Concentrating Hormone Receptor 1 (MCHR1).

PubMed

Otieno, Monicah A; Bhaskaran, Vasanthi; Janovitz, Evan; Callejas, Yimer; Foster, William B; Washburn, William; Megill, John R; Lehman-McKeeman, Lois; Gemzik, Brian

2017-02-01

The objective of this work was to investigate the mechanisms of hepatobiliary toxicity caused by thienopyrimidone MCHR1 antagonists using BMS-773174 as a tool molecule. Co-administration of the pan CYP inhibitor 1-aminobenzotriazole with BMS-773174 prevented hepatobiliary damage, and direct delivery of the diol metabolite BMS-769750 caused hepatobiliary toxicity, identifying the diol and possibly its downstream hydroxyacid (BMS-800754) metabolite as the toxic species. Rat liver gene expression revealed treatment-related changes in hepatic transporters and induction of oval cell-specific genes including deleted malignant tumor 1 (Dmbt1). The metabolites did not alter hepatic transporter activities, suggesting that transporter-mediated cholestasis was not involved. Because injury to biliary epithelium can result in adaptive hyperplasia, rat biliary epithelial cells (BECs) were isolated and exposed to the oxidative metabolites. BMS-769750 was cytotoxic to BECs, but not rat hepatocytes, suggesting a role of the diol in biliary epithelial injury. BMS-800754 was cytotoxic to rat hepatocytes therefore its contribution to hepatocyte injury in rats is a possibility. Induction of Dmbt1 in rat BECs was investigated because of its role in hepatic progenitor cell differentiation/proliferation during injury. Dmbt1 mRNA was induced by BMS-769750, but not BMS-800754 in BECs; this induction and cellular injury was confirmed with diol metabolites formed by other compounds with the same hepatobiliary liability. In conclusion, hepatobiliary injury by thienopyrimidinone MCHR1 antagonists was driven through a CYP-mediated bioactivation pathway. Induction of Dmbt1 mRNA coupled with cellular injury suggests that injury of biliary epithelium may be the first step toward an adaptive proliferative response causing BDH by these compounds. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Sustained neuroprotection from a single intravitreal injection of PGJ₂ in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy.

PubMed

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M; Bernstein, Steven L

2014-10-08

Prostaglandin J₂ (PGJ₂) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ₂ in a nonhuman primate model of NAION (pNAION). We assessed PGJ₂ toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ₂ or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ₂ or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. PGJ₂ caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ₂ used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ₂; however, the amplitudes returned to normal in all animals within 1 week. In all eyes, a single IVT dose of PGJ₂ administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). In nonhuman primates, PGJ₂ administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ₂ is neuroprotective when administered up to 5 hours after induction of pNAION. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment

PubMed Central

2011-01-01

Background Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline. Methods Three independent cohorts of adult (12-13 months) and aged (26-28 months) F344xBN rats were behaviorally characterized by Morris water maze testing. Expression of MHC II pathway-associated genes identified by transcriptomic analysis as upregulated with advanced aging was quantified by qPCR in synaptosomal fractions derived from whole hippocampus and in hippocampal subregion dissections (CA1, CA3, and DG). Activation of astrocytes and microglia was assessed by GFAP and Iba1 protein expression, and by immunohistochemical visualization of GFAP and both CD74 (Ox6) and Iba1. Results We report a marked age-related induction of neuroinflammatory signaling transcripts (i.e., MHC II components, toll-like receptors, complement, and downstream signaling factors) throughout the hippocampus in all aged rats regardless of cognitive status. Astrocyte and microglial activation was evident in CA1, CA3 and DG of intact and impaired aged rat groups, in the absence of differences in total numbers of GFAP+ astrocytes or Iba1+ microglia. Both mild and moderate microglial activation was significantly increased in all three hippocampal subregions in aged cognitively intact and cognitively impaired rats compared to adults. Neither induction of MHCII pathway gene expression nor glial activation correlated to cognitive performance. Conclusions These data demonstrate a novel, coordinated age-related induction of the MHC II immune response pathway and glial activation in the hippocampus, indicating an allostatic shift toward a para-inflammatory phenotype with advancing age. Our findings demonstrate that age-related induction of these aspects of hippocampal neuroinflammation, while a potential contributing factor, is not sufficient by itself to elicit impairment of spatial learning and memory in models of normative aging. Future efforts are needed to understand how neuroinflammation may act synergistically with cognitive-decline specific alterations to cause cognitive impairment. PMID:21989322

Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment.

PubMed

VanGuilder, Heather D; Bixler, Georgina V; Brucklacher, Robert M; Farley, Julie A; Yan, Han; Warrington, Junie P; Sonntag, William E; Freeman, Willard M

2011-10-11

Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline. Three independent cohorts of adult (12-13 months) and aged (26-28 months) F344xBN rats were behaviorally characterized by Morris water maze testing. Expression of MHC II pathway-associated genes identified by transcriptomic analysis as upregulated with advanced aging was quantified by qPCR in synaptosomal fractions derived from whole hippocampus and in hippocampal subregion dissections (CA1, CA3, and DG). Activation of astrocytes and microglia was assessed by GFAP and Iba1 protein expression, and by immunohistochemical visualization of GFAP and both CD74 (Ox6) and Iba1. We report a marked age-related induction of neuroinflammatory signaling transcripts (i.e., MHC II components, toll-like receptors, complement, and downstream signaling factors) throughout the hippocampus in all aged rats regardless of cognitive status. Astrocyte and microglial activation was evident in CA1, CA3 and DG of intact and impaired aged rat groups, in the absence of differences in total numbers of GFAP+ astrocytes or Iba1+ microglia. Both mild and moderate microglial activation was significantly increased in all three hippocampal subregions in aged cognitively intact and cognitively impaired rats compared to adults. Neither induction of MHCII pathway gene expression nor glial activation correlated to cognitive performance. These data demonstrate a novel, coordinated age-related induction of the MHC II immune response pathway and glial activation in the hippocampus, indicating an allostatic shift toward a para-inflammatory phenotype with advancing age. Our findings demonstrate that age-related induction of these aspects of hippocampal neuroinflammation, while a potential contributing factor, is not sufficient by itself to elicit impairment of spatial learning and memory in models of normative aging. Future efforts are needed to understand how neuroinflammation may act synergistically with cognitive-decline specific alterations to cause cognitive impairment.

Catecholamine crisis during induction of general anesthesia : A case report.

PubMed

Sonntagbauer, M; Koch, A; Strouhal, U; Zacharowski, K; Weber, C F

2018-03-01

Catecholamine crises associated with pheochromocytoma may cause life-threatening cardiovascular conditions. We report the case of a 75-year-old male who developed a hypertensive crisis during induction of general anesthesia for elective resection of a cervical neuroma due to an undiagnosed pheochromocytoma. Hemodynamic instability occurred immediately after the injection of fentanyl, propofol and rocuronium, prior to laryngoscopy and in the absence of any manipulation of the abdomen. In this case report, we present the management of this incident and discuss the underlying pathophysiology triggering a catecholamine crisis.

Hypoxia promotes luteal cell death in bovine corpus luteum.

PubMed

Nishimura, Ryo; Komiyama, Junichi; Tasaki, Yukari; Acosta, Tomas J; Okuda, Kiyoshi

2008-03-01

Low oxygen caused by a decreasing blood supply is known to induce various responses of cells, including apoptosis. The present study was conducted to examine whether low-oxygen conditions (hypoxia) induce luteal cell apoptosis in cattle. Bovine midluteal cells incubated under hypoxia (3% O(2)) showed significantly more cell death than did those incubated under normoxia (20% O(2)) at 24 and 48 h of culture, and had significantly lower progesterone (P4) levels starting at 8 h. Characteristic features of apoptosis, such as shrunken nuclei and DNA fragmentation, were observed in cells cultured under hypoxia for 48 h. Hypoxia increased the mRNA expressions of BNIP3 and caspase 3 at 24 and 48 h of culture. Hypoxia had no significant effect on the expressions of BCL2 and BAX mRNA. Hypoxia also increased BNIP3 protein, and activated caspase-3. Treatment of P4 attenuated cell death, caspase-3 mRNA expression, and caspase-3 activity under hypoxia. Overall results of the present study indicate that hypoxia induces luteal cell apoptosis by enhancing the expression of proapoptotic protein, BNIP3, and by activating caspase-3, and that the induction of apoptosis by hypoxia is partially caused by a decrease in P4 production. Because hypoxia suppresses P4 synthesis in bovine luteal cells, we suggest that oxygen deficiency caused by a decreasing blood supply in bovine corpus luteum is one of the major factors contributing to both functional and structural luteolysis.

Oil shale processing as a source of aquatic pollution: monitoring of the biologic effects in caged and feral freshwater fish.

PubMed Central

Tuvikene, A; Huuskonen, S; Koponen, K; Ritola, O; Mauer, U; Lindström-Seppä, P

1999-01-01

The biologic effects of the oil shale industry on caged rainbow trout (Oncorhynchus mykiss) as well as on feral perch (Perca fluviatilis) and roach (Rutilus rutilus) were studied in the River Narva in northeast Estonia. The River Narva passes the oil shale mining and processing area and thus receives elevated amounts of polycyclic aromatic hydrocarbons (PAHs), heavy metals, and sulfates. The effects of the chemical load were monitored by measuring cytochrome P4501A (CYP1A)-dependent monooxygenase (MO) activities [7-ethoxyresorufin O-deethylase and aryl hydrocarbon hydroxylase (AHH)] as well as conjugation enzyme activities [glutathione S-transferase (GST) and UDP-glucuronosyltransferase] in the liver of fish. CYP1A induction was further studied by detecting the amount and occurrence of the CYP1A protein. Histopathology of tissues (liver, kidney, spleen, and intestine) and the percentage of micronuclei in fish erythrocytes were also determined. Selected PAHs and heavy metals (Cd, Cu, Hg, and Pb) were measured from fish muscle and liver. In spite of the significant accumulation of PAHs, there was no induction of MO activities in any studied fish species. When compared to reference samples, AHH activities were even decreased in feral fish at some of the exposed sites. Detection of CYP1A protein content and the distribution of the CYP1A enzyme by immunohistochemistry also did not show extensive CYP1A induction. Instead, GST activities were significantly increased at exposed sites. Detection of histopathology did not reveal major changes in the morphology of tissues. The micronucleus test also did not show any evidence of genotoxicity. Thus, from the parameters studied, GST activity was most affected. The lack of catalytic CYP1A induction in spite of the heavy loading of PAHs was not studied but has been attributed to the elevated content of other compounds such as heavy metals, some of which can act as inhibitors for MOs. Another possible explanation of this lack of induction is that through adaptation processes the fish could have lost some of their sensitivity to PAHs. Either complex pollution caused by oil shale processing masked part of the harmful effects measured in this study, or oil shale industry did not have any severe effects on fish in the River Narva. Our study illustrates the difficulties in estimating risk in cases where there are numerous various contaminants affecting the biota. Images Figure 1 Figure 2 PMID:10464075

Induction of fungal disease resistance in Vicia faba by dual inoculation with Rhizobium leguminosarum and vesicular-arbuscular mycorrhizal fungi.

PubMed

Rabie, G H

1998-01-01

Infection of Vicia faba with Bothytis fabae causes significant decreases in growth vigour, total nitrogen content, number of nodules and nutrient accumulation. Na-uptake and phenolics concentration increased compared to that of noninfected plants. In contrast, dual inoculation of Rhizobium and VA mycorrhizae increased all above parameters suggesting a distinct improvement of the plants. The results also revealed that an inverse correlation may exist between phenolic, calcium, magnesium and zinc concentrations in mycorrhizal plant tissues grown in presence of rhizobial bacteria and the disease severity. From these findings we conclude a possible role of both VA mycorrhizal fungi and rhizobial bacteria in the decrease of susceptibility of plants.

Streamed video clips to reduce anxiety in children during inhaled induction of anesthesia.

PubMed

Mifflin, Katherine A; Hackmann, Thomas; Chorney, Jill Maclaren

2012-11-01

Anesthesia induction in children is frequently achieved by inhalation of nitrous oxide and sevoflurane. Pediatric anesthesiologists commonly use distraction techniques such as humor or nonprocedural talk to reduce anxiety and facilitate a smooth transition at this critical phase. There is a large body of successful distraction research that explores the use of video and television distraction methods for minor medical and dental procedures, but little research on the use of this method for ambulatory surgery. In this randomized control trial study we examined whether video distraction is effective in reducing the anxiety of children undergoing inhaled induction before ambulatory surgery. Children (control = 47, video = 42) between 2 and 10 years old undergoing ambulatory surgery were randomly assigned to a video distraction or control group. In the video distraction group a video clip of the child's preference was played during induction, and the control group received traditional distraction methods during induction. The modified Yale Preoperative Anxiety Scale was used to assess the children's anxiety before and during the process of receiving inhalation anesthetics. All subjects were similar in their age and anxiety scores before entering the operating rooms. Children in the video distraction group were significantly less anxious at induction and showed a significantly smaller change in anxiety from holding to induction than did children in the control group. Playing video clips during the inhaled induction of children undergoing ambulatory surgery is an effective method of reducing anxiety. Therefore, pediatric anesthesiologists may consider using video distraction as a useful, valid, alternative strategy for achieving a smooth transition to the anesthetized state.

A potential protective effect of α-tocopherol on vascular complication in spinal cord reperfusion injury in rats

PubMed Central

2010-01-01

Background Paraplegia remains a potential complication of spinal cord ischemic reperfusion injury (IRI) in which oxidative stress induced cyclooxygenase activities may contribute to ischemic neuronal damage. Prolonged administration of vitamin E (α-TOL), as a potent biological antioxidant, may have a protective role in this oxidative inflammatory ischemic cascade to reduce the incidence of paraplegia. The present study was designed to evaluate the preventive value of α-TOL in IRI of spinal cord. Methods For this study, 50 male Sprague-Dawley rats were used and divided into five experimental groups (n = 10): Control group (C); α-TOL control group (CE) which received intramuscular (i.m.) α-TOL injections (600 mg/kg); Sham operated group (S), IRI rats were subjected to laparotomy and clamping of the aorta just above the bifurcation for 45 min, then the clamp was released for 48 hrs for reperfusion; and IRIE rats group, received 600 mg/kg of α-TOL i.m. twice weekly for 6 weeks, followed by induction of IRI similar to the IRI group. At the end of the experimental protocol; motor, sensory and placing/stepping reflex evaluation was done. Plasma nitrite/nitrate (NOx) was measured. Then animals' spinal cord lumbar segments were harvested and homogenized for measurement of the levels of prostaglandin E2 (PGE2), malondialdehyde (MDA) and advanced oxidation products (AOPP), while superoxide dismutase (SOD) and catalase (CAT) activity were evaluated. Results Induction of IRI in rats resulted in significant increases in plasma levels of nitrite/nitrate (p < 0.001) and spinal cord homogenate levels of PGE2, MDA, advanced oxidation protein products AOPP and SOD with significant reduction (p < 0.001) in CAT homogenate levels. Significant impairment of motor, sensory functions and placing/stepping reflex was observed with IRI induction in the spinal cord (p < 0.001). α-TOL administration in IRIE group significantly improved all the previously measured parameters compared with IRI group. Conclusions α-TOL administration significantly prevents the damage caused by spinal cord IRI in rats with subsequent recovery of both motor and sensory functions. Alpha-tocopherol improves the oxidative stress level with subsequent reduction of the incidence of neurological deficits due to spinal cord IRI conditions. PMID:20609232

Comparison of labour induction with misoprostol and dinoprostone and characterization of uterine response based on electrohysterogram.

PubMed

Benalcazar-Parra, Carlos; Monfort-Orti, Rogelio; Ye-Lin, Yiyao; Prats-Boluda, Gema; Alberola-Rubio, Jose; Perales, Alfredo; Garcia-Casado, Javier

2017-12-17

The objective of this study is to compare the uterine activity response between women administered dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for induction of labour (IOL) by analysing not only the traditional obstetric data but also the parameters extracted from uterine electrohysterogram (EHG). Two cohorts were defined: misoprostol (25-µg vaginal tablets; 251 women) and dinoprostone cohort (10 mg vaginal inserts; 249 women). All the mothers were induced by a medical indication of a Bishop Score < = 6. The misoprostol cohort was associated with a shorter time to achieve active labour (p = .017) and vaginal delivery (p = .009) and with a higher percentage of vaginal delivery in less than 24 h in mothers with a very unfavourable cervix score (risk ratio (RR): 1.41, IC95% 1.17-1.69, p = .002). Successful inductions with misoprostol showed EHG parameter values significantly higher than basal state for amplitude and pseudo Montevideo units (PMU) 60' after drug administration, while spectral parameters significantly increased after 150'. This response was not observed in failed inductions. In the successful dinoprostone group, the duration and number of contractions increased significantly after 120', PMU did so after 180', and no significant differences were found for spectral parameters, possibly due to the slower pharmacokinetics of this drug. Successful inductions of labour by misoprostol are associated with earlier effective contractions than in labours induced by dinoprostone.

Topically applied standardized aqueous extract of Curcuma longa Linn. suppresses endotoxin-induced uveal inflammation in rats.

PubMed

Agarwal, Renu; Gupta, S K; Agarwal, Puneet; Srivastava, Sushma

2013-10-01

Aqueous extract of C. longa when administered 4 h after induction of E. coli lipopolysaccharide-induced uveitis in rats showed significantly suppressed inflammation with a significantly lower mean clinical grade, histopathological grade and aqueous humor (AH) protein level compared to vehicle treated group. Although, prednisolone group showed significantly lower clinical grade, histopathological grades and AH protein levels compared to C. longa group, TNF-alpha levels did not differ significantly. Moreover, when the aqueous extract was administered starting from 3 days before induction of uveitis, the mean clinical and histopathological grade as well as AH protein and TNF-alpha levels were comparable to C. longa group when treatment was administered 4 h after induction of uveitis. It is concluded that topically applied standardized aqueous extract of C. longa suppresses endotoxin-induced uveitis in rats by reducing TNF-alpha activity.

Zebrafish pax8 is required for otic placode induction and plays a redundant role with Pax2 genes in the maintenance of the otic placode.

PubMed

Mackereth, Melinda D; Kwak, Su-Jin; Fritz, Andreas; Riley, Bruce B

2005-01-01

Vertebrate Pax2 and Pax8 proteins are closely related transcription factors hypothesized to regulate early aspects of inner ear development. In zebrafish and mouse, Pax8 expression is the earliest known marker of otic induction, and Pax2 homologs are expressed at slightly later stages of placodal development. Analysis of compound mutants has not been reported. To facilitate analysis of zebrafish pax8, we completed sequencing of the entire gene, including the 5' and 3' UTRs. pax8 transcripts undergo complex alternative splicing to generate at least ten distinct isoforms. Two different subclasses of pax8 splice isoforms encode different translation initiation sites. Antisense morpholinos (MOs) were designed to block translation from both start sites, and four additional MOs were designed to target different exon-intron boundaries to block splicing. Injection of MOs, individually and in various combinations, generated similar phenotypes. Otic induction was impaired, and otic vesicles were small. Regional ear markers were expressed correctly, but hair cell production was significantly reduced. This phenotype was strongly enhanced by simultaneously disrupting either of the co-inducers fgf3 or fgf8, or another early regulator, dlx3b, which is thought to act in a parallel pathway. In contrast, the phenotype caused by disrupting foxi1, which is required for pax8 expression, was not enhanced by simultaneously disrupting pax8. Disrupting pax8, pax2a and pax2b did not further impair otic induction relative to loss of pax8 alone. However, the amount of otic tissue gradually decreased in pax8-pax2a-pax2b-deficient embryos such that no otic tissue was detectable by 24 hours post-fertilization. Loss of otic tissue did not correlate with increased cell death, suggesting that otic cells dedifferentiate or redifferentiate as other cell type(s). These data show that pax8 is initially required for normal otic induction, and subsequently pax8, pax2a and pax2b act redundantly to maintain otic fate.

Evaluation of emergence delirium in Asian children using the Pediatric Anesthesia Emergence Delirium Scale.

PubMed

Bong, Choon L; Ng, Agnes S B

2009-06-01

Emergence delirium (ED) is a common problem in children recovering from general anesthesia. ED causes disruption in the postanesthetic care unit, making nursing and monitoring more difficult, and is potentially dangerous to the child. The greatest hindrance to understanding ED was the lack of a standardized tool to assess it. The Pediatric Anesthesia Emergence Delirium (PAED) Scale was recently described to measure the degree of ED in children. In this prospective observational study, we sought to evaluate the incidence of ED by grading emergence behavior using the PAED Score in healthy Asian children undergoing outpatient surgery. Three hundred sixteen children aged 2-12 years undergoing general anesthesia for elective outpatient surgery were included. No premedication was administered. Induction behavior was graded using the induction compliance checklist, and the presence of any excitation on induction documented. Emergence behavior was recorded using the PAED Scale, and the children were separately assessed for clinical agitation. One hundred and thirty-six children (43%) had PAED Scores >0 and 33 (10.4%) had PAED Scores of >or=10. Only 28 children (8.9%) had clinical agitation consistent with ED, the rest were agitated for other reasons. A score of >or=10 on the PAED Scale was the best discriminator between presence and absence of clinical agitation. The area under the receiver operating characteristic curve for PAED Score of >or=10 was 0.98, with a true-positive rate (sensitivity) of 0.85 and a false-positive rate (1-specificity) of 0.041. Four factors were found to be predictive of ED. These include young age, poor compliance at induction, lack of intraoperative fentanyl use and rapid time to awakening. The incidence of ED is approximately 10% in our population of healthy, unpremedicated Asian children undergoing day surgery. Young age, poor compliance at induction, lack of intraoperative fentanyl use and rapid time to awakening were predictive risk factors for ED in our population. A PAED Score of >or=10 was correlated with clinically significant ED and appeared to be the ideal cutoff score for ED.

Ovulation induction by antiestrogens in an Indian tropical vespertillionid bat, Scotophilus heathi.

PubMed

Pakrasi, Pranab Lal; Tiwari, Anjana

2006-11-02

The ovulation induction property of ICI 182,780 a pure antiestrogen and enclomiphene citrate (ENC) was carried out in Scotophilus heathi, an Indian tropical vespertillionid bat, during December to February i.e., preovulatory period. This bat ovulates two ova naturally and shows ovulatory asynchrony. The study showed that 100 ìg of ENC followed by 10 IU hCG resulted in significantly lower number of ovulation. Whereas, the pure antiestrogen ICI 182,780 at a dose of 100 ìg followed by 10 IU hCG resulted in ovulation induction (4.2 +/- 0.4), which is significantly different in comparison to other groups. This is possibly the first report of ovulation induction using this pure antiestrogen i.e., ICI 182,780 in any bat as well as in any animal model that exhibits temporary anovulation similar to polycystic ovary disease (PCOD). This antiestrogen may be useful to induce ovulation in PCOD patients.

Training the elderly on the ability factors of spatial orientation and inductive reasoning.

PubMed

Willis, S L; Schaie, K W

1986-09-01

We examined the effects of cognitive training with elderly participants from the Seattle Longitudinal Study. Subjects were classified as having remained stable or having declined over the previous 14-year interval on each of two primary abilities, spatial orientation and inductive reasoning. Subjects who had declined on one of these abilities received training on that ability; subjects who had declined on both abilities or who had remained stable on both were randomly assigned to the spatial orientation or inductive reasoning training programs. Training outcomes were examined within an ability-measurement framework with empirically determined factorial structure. Significant training effects, at the level of the latent ability constructs, occurred for both spatial orientation and inductive reasoning. These effects were general, in that no significant interactions with decline status or gender were found. Thus, training interventions were effective both in remediating cognitive decline on the target abilities and in improving the performance of stable subjects.

Vibrational excitation in O2and Cl2inductively-coupled plasmas and DC discharges

NASA Astrophysics Data System (ADS)

Booth, Jean-Paul; Marinov, Daniil; Foucher, Mickael; Annusova, Adriana; Guerra, Vasco

2016-09-01

Low-energy electrons can interact with molecules via resonances to cause vibrational excitation with large cross-sections. Such processes can absorb significant energy from the plasma electrons, affecting the electron energy distribution and potentially (via vibration-translation (VT) energy transfer) causing substantial gas heating. The presence of vibrationally excited molecules may significant increase the rates of collisional processes, including electron dissociative attachment and electron impact dissociation into neutral atoms. However, the cross-sections of these processes are often poorly known since they are extremely difficult to measure directly, and reliable theoretical calculations are only now appearing for simple diatomic molecules. We have measured the vibrational distributions in discharges in pure O2 and pure Cl2, using high-sensitivity ultra-broadband ultraviolet absorption spectroscopy. In O2 plasmas significant vibrational excitation is observed, up to v'' =18, with a tail temperature of around 8000K. In Cl2 excitation is only observed up to v'' =3, and the distribution appears to be in local equilibrium with the gas translational temperature (up to 1500K). We are developing a detailed self-consistent 0D global model of these systems including vibrational excitation. Work performed in the LABEX Plas@par project, with financial state aid (ANR-11-IDEX-0004-02 and ANR-13-BS09-0019).

Social exclusion intensifies anxiety-like behavior in adolescent rats.

PubMed

Lee, Hyunchan; Noh, Jihyun

2015-05-01

Social connection reduces the physiological reactivity to stressors, while social exclusion causes emotional distress. Stressful experiences in rats result in the facilitation of aversive memory and induction of anxiety. To determine the effect of social interaction, such as social connection, social exclusion and equality or inequality, on emotional change in adolescent distressed rats, the emotional alteration induced by restraint stress in individual rats following exposure to various social interaction circumstances was examined. Rats were assigned to one of the following groups: all freely moving rats, all rats restrained, rats restrained in the presence of freely moving rats and freely moving rats with a restrained rat. No significant difference in fear-memory and sucrose consumption between all groups was found. Change in body weight significantly increased in freely moving rats with a restrained rat, suggesting that those rats seems to share the stressful experience of the restrained rat. Interestingly, examination of the anxiety-like behavior revealed only rats restrained in the presence of freely moving rats to have a significant increase, suggesting that emotional distress intensifies in positions of social exclusion. These results demonstrate that unequally excluded social interaction circumstances could cause the amplification of distressed status and anxiety-related emotional alteration. Copyright © 2015 Elsevier B.V. All rights reserved.

Radiation induction of drug resistance in RIF-1: Correlation of tumor and cell culture results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moulder, J.E.; Hopwood, L.E.; Volk, D.M.

1991-02-01

The RIF-1 tumor line contains cells that are resistant to various anti-neoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), adriamycin (ADR), and etoposide (VP16). The frequency of these drug-resistant cells is increased after irradiation. The frequency of drug-resistant cells and the magnitude of radiation-induced drug resistance are different in cell culture than in tumors. The dose-response and expression time relationships for radiation induction of drug resistance observed in RIF-1 tumors are unusual.We hypothesize that at high radiation doses in vivo, we are selecting for cells that are both drug resistant and radiation resistant due to microenvironmental factors, whereas at low radiationmore » doses in vivo and all radiation doses in vitro, we are observing true mutants. These studies indicate that there can be significant differences in drug-resistance frequencies between tumors and their cell lines of origin, and that radiation induction of drug resistance depends significantly on whether the induction is done in tumors or in cell culture. These results imply that theories about the induction of drug resistance that are based on cell culture studies may be inapplicable to the induction of drug resistance in tumors.« less

Tobacco smoke induces epithelial barrier dysfunction via receptor EphA2 signaling.

PubMed

Nasreen, Najmunnisa; Khodayari, Nazli; Sriram, Peruvemba S; Patel, Jawaharlal; Mohammed, Kamal A

2014-06-15

Erythropoietin-producing human hepatocellular carcinoma (Eph) receptors are the largest family of receptor tyrosine kinases (RTKs) that mediate various cellular and developmental processes. The degrees of expression of these key molecules control the cell-cell interactions. Although the role of Eph receptors and their ligand Ephrins is well studied in developmental processes, their function in tobacco smoke (TS)-induced epithelial barrier dysfunction is unknown. We hypothesized that TS may induce permeability in bronchial airway epithelial cell (BAEpC) monolayer by modulating receptor EphA2 expression, actin cytoskeleton, adherens junction, and focal adhesion proteins. Here we report that in BAEpCs, acute TS exposure significantly upregulated EphA2 and EphrinA1 expression, disrupted the actin filaments, decreased E-cadherin expression, and increased protein permeability, whereas the focal adhesion protein paxillin was unaffected. Silencing the receptor EphA2 expression with silencing interference RNA (siRNA) significantly attenuated TS-induced hyperpermeability in BAEpCs. In addition, when BAEpC monolayer was transfected with EphA2-expressing plasmid and treated with recombinant EphrinA1, the transepithelial electrical resistance decreased significantly. Furthermore, TS downregulated E-cadherin expression and induced hyperpermeability across BAEpC monolayer in a Erk1/Erk2, p38, and JNK MAPK-dependent manner. TS induced hyperpermeability in BAEpC monolayer by targeting cell-cell adhesions, and interestingly cell-matrix adhesions were unaffected. The present data suggest that TS causes significant damage to the BAEpCs via induction of EphA2 and downregulation of E-cadherin. Induction of EphA2 in the BAEpCs exposed to TS may be an important signaling event in the pathogenesis of TS-induced epithelial injury.

Thyroid Hormone Regulates the Expression of the Sonic Hedgehog Signaling Pathway in the Embryonic and Adult Mammalian Brain

PubMed Central

Desouza, Lynette A.; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E.; Kottmann, Andreas H.; Tole, Shubha

2011-01-01

Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and hyperthyroidism bidirectionally influenced Shh mRNA in embryonic forebrain signaling centers at stages before fetal thyroid hormone synthesis. Further, Smo and Ptc expression were significantly decreased in the forebrain of embryos derived from hypothyroid dams. Adult-onset thyroid hormone perturbations also regulated expression of the Shh pathway bidirectionally, with a significant induction of Shh, Ptc, and Smo after hyperthyroidism and a decline in Smo expression in the hypothyroid brain. Short-term T3 administration resulted in a significant induction of cortical Shh mRNA expression and also enhanced reporter gene expression in Shh+/LacZ mice. Further, acute T3 treatment of cortical neuronal cultures resulted in a rapid and significant increase in Shh mRNA, suggesting direct effects. Chromatin immunoprecipitation assays performed on adult neocortex indicated enhanced histone acetylation at the Shh promoter after acute T3 administration, providing further support that Shh is a thyroid hormone-responsive gene. Our results indicate that maternal and adult-onset perturbations of euthyroid status cause robust and region-specific changes in the Shh pathway in the embryonic and adult forebrain, implicating Shh as a possible mechanistic link for specific neurodevelopmental effects of thyroid hormone. PMID:21363934

Impact of type of calcineurin inhibitor on post-transplant tuberculosis: Single-center study from India.

PubMed

Agarwal, Sanjay K; Bhowmik, Dipankar; Mahajan, Sandeep; Bagchi, Soumita

2017-02-01

Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipients. Immunosuppressive drugs are one of the most important risk factor for post-transplant tuberculosis (PTTB). A paucity of data exists about the impact of the type of calcineurin inhibitor on PTTB. In this retrospective study, all adult patients on calcineurin inhibitor-based immunosuppression were included. Patients receiving TB chemoprophylaxis were excluded. Diabetes, duration of dialysis, hepatitis B and C, past treated TB, induction therapy, type of antimetabolite, acute rejection, new onset of diabetes after renal transplantation (RT) (NODAT) and cytomegalovirus (CMV) were analyzed in tacrolimus (Tac) and cyclosporine (CsA) groups. Primary outcome was incidence of TB and secondary outcomes were timeline of development of TB after RT and pattern of TB in the two groups. Of the 1664 patients included, 582 patients received CsA-based immunosuppression while 1082 received Tac-based immunosuppression. Duration of dialysis, positive tuberculin skin test, use of induction, mycophenolate mofetil use, CMV infection, and NODAT were significantly more, and hepatitis B infection, past treated TB, and acute rejection episodes were significantly less in the Tac group. At the end of follow-up, incidence of TB in the Tac group was significantly less than in the CsA group (6.1% vs 19.9%, P<.001). Mean time for development of TB after RT was similar in both the groups and nodal and disseminated TB were more common in the Tac group. In conclusion, our study shows that use of Tac as compared to CsA significantly decreases incidence of PTTB. Time of infection since transplant was similar in both the groups. However, nodal and disseminated TB were more common in the Tac group. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fumonisin exposure in women linked to inhibition of an enzyme that is a key event in farm and laboratory animal diseases.

USDA-ARS?s Scientific Manuscript database

Fumonisin B1 (FB1) is a toxic chemical produced by molds. The molds that produce fumonisin are common in corn. Consumption of contaminated corn by farm animals has been shown to be the cause of animal disease. The proximate cause (key event) in the induction of diseases in animals is inhibition of t...

Impact of cladribine therapy on changes in circulating dendritic cell subsets, T cells and B cells in patients with multiple sclerosis.

PubMed

Mitosek-Szewczyk, Krystyna; Tabarkiewicz, Jacek; Wilczynska, Barbara; Lobejko, Katarzyna; Berbecki, Jerzy; Nastaj, Marcin; Dworzanska, Ewa; Kolodziejczyk, Beata; Stelmasiak, Zbigniew; Rolinski, Jacek

2013-09-15

Cladribine causes sustained reduction in peripheral T and B cell populations while sparing other immune cells. We determined two populations of dendritic cells (DCs): namely CD1c(+)/CD19(-) (myeloid DCs) and CD303(+)/CD123(+) (plasmacytoid DCs), CD19(+) B lymphocytes, CD3(+) T lymphocytes and CD4(+) or CD8(+) subpopulations in patients with multiple sclerosis after cladribine therapy. We examined 50 patients with secondary progressive multiple sclerosis (SP MS) according to McDonalds et al.'s criteria, 2001 [15]. Blood samples were collected before the initiation of cladribine therapy and after 1st, 2nd, 3th, 4th and 5th courses of treatment. DC subsets, T and B cells were analyzed by flow cytometry. During cladribine treatment the myeloid DCs CD1c(+)/CD19(-) did not change (p=0.73175), and the plasmacytoid DCs CD303(+)/CD123(+) significantly increased (p=0.00034) which resulted in significant changes in the ratio of myeloid DCs to plasmacytoid DCs (p=0.00273). During therapy, B lymphocyte CD19(+) significantly decreased (p=0.00005) and significant changes in CD4(+) cells (p=0.00191), changes in CD8(+) cells (p=0.05760) and significant changes in CD3(+) (p=0.01822) were found. We noticed significant trend to increase the CD303(+) circulating the dendritic cells. This population produces large amounts of IFN-alfa. We found significant and rapid decrease in B cells and CD4(+) Th cells. Our results suggest two possible ways of beneficial cladribine influence on immune system in MS. Induction of IFN-alfa producing cells and their predominance over BDCA-1(+) DCs, which are associated with cytotoxic response. Additionally, cladribine could influence two populations of lymphocytes: B cells and Th lymphocytes responsible for induction of immune response against myelin antigens. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of carprofen on renal function during medetomidine-propofol-isoflurane anesthesia in dogs.

PubMed

Frendin, Jan H M; Boström, Ingrid M; Kampa, Naruepon; Eksell, Per; Häggström, Jens U; Nyman, Görel C

2006-12-01

To investigate effects of carprofen on indices of renal function and results of serum bio-chemical analyses and effects on cardiovascular variables during medetomidine-propofol-isoflurane anesthesia in dogs. 8 healthy male Beagles. A randomized crossover study was conducted with treatments including saline (0.9% NaCl) solution (0.08 mL/kg) and carprofen (4 mg/kg) administered IV. Saline solution or carprofen was administered 30 minutes before induction of anesthesia and immediately before administration of medetomidine (20 microg/kg, IM). Anesthesia was induced with propofol and maintained with inspired isoflurane in oxygen. Blood gas concentrations and ventilation were measured. Cardiovascular variables were continuously monitored via pulse contour cardiac output (CO) measurement. Renal function was assessed via glomerular filtration rate (GFR), renal blood flow (RBF), scintigraphy, serum biochemical analyses, urinalysis, and continuous CO measurements. Hematologic analysis was performed. Values did not differ significantly between the carprofen and saline solution groups. For both treatments, sedation and anesthesia caused changes in results of serum biochemical and hematologic analyses; a transient, significant increase in urine alkaline phosphatase activity; and blood flow diversion to the kidneys. The GFR increased significantly in both groups despite decreased CO, mean arterial pressure, and absolute RBF variables during anesthesia. Carprofen administered IV before anesthesia did not cause detectable, significant adverse effects on renal function during medetomidine-propofol-isoflurane anesthesia in healthy Beagles.

Evaluation of Pentafluoroethane and 1,1-Difluoroethane for a Dielectric Etch Application in an Inductively Coupled Plasma Etch Tool

NASA Astrophysics Data System (ADS)

Karecki, Simon; Chatterjee, Ritwik; Pruette, Laura; Reif, Rafael; Sparks, Terry; Beu, Laurie; Vartanian, Victor

2000-07-01

In this work, a combination of two hydrofluorocarbon compounds, pentafluoroethane (FC-125, C2HF5) and 1,1-difluoroethane (FC-152a, CF2H-CH3), was evaluated as a potential replacement for perfluorocompounds in dielectric etch applications. A high aspect ratio oxide via etch was used as the test vehicle for this study, which was conducted in a commercial inductively coupled high density plasma etch tool. Both process and emissions data were collected and compared to those provided by a process utilizing a standard perfluorinated etch chemistry (C2F6). Global warming (CF4, C2F6, CHF3) and hygroscopic gas (HF, SiF4) emissions were characterized using Fourier transform infrared (FTIR) spectroscopy. FC-125/FC-152a was found to produce significant reductions in global warming emissions, on the order of 68 to 76% relative to the reference process. Although etch stopping, caused by a high degree of polymer deposition inside the etched features, was observed, process data otherwise appeared promising for an initial study, with good resist selectivity and etch rates being achieved.

Inducers of Glycinebetaine Synthesis in Barley1

PubMed Central

Jagendorf, André T.; Takabe, Tetsuko

2001-01-01

Glycinebetaine is an osmoprotectant accumulated by barley (Hordeum vulgare) plants in response to high levels of NaCl, drought, and cold stress. Using barley seedlings in hydroponic culture, we characterized additional inducers of glycinebetaine accumulation. These included other inorganic salts (KCl, MgCl2, LiCl, and Na2SO4), oxidants (H2O2 and cumene hydroperoxide), and organic compounds (abscisic acid, polymixin B, n-butanol, salicylic acid, and aspirin). Stress symptoms brought on by high NaCl and other inducers, and not necessarily correlated with glycinebetaine accumulation, include wilting, loss of chlorophyll, and increase in thiobarbituric acid reacting substances. For NaCl, Ca2+ ions at 10 to 20 mm decrease these stress symptoms without diminishing, or even increasing, glycinebetaine induction. Abscisic acid induces glycinebetaine accumulation without causing any of the stress symptoms. NaCl, KCl, and H2O2 (but not other inducers) induce glycinebetaine at concentrations below those needed for the other stress symptoms. Mg2+ at 10 to 20 mm induces both stress symptoms and glycinebetaine, but only at low (0.2 mm) Ca2+. Although illumination is needed for optimal induction, a significant increase in the leaf glycinebetaine level is found in complete darkness, also. PMID:11743126

Induction of calcium-dependent nitric oxide synthases by sex hormones.

PubMed

Weiner, C P; Lizasoain, I; Baylis, S A; Knowles, R G; Charles, I G; Moncada, S

1994-05-24

We have examined the effects of pregnancy and sex hormones on calcium-dependent and calcium-independent nitric oxide synthases (NOSs) in the guinea pig. Pregnancy (near term) caused a > 4-fold increase in the activity of calcium-dependent NOS in the uterine artery and at least a doubling in the heart, kidney, skeletal muscle, esophagus, and cerebellum. The increase in NOS activity in the cerebellum during pregnancy was inhibited by the estrogen-receptor antagonist tamoxifen. Treatment with estradiol (but not progesterone) also increased calcium-dependent NOS activity in the tissues examined from both females and males. Testosterone increased calcium-dependent NOS only in the cerebellum. No significant change in calcium-independent NOS activity was observed either during pregnancy or after the administration of any sex hormone. Both pregnancy and estradiol treatment increased the amount of mRNAs for NOS isozymes eNOS and nNOS in skeletal muscle, suggesting that the increases in NOS activity result from enzyme induction. Thus both eNOS and nNOS are subject to regulation by estrogen, an action that could explain some of the changes that occur during pregnancy and some gender differences in physiology and pathophysiology.

Induction of human umbilical Wharton's jelly-derived mesenchymal stem cells toward motor neuron-like cells.

PubMed

Bagher, Zohreh; Ebrahimi-Barough, Somayeh; Azami, Mahmoud; Mirzadeh, Hamid; Soleimani, Mansooreh; Ai, Jafar; Nourani, Mohammad Reza; Joghataei, Mohammad Taghi

2015-10-01

The most important property of stem cells from different sources is the capacity to differentiate into various cells and tissue types. However, problems including contamination, normal karyotype, and ethical issues cause many limitations in obtaining and using these cells from different sources. The cells in Wharton's jelly region of umbilical cord represent a pool source of primitive cells with properties of mesenchymal stem cells (MSCs). The aim of this study was to determine the potential of human Wharton's jelly-derived mesenchymal stem cells (WJMSCs) for differentiation to motor neuron cells. WJMSCs were induced to differentiate into motor neuron-like cells by using different signaling molecules and neurotrophic factors in vitro. Differentiated neurons were then characterized for expression of motor neuron markers including nestin, PAX6, NF-H, Islet 1, HB9, and choline acetyl transferase (ChAT) by quantitative reverse transcription PCR and immunocytochemistry. Our results showed that differentiated WJMSCs could significantly express motor neuron biomarkers in RNA and protein levels 15 d post induction. These results suggested that WJMSCs can differentiate to motor neuron-like cells and might provide a potential source in cell therapy for neurodegenerative disease.

Regulation of Intracellular Copper by Induction of Endogenous Metallothioneins Improves the Disease Course in a Mouse Model of Amyotrophic Lateral Sclerosis.

PubMed

Tokuda, Eiichi; Watanabe, Shunsuke; Okawa, Eriko; Ono, Shin-ichi

2015-04-01

Mutations in SOD1 cause amyotrophic lateral sclerosis (ALS), an incurable motor neuron disease. The pathogenesis of the disease is poorly understood, but intracellular copper dyshomeostasis has been implicated as a key process in the disease. We recently observed that metallothioneins (MTs) are an excellent target for the modification of copper dyshomeostasis in a mouse model of ALS (SOD1(G93A)). Here, we offer a therapeutic strategy designed to increase the level of endogenous MTs. The upregulation of endogenous MTs by dexamethasone, a synthetic glucocorticoid, significantly improved the disease course and rescued motor neurons in SOD1(G93A) mice, even if the induction was initiated when peak body weight had decreased by 10%. Neuroprotection was associated with the normalization of copper dyshomeostasis, as well as with decreased levels of SOD1(G93A) aggregates. Importantly, these benefits were clearly mediated in a MT-dependent manner, as dexamethasone did not provide any protection when endogenous MTs were abolished from SOD1(G93A) mice. In conclusion, the upregulation of endogenous MTs represents a promising strategy for the treatment of ALS linked to mutant SOD1.

The Underestimated Significance of Conditioning in Placebo Hypoalgesia and Nocebo Hyperalgesia

PubMed Central

Witthöft, Michael

2018-01-01

Placebo and nocebo effects are intriguing phenomena in pain perception with important implications for clinical research and practice because they can alleviate or increase pain. According to current theoretical accounts, these effects can be shaped by verbal suggestions, social observational learning, and classical conditioning and are necessarily mediated by explicit expectation. In this review, we focus on the contribution of conditioning in the induction of placebo hypoalgesia and nocebo hyperalgesia and present accumulating evidence that conditioning independent from explicit expectation can cause these effects. Especially studies using subliminal stimulus presentation and implicit conditioning (i.e., without contingency awareness) that bypass the development of explicit expectation suggest that conditioning without explicit expectation can lead to placebo and nocebo effects in pain perception. Because only few studies have investigated clinical samples, the picture seems less clear when it comes to patient populations with chronic pain. However, conditioning appears to be a promising means to optimize treatment. In order to get a better insight into the mechanisms of placebo and nocebo effects in pain and the possible benefits of conditioning compared to explicit expectation, future studies should carefully distinguish both methods of induction. PMID:29670678

Anxiety, not anger, induces inflammatory activity: An avoidance/approach model of immune system activation.

PubMed

Moons, Wesley G; Shields, Grant S

2015-08-01

Psychological stressors reliably trigger systemic inflammatory activity as indexed by levels of proinflammatory cytokines. This experiment demonstrates that one's specific emotional reaction to a stressor may be a significant determinant of whether an inflammatory reaction occurs in response to that stressor. Based on extant correlational evidence and theory, a causal approach was used to determine whether an avoidant emotion (anxiety) triggers more inflammatory activity than an approach emotion (anger). In an experimental design (N = 40), a 3-way Emotion Condition × Time × Analyte interaction revealed that a writing-based anxiety induction, but not a writing-based anger induction, increased mean levels of interferon-γ (IFN- γ) and interleukin-1β (IL-1β), but not interleukin-6 (IL-6) in oral mucous, F(2, 54) = 4.64, p = .01, ηp(²) = .15. Further, self-reported state anxiety predicted elevated levels of proinflammatory cytokines, all ΔR(²) >.06, ps <.04, but self-reported state anger did not. These results constitute the first evidence to our knowledge that specific negative emotions can differentially cause inflammatory activity and support a theoretical model explaining these effects based on the avoidance or approach motivations associated with emotions. (c) 2015 APA, all rights reserved).

Genetic manipulation of carotenoid biosynthesis and photoprotection.

PubMed

Pogson, B J; Rissler, H M

2000-10-29

There are multiple complementary and redundant mechanisms to provide protection against photo-oxidative damage, including non-photochemical quenching (NPQ). NPQ dissipates excess excitation energy as heat by using xanthophylls in combination with changes to the light-harvesting complex (LHC) antenna. The xanthophylls are oxygenated carotenoids that in addition to contributing to NPQ can quench singlet or triplet chlorophyll and are necessary for the assembly and stability of the antenna. We have genetically manipulated the expression of the epsilon-cyclase and beta-carotene hydroxylase carotenoid biosynthetic enzymes in Arabidopsis thaliana. The epsilon-cyclase overexpression confirmed that lut2 (lutein deficient) is a mutation in the epsilon-cyclase gene and demonstrated that lutein content can be altered at the level of mRNA abundance with levels ranging from 0 to 180% of wild-type. Also, it is clear that lutein affects the induction and extent of NPQ. The deleterious effects of lutein deficiency on NPQ in Arabidopsis and Chlamydomonas are additive, no matter what the genetic background, whether npq1 (zeaxanthin deficient), aba1 or antisense beta-hydroxylase (xanthophyll cycle pool decreased). Additionally, increasing lutein content causes a marginal, but significant, increase in the rate of induction of NPQ despite a reduction in the xanthophyll cycle pool size.

Genetic manipulation of carotenoid biosynthesis and photoprotection.

PubMed Central

Pogson, B J; Rissler, H M

2000-01-01

There are multiple complementary and redundant mechanisms to provide protection against photo-oxidative damage, including non-photochemical quenching (NPQ). NPQ dissipates excess excitation energy as heat by using xanthophylls in combination with changes to the light-harvesting complex (LHC) antenna. The xanthophylls are oxygenated carotenoids that in addition to contributing to NPQ can quench singlet or triplet chlorophyll and are necessary for the assembly and stability of the antenna. We have genetically manipulated the expression of the epsilon-cyclase and beta-carotene hydroxylase carotenoid biosynthetic enzymes in Arabidopsis thaliana. The epsilon-cyclase overexpression confirmed that lut2 (lutein deficient) is a mutation in the epsilon-cyclase gene and demonstrated that lutein content can be altered at the level of mRNA abundance with levels ranging from 0 to 180% of wild-type. Also, it is clear that lutein affects the induction and extent of NPQ. The deleterious effects of lutein deficiency on NPQ in Arabidopsis and Chlamydomonas are additive, no matter what the genetic background, whether npq1 (zeaxanthin deficient), aba1 or antisense beta-hydroxylase (xanthophyll cycle pool decreased). Additionally, increasing lutein content causes a marginal, but significant, increase in the rate of induction of NPQ despite a reduction in the xanthophyll cycle pool size. PMID:11127994

Changes in p53 expression in mouse fibroblasts can modify motility and extracellular matrix organization.

PubMed

Alexandrova, A; Ivanov, A; Chumakov, P; Kopnin, B; Vasiliev, J

2000-11-23

Effects of p53 expression on cell morphology and motility were studied using the derivatives of p53-null 10(1) mouse fibroblasts with tetracycline-regulated expression of exogenous human p53. Induction of p53 expression was accompanied by significant decrease in extracellular matrix (fibronectin) and reduction of matrix fibrils, diminution of the number and size of focal contacts, decrease of cell areas, establishment of more elongated cell shape and alterations of actin cytoskeleton (actin bundles became thinner, their number and size decreased). Expression of His175 and Gln22/ Ser23 p53 mutants caused no such effects. To study the influence of p53 expression on cell motility we used wound technique and videomicroscopy observation of single living cells. It was found that induction of p53 expression led to increase of lamellar activity of cell edge. However, in spite of enhanced lamellar activity p53-expressing cells migrated to shorter distance and filled the narrow wound in longer time as compared with their p53-null counterparts. Possible mechanisms of the influence of p53 expression on cell morphology and motility are discussed.

EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism.

PubMed

Adams, Brian K; Cai, Jiyang; Armstrong, Jeff; Herold, Marike; Lu, Yang J; Sun, Aiming; Snyder, James P; Liotta, Dennis C; Jones, Dean P; Shoji, Mamoru

2005-03-01

In this study, we show that the novel synthetic curcumin analog, EF24, induces cell cycle arrest and apoptosis by means of a redox-dependent mechanism in MDA-MB-231 human breast cancer cells and DU-145 human prostate cancer cells. Cell cycle analysis demonstrated that EF24 causes a G2/M arrest in both cell lines, and that this cell cycle arrest is followed by the induction of apoptosis as evidenced by caspase-3 activation, phosphatidylserine externalization and an increased number of cells with a sub-G1 DNA fraction. In addition, we demonstrate that EF24 induces a depolarization of the mitochondrial membrane potential, suggesting that the compound may also induce apoptosis by altering mitochondrial function. EF24, like curcumin, serves as a Michael acceptor reacting with glutathione (GSH) and thioredoxin 1. Reaction of EF24 with these agents in vivo significantly reduced intracellular GSH as well as oxidized GSH in both the wild-type and Bcl-xL overexpressing HT29 human colon cancer cells. We therefore propose that the anticancer effect of a novel curcumin analog, EF24, is mediated in part by redox-mediated induction of apoptosis.

Inflammasome and Fas-Mediated IL-1β Contributes to Th17/Th1 Cell Induction in Pathogenic Bacterial Infection In Vivo.

PubMed

Uchiyama, Ryosuke; Yonehara, Shin; Taniguchi, Shun'ichiro; Ishido, Satoshi; Ishii, Ken J; Tsutsui, Hiroko

2017-08-01

CD4 + Th cells play crucial roles in orchestrating immune responses against pathogenic microbes, after differentiating into effector subsets. Recent research has revealed the importance of IFN-γ and IL-17 double-producing CD4 + Th cells, termed Th17/Th1 cells, in the induction of autoimmune and inflammatory diseases. In addition, Th17/Th1 cells are involved in the regulation of infection caused by the intracellular bacterium Mycobacterium tuberculosis in humans. However, the precise mechanism of Th17/Th1 induction during pathogen infection is unclear. In this study, we showed that the inflammasome and Fas-dependent IL-1β induces Th17/Th1 cells in mice, in response to infection with the pathogenic intracellular bacterium Listeria monocytogenes In the spleens of infected wild-type mice, Th17/Th1 cells were induced, and expressed T-bet and Rorγt. In Pycard -/- mice, which lack the adaptor molecule of the inflammasome (apoptosis-associated speck-like protein containing a caspase recruitment domain), Th17/Th1 induction was abolished. In addition, the Fas-mediated IL-1β production was required for Th17/Th1 induction during bacterial infection: Th17/Th1 induction was abolished in Fas -/- mice, whereas supplementation with recombinant IL-1β restored Th17/Th1 induction via IL-1 receptor 1 (IL-1R1), and rescued the mortality of Fas -/- mice infected with Listeria IL-1R1, but not apoptosis-associated speck-like protein containing a caspase recruitment domain or Fas on T cells, was required for Th17/Th1 induction, indicating that IL-1β stimulates IL-1R1 on T cells for Th17/Th1 induction. These results indicate that IL-1β, produced by the inflammasome and Fas-dependent mechanisms, contributes cooperatively to the Th17/Th1 induction during bacterial infection. This study provides a deeper understanding of the molecular mechanisms underlying Th17/Th1 induction during pathogenic microbial infections in vivo. Copyright © 2017 by The American Association of Immunologists, Inc.

The effects of local anaesthetic solution in the navicular bursa of horses with lameness caused by distal interphalangeal joint pain.

PubMed

Schumacher, John; Schumacher, Jim; Gillette, R; DeGraves, F; Schramme, M; Smith, R; Perkins, J; Coker, M

2003-07-01

Analgesia of the palmar digital (PD) nerves has been demonstrated to cause analgesia of the distal interphalangeal (DIP) joint as well as the sole. Because the PD nerves lie in close proximity to the navicular bursa, we suspected that that analgesia of the navicular bursa would anaesthetise the PD nerves, which would result in analgesia of the DIP joint. To determine the response of horses with pain in the DIP joint to instillation of local anaesthetic solution into the navicular bursa. Lameness was induced in 6 horses by creating painful synovitis in the DIP joint of one forefoot by administering endotoxin into the joint. Horses were videorecorded while trotting, before and after induction of lameness, at three 10 min intervals after instilling 3.5 ml local anaesthetic solution into the navicular bursa and, finally, after instilling 6 ml solution into the DIP joint. Lameness scores were assigned by grading the videorecorded gaits subjectively. At the 10 and -20 min observations, median lameness scores were not significantly different from those before administration of local anaesthetic solution into the navicular bursa (P > or = 0.05), although lameness scores of 3 of 6 horses improved during this period, and the 20 min observation scores tended toward significance (P = 0.07). At the 30 min observation, and after analgesia of the DIP joint, median lameness scores were significantly improved (P < or = 0.05). These results indicate that pain arising from the DIP joint can probably be excluded as a cause of lameness, when lameness is attenuated within 10 mins by analgesia of the navicular bursa. Pain arising from the DIP joint cannot be excluded as a cause of lameness when lameness is attenuated after 20 mins after analgesia of the navicular bursa.

[Effect of external abdominal aorta compression on circulation during anesthesia induction in elderly patients].

PubMed

Li, Xiuman; Wang, Lixiang

2017-07-01

To investigate the effect of external abdominal aorta compression on circulation during anesthetic induction in elderly patients. A prospective randomized controlled trial was conducted. Patients with age of 60-75 years old, requiring a general anesthesia for non-abdominal surgery, and with II-III class of American Society of Anesthesiologists (ASA) physical status classification, and admitted to General Hospital of Chinese People's Armed Police Forces from January to April in 2017 were enrolled. They were divided into abdominal aorta pressure group and control group according to random number method, with 20 patients in each group. In both groups, anesthesia was induced with midazolam, propofol, fentanyl and cisatracurium, and was maintained with propofol, remifentanil and cisatracurium. After successful intubation, the anesthesia machine was changed into mechanical ventilation. The patients in abdominal aorta pressure group were given abdominal aorta pressure 1 minute after induction of general anesthesia with midazolam till 5 minutes after intubation. The mean arterial pressure (MAP), heart rate (HR) and blood oxygen saturation (SpO 2 ) were observed before anesthesia induction, immediately after anesthesia induction, immediately after intubation, 5 minutes and 10 minutes after intubation, respectively. The incidence of hypotension or bradycardia, and usage of ephedrine or atropine were recorded. There were no significant differences in MAP [mmHg (1 mmHg = 0.133 kPa): 83.6±4.7 vs. 82.9±4.7], HR (bpm: 67.3±5.9 vs. 65.9±5.7) and SpO 2 (0.962±0.007 vs. 0.960±0.009) before anesthesia induction between abdominal aorta pressure group and control group (all P > 0.05). Immediately after anesthesia induction, the MAP and HR in control group were significantly decreased as compared with those before anesthesia induction [MAP (mmHg): 70.0±8.7 vs. 82.9±4.7, HR (bpm): 60.7±6.7 vs. 65.9±5.7, both P < 0.05], and they were also significantly lower than those of abdominal aorta pressure group [MAP (mmHg): 83.1±3.9, HR (bpm): 66.8±4.9, both P < 0.05]. Immediately after intubation, the MAP and HR in control group were significantly increased as compared with those immediately after anesthesia induction [MAP (mmHg): 78.9±7.9 vs. 70.0±8.7, HR (bpm): 67.3±2.7 vs. 60.7±6.7, both P < 0.05], but the changes in MAP and HR in abdominal aorta pressure group were not obvious. During the anesthesia induction period, there was no statistical difference in SpO 2 change between the two groups. During induction of anesthesia, no adverse reaction was found in the abdominal aorta pressure group, but 4 patients with hypotension and 2 patients with bradycardia were found in the control group. Two patients with hypotension were treated with ephedrine, and 2 patients with bradycardia were treated with atropine. Anesthesia induction of elderly patients with abdominal aorta pressure can help maintain hemodynamic stability.

Patient-Perceived Pressure from Clinicians for Labor Induction and Cesarean Delivery: A Population-Based Survey of U.S. Women

PubMed Central

Jou, Judy; Kozhimannil, Katy B; Johnson, Pamela Jo; Sakala, Carol

2015-01-01

Objective To determine whether patient-perceived pressure from clinicians for labor induction or cesarean delivery is significantly associated with having these procedures. Data Sources/Study Setting Listening to Mothers III, a nationally representative survey of women 18–45 years who delivered a singleton infant in a U.S. hospital July 2011–June 2012 (N = 2,400). Study Design Multivariate logistic regression analysis of factors associated with perceived pressure and estimation of odds of induction and cesarean given perceived pressure. Principal Findings Overall, 14.8 percent of respondents perceived pressure from a clinician for labor induction and 13.3 percent for cesarean delivery. Women who perceived pressure for labor induction had higher odds of induction overall (adjusted odds ratio [aOR]: 3.51; 95 percent confidence interval [CI]: 2.5–5.0) and without medical reason (aOR: 2.13; 95 percent CI: 1.3–3.4) compared with women who did not perceive pressure. Those perceiving pressure for cesarean delivery had higher odds of cesarean overall (aOR: 5.17; 95 percent CI: 3.2–8.4), without medical reason (aOR: 6.13; 95 percent CI: 3.4–11.1), and unplanned cesarean (aOR: 6.70; 95 percent CI: 4.0–11.3). Conclusions Patient-perceived pressure from clinicians significantly predicts labor induction and cesarean delivery. Efforts to reduce provider–patient miscommunication and minimize potentially unnecessary procedures may be warranted. PMID:25250981

Thermal and vibration dynamic analysis of an induction motor using optical fiber Bragg gratings

NASA Astrophysics Data System (ADS)

Sousa, Kleiton d. M.; Dreyer, Uilian J.; Martelli, Cicero; Cardozo da Silva, Jean Carlos

2015-09-01

In this paper it is presented the results of temperature and vibration measurements in a Three-phase Induction Motor (TIM) running at no-load condition. Vibration and temperature analysis are the most successful techniques used for condition monitoring of induction motors. The vibration is measured using two FBGs installed inside of the motor between two subsequent stator teeth. The motor spectrum of vibration when power is at 60 Hz presents the frequencies 60 Hz, 120 Hz, 180 Hz, and 240 Hz as theoretically expected. For the temperature measurement two FBGs are encapsulated in an alumina tube fixed along the stator. The results show 0.9°C difference between the two FBG caused by the motor ventilation nearer of one FBG. These measurements can be used to determine TIM parameters and still be predictive maintenance tool.

Influence ofArtemisia princeps var.orientalis components on callus induction and growth.

PubMed

Kil, B S; Yun, K W; Lee, S Y

1992-08-01

An in vitro study was performed to determine the potential application of tissue culture in determining allelopathic potentialof Artemisia princeps var.Orientalis (wormwood). Aqueous extracts and volatile substances ofA. princeps var.Orientalis were tested to determine their effects on callus induction and growth of several tested species. Extracts of 5%A. princeps var.Orientalis caused some reduction in concentration, induction, and growth of callus, although they looked normal, whereas the expiants of most receptor plants did not develop callus at higher concentration. Lettuce andEclipta prostrata were the most sensitive species, andA. princeps var.Orientalis was affected by its own extracts. The growth of calluses in MS 121 medium treated with essential oil ofA. princeps var.Orientalis was inhibited, and the degree of inhibition was proportional to the concentration of the essential oil.